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36,800,717 | Association of Hepcidin levels in Type 2 Diabetes Mellitus treated with metformin or combined anti-diabetic agents in Pakistani population. | To evaluate the impact of hepcidin and ferritin in pathogenesis and prognosis of type 2 diabetes mellitus subjects taking only metformin or combined anti-glycaemic agents. The observational case-control study was conducted at the Department of Physiology, Baqai Medical University, Karachi, from August 2019 to October 2020, and comprised subjects from both genders who categorised into equal groups as non-diabetic controls, newly-diagnosed type 2 diabetes mellitus patients without any treatment, type 2 diabetes mellitus patients with exposure to metformin only, type 2 diabetes mellitus patients taking oral hypoglycaemic agents along with metformin, type 2 diabetes mellitus patients taking only insulin, and type 2 diabetes mellitus patients taking insulin and oral hypoglycaemic agents. Fasting plasma glucose was determined using glucose oxidase-peroxidase method, glycated haemoglobin by high performance liquid chromatography, high-density lipoprotein and low-density lipoprotein by direct methods, cholesterol by cholesterol oxidase phenol 4-amino antipyrine peroxidase and triglycerides by glycerol phosphate oxidase-phenol 4-amino antipyrine peroxidase method. Serum levels of ferritin, insulin and hepcidin were evaluated using Enzyme-linked immunosorbent assay. Insulin resistance was assessed using homeostasis model assessment for insulin resistance. Data was analysed using SPSS 21. Of the 300 subjects, there were 50(16.66%) in each of the 6 groups. Overall, there were 144(48%) males and 155(51.66%) females. The mean age was significantly lower in the control group 34.72±7.87 compared to all the diabetic groups (p<0.05), and the same was the case with respect to all the parameters (p<0.05) except high-density lipoprotein (p>0.05). Besides, hepcidin level was significantly higher in the control group (p<0.05). Ferritin levels were significantly increased in newly-diagnosed T2DM subjects compared to the controls (p<0.05) while all other groups showed decreased ferritin levels (p<0.05). Hepcidin gave inverse correlation with glycated haemoglobin only in diabetics taking only metformin (r -0.27, p0.05). Anti-diabetes drugs not only addressed type 2 diabetes mellitus, but also reduced levels of ferritin and hepcidin that are found to play a role in diabetes development. |
36,800,554 | A National Physician Survey of Deintensifying Diabetes Medications for Older Adults With Type 2 Diabetes. | To determine physicians approach to deintensifying (reducingstopping) or switching hypoglycemia-causing medications for older adults with type 2 diabetes. In this national survey, U.S. physicians in general medicine, geriatrics, or endocrinology reported changes they would make to hypoglycemia-causing medications for older adults in three scenarios good health, HbA1c of 6.3% complex health, HbA1c of 7.3% and poor health, HbA1c of 7.7%. There were 445 eligible respondents (response rate 37.5%). In patient scenarios, 48%, 4%, and 20% of physicians deintensified hypoglycemia-causing medications for patients with good, complex, and poor health, respectively. Overall, 17% of physicians switched medications without significant differences by patient health. One-half of physicians selected HbA1c targets below guideline recommendations for older adults with complex or poor health. Most U.S. physicians would not deintensify or switch hypoglycemia-causing medications within guideline-recommended HbA1c targets. Physician preference for lower HbA1c targets than guidelines needs to be addressed to optimize deintensification decisions. |
36,800,530 | Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis A Mendelian Randomization Study. | We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs). Uncorrelated genetic variants associated with type 2 diabetes (n 231), fasting insulin (n 38), fasting glucose (n 71), and hemoglobin A1c (n 75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies and other large consortia. Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per 1-unit increase in the log-transformed odds ratio (OR) of type 2 diabetes, the OR was 1.06 (95% CI, 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI, 1.07-1.17) for gastric ulcer, 1.11 (95% CI, 1.03-1.20) for acute gastritis, 1.07 (95% CI, 1.01-1.13) for chronic gastritis, 1.08 (95% CI, 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI, 1.01-1.07) for diverticular disease, 1.08 (95% CI, 1.02-1.14) for acute pancreatitis, 1.09 (95% CI, 1.05-1.12) for cholelithiasis, 1.09 (95% CI, 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI, 1.17-1.43) for nonalcoholic fatty liver disease, 1.12 (95% CI, 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI, 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with six and one GDs, respectively. Associations were found between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in patients with type 2 diabetes. |
36,800,369 | An older diabetes-induced mice model for studying skin wound healing. | Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older Type 2 diabetes patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL6 mice were separated into groups fed a chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. We believe this unique old age phenotype contrasts with current mice models with induced diabetes. |
36,800,286 | GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes A Systematic Review and Meta-Analysis of Randomized Controlled Trials. | Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemichemorhhagic stroke and transient ischemic attacks (TIA) in type-2 diabetes mellitus (T2DM) remains undetermined. To pool effects of GLP-1RAs on adverse cerebrovascular outcomes and investigate impact of baseline variables on these effects. PubMed, EMbase, Web of Science, Cochrane Library, clinical trial registry websites were searched for randomized controlled trials(RCTs) for ≥24 weeks duration in adults with T2DM (PROSPERO CRD42022331547). Adjudicated cerebrovascular events in GLP-1RAs treatment versus control arms were pooled together to calculate risk ratio(RR) using fixed effects model. Subgroup analysis was performed based on individual drugs, treatment duration and baseline patient characteristics. Quality of evidence was assessed using GRADE framework. We identified 28 RCTs involving 74,148 patients (57% males median range, age 5852-67 years, BMI 3225.4-37.2kgm2, T2DM duration 93.5-15.4years, treatment duration 5224-259weeks). GLP-1 RAs use in T2DM was associated with significantly decreased risk of adverse cerebrovascular outcomes versus placeboactive comparator (RR,0.83 95%CI,0.76-0.91 I20%). Pooling data from cardiovascular outcome trials (n8), GLP-1RA treatment versus placebo was associated with reduced risk of nonfatal stroke(RR,0.85 95%CI, 0.76-0.94 I2 0%), but not fatal stroke (RR,0.80 95%CI,0.61-1.05 I2 0%). GLP-1RA use was associated with reduced risk of ischemic stroke (RCTs12 RR,0.73 95%CI,0.60-0.89 I20%), composite of ischemic strokeTIA (RCTs16 RR,0.76 95%CI,0.65-0.90 I20%), but not hemorrhagic stroke (RCTs3 RR,0.92 95%CI,0.51-1.64 I20%). Treatment benefits differed according to baseline eGFR and diabetes duration (p-interaction<0.1). Benefits were statistically significant for dulaglutide, subcutaneousoral semaglutide (p<0.05). Sensitivity analysis, excluding shorter-acting lixisenatide, eliminated the heterogeneity between individual GLP-1RA effects. GLP-1RAs, precisely longer acting formulations, reduced ischemic cerebrovascular events in T2DM. Observed benefits were significantly higher in patients with shorter T2DM duration and higher eGFR. |
36,800,181 | Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. | Hypertensive disorders in pregnancy (HDPs) are major causes of maternal and fetal morbidity and are observationally associated with future maternal risk of cardiovascular disease. However, observational results may be subject to residual confounding and bias. To investigate the association of HDPs with multiple cardiovascular diseases. A genome-wide genetic association study using mendelian randomization (MR) was performed from February 16 to March 4, 2022. Primary analysis was conducted using inverse-variance-weighted MR. Mediation analyses were performed using a multivariable MR framework. All studies included patients predominantly of European ancestry. Female-specific summary-level data from FinnGen (sixth release). Uncorrelated (r2<0.001) single-nucleotide variants (SNVs) were selected as instrumental variants from the FinnGen consortium summary statistics for exposures of any HDP, gestational hypertension, and preeclampsia or eclampsia. Genetic association estimates for outcomes were extracted from genome-wide association studies of 122 733 cases for coronary artery disease, 34 217 cases for ischemic stroke, 47 309 cases for heart failure, and 60 620 cases for atrial fibrillation. Genetically predicted HDPs were associated with a higher risk of coronary artery disease (odds ratio OR, 1.24 95% CI, 1.08-1.43 P .002) this association was evident for both gestational hypertension (OR, 1.08 95% CI, 1.00-1.17 P .04) and preeclampsiaeclampsia (OR, 1.06 95% CI, 1.01-1.12 P .03). Genetically predicted HDPs were also associated with a higher risk of ischemic stroke (OR, 1.27 95% CI, 1.12-1.44 P 2.87 × 10-4). Mediation analysis revealed a partial attenuation of the effect of HDPs on coronary artery disease after adjustment for systolic blood pressure (total effect OR, 1.24 direct effect OR, 1.10 95% CI, 1.02-1.08 P .02) and type 2 diabetes (total effect OR, 1.24 direct effect OR, 1.16 95% CI, 1.04-1.29 P .008). No associations were noted between genetically predicted HDPs and heart failure (OR, 0.97 95% CI, 0.76-1.23 P .79) or atrial fibrillation (OR, 1.11 95% CI, 0.65-1.88 P .71). The findings of this study provide genetic evidence supporting an association between HDPs and higher risk of coronary artery disease and stroke, which is only partially mediated by cardiometabolic factors. This supports classification of HDPs as risk factors for cardiovascular disease. |
36,799,940 | Human Epicardial Adipose Tissue Expresses Glucose-dependent Insulinotropic Polypeptide, Glucagon and Glucagon-Like Peptide 1 Receptors as Potential Targets of Pleiotropic Therapies. | Human Epicardial Adipose Tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular and immune cells. EAT is a white adipose tissue, albeit it also has brown-fat like or beige fat features. No muscle fascia divides EAT and myocardium this allows a direct interaction and cross talk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-Protein-Coupled Receptors, such as those for Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (GCG) and Glucagon-Like Peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell type localization specifically for GIPR and GCGR. EAT samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2±10.5 years mean ± SD). Microarray and immunohistochemistry analysis were performed. Microarray analysis showed that GIPR and GCGR messenger Ribonucleic Acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1(3776±1377 arbitrary unit (A.U.), 17.77±14.91 A.U., and 3.41±2.27 A.U., respectively). The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in Free Fatty Acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (p<0.01). EAT GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (p<0.01). Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.. Human Epicardial Adipose Tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular and immune cells. EAT is a white adipose tissue, albeit it also has brown-fat like or beige fat features. No muscle fascia divides EAT and myocardium this allows a direct interaction and cross talk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the Glucagon-Like Peptide 1 Receptor (GLP-1R) agonists. Human EAT is found to express the genes encoding the receptors of Glucose-dependent Insulinotropic Polypeptide (GIPR), Glucagon (GCGR) and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. EAT GIPR is inversely associated with genes involved in Free Fatty Acids (FFAs) oxidation and transport and with genes promoting FFAs biosynthesis and adipogenesis. EAT GCGR is correlated with genes promoting FFAs transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFAs biosynthesis and adipogenesis. As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPRGLP-1R agonists, and GLP-1RGIPRGCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ specific fat depots through G-Protein-Coupled Receptors may produce beneficial cardiovascular and metabolic effects. |
36,799,773 | Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder A Case Series Study. | Cocaine use remains a serious public health problem associated with a marked increase in overdose deaths in the past decade. No medications have yet been proven to be effective for the treatment of cocaine use disorder (CUD). Among the highly promising medications have been glucagon-like peptide 1 receptor agonists (GLP-1RA) that are currently used for the treatment of type 2 diabetes mellitus and weight management. Preclinically, GLP-1RAs have been shown to attenuate cocaine self-administration, however, this has not yet been demonstrated in a human laboratory study. The GLP-1RA extended-release exenatide is given as a once-weekly injection, which may be clinically advantageous for addressing medication nonadherence among individuals with CUD. Here, we assess feasibility and safety by reporting on 3 cases of patients with CUD who received 6 weeks of exenatide 2 mg subcutaneously once-weekly in an open-label fashion, along with standard individual drug counseling. We observed excellent attendance and compliance, along with positive end-of-study satisfaction ratings. The medication was well tolerated and without unexpected or severe adverse events. Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD should utilize a randomized controlled trial design and longer treatment duration. |
36,799,658 | Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma. | The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM. A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM. Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups. There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM. |
36,799,472 | The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes that reflect dietary intakes and fecal water content. | Obesity is a complex, multifactorial condition that is an important risk factor for noncommunicable diseases including cardiovascular disease and type 2 diabetes. While prevention and management require a healthy and energy balanced diet and adequate physical activity, the taxonomic composition and functional attributes of the colonic microbiota may have a supplementary role in the development of obesity. The taxonomic composition and metabolic capacity of the fecal microbiota of 286 women, resident in Auckland New Zealand, was determined by metagenomic analysis. Associations with BMI (obese, nonobese), body fat composition, and ethnicity (Pacific, n 125 NZ European women NZE, n 161) were assessed using regression analyses. The fecal microbiotas were characterized by the presence of three distinctive enterotypes, with enterotype 1 represented in both Pacific and NZE women (39 and 61%, respectively), enterotype 2 mainly in Pacific women (84 and 16%) and enterotype 3 mainly in NZE women (13 and 87%). Enterotype 1 was characterized mainly by the relative abundances of butyrate producing species, |
36,799,349 | A Cluster Randomized Controlled Trial Comparing Diabetes Prevention Program Interventions for OverweightObese Marshallese Adults. | This study compared the effectiveness of two Diabetes Prevention Program (DPP) interventions on weight loss among overweight and obese Marshallese adults. The study was a two-arm cluster randomized controlled trial conducted in 30 churches in Arkansas and Oklahoma. Marshallese adults with a body mass index ≥25 kgm |
36,799,324 | Dapagliflozin in DELIVER confirmation of the benefit with SGLT2 inhibitors in heart failure with preserved ejection fraction. | Gliflozins (sodium-glucose cotransporter type 2 inhibitors or SGLT2is) first demonstrated a reduction in hospitalisation for heart failure (hHF) in patients with type 2 diabetes (T2DM) at high cardiovascular risk. Then, a reduction in hHF (also combined with cardiovascular mortality) was reported in patients with heart failure, independently of the presence of T2DM. These placebo-controlled trials first concerned patients with heart failure and reduced left ventricular ejection fraction (LVEF) in DAPA-HF with dapagliflozin and EMPEROR-Reduced with empagliflozin. Afterwards, the benefit was observed in patients with preserved LVEF in EMPEROR-Preserved with empagliflozin, yet some doubt persisted in patients with LVEF > 60 %. The DELIVER study recently confirmed a significant reduction in the composite outcome hHF plus cardiovascular mortality (- 27 %) and in hHF (- 21 %) in patients (with or without T2DM) with heart failure and mildly reduced or preserved LVEF treated with dapagliflozin compared with placebo. The protection was noticed whatever the level of LVEF. These results reinforce the place of SGLT2is in international guidelines for the prevention or treatment of heart failure independently of the level of LVEF. SGLT2is represent the first pharmacological class that has proven its efficacy in patients with heart failure and preserved LVEF. Les gliflozines (inhibiteurs des cotransporteurs sodium-glucose de type 2 ou iSGLT2) ont d’abord montré une réduction des hospitalisations pour insuffisance cardiaque (hHF) chez des patients avec un diabète de type 2 (DT2) à haut risque cardiovasculaire. Ensuite, une réduction des hHF (également combinée à la mortalité cardiovasculaire) a été démontrée dans des études chez des patients avec insuffisance cardiaque, indépendamment de la présence d’un DT2. Ces essais contrôlés versus placebo ont d’abord concerné des patients avec insuffisance cardiaque à fraction d’éjection du ventricule gauche (FEVG) réduite (DAPA-HF avec la dapagliflozine, EMPEROR-Reduced avec l’empagliflozine). Ensuite, le bénéfice a été démontré chez des patients avec FEVG préservée dans EMPEROR-Preserved avec l’empagliflozine, mais avec un doute chez les patients avec FEVG > 60 %. L’étude DELIVER a récemment confirmé une réduction significative du critère combiné hHF plus mortalité cardiovasculaire (- 27 %) et des hHF (- 21 %) chez des patients (avec ou sans DT2) avec insuffisance cardiaque et FEVG modérément réduite ou préservée traités par la dapagliflozine par rapport à ceux sous placebo. La protection a été observée quelle que soit la valeur de la FEVG. Ces résultats confortent la place accordée dans les recommandations internationales aux iSGLT2 dans la prévention et le traitement de l’insuffisance cardiaque, que la FEVG soit réduite ou préservée. Les iSGLT2 représentent la première classe pharmacologique qui ait montré une efficacité chez les patients avec insuffisance cardiaque et FEVG préservée. |
36,799,298 | Large maternal waist circumference in relation to height is associated with high glucose concentrations in an early-pregnancy oral glucose tolerance test-A population-based study. | To explore the role of maternal anthropometric characteristics in early-pregnancy glycemia, we analyzed the associations and interactions of maternal early-pregnancy waist circumference (WC), height and pre-pregnancy body mass index (BMI) with plasma glucose concentrations in an oral glucose tolerance test (OGTT) at 12-16 weeks gestation. A population-based cohort of 1361 pregnant women was recruited in South Karelia, Finland, from March 2013 to December 2016. All participants had their WC, weight, height, HbA In the total cohort, 901 (66%) of women had an early-pregnancy WC ≥80 cm, which was associated with higher early-pregnancy HbA In our population-based cohort, early-pregnancy WHtR >0.5 was positively associated with both fasting and post-load glucose concentrations at 12-16 weeks gestation and performed better than BMI in the prediction of post-load glucose concentrations >90th percentile. Overall, our results underline the importance of evaluating maternal abdominal adiposity in gestational diabetes risk assessment. |
36,799,287 | The correlations between steady-state concentration, duration of action and molecular weight of GLP-1RAs and their efficacy and gastrointestinal side effects in patients with type 2 diabetes mellitus A systematic review and meta-analysis. | To assess the influence of steady-state concentration, duration of action and molecular weight of glucagon-like peptide-1 receptor (GLP-1RA) onefficacy and gastrointestinal side effects in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to April 2022. Randomized controlled trials (RCTs) comparing GLP-1RA versus non-GLP-1RA agents in patients with T2DM were included. Sensitivity analyses on steady-state concentration, duration of action and molecular weight of GLP-1RA were conducted. 113 RCTs were included. Greater HbA1c reduction between GLP-1RA users versus non-GLP-1RA users was observed in the high-steady-state-concentration stratum and long-acting stratum when compared with the low-steady-state-concentration stratum (P GLP-1RA with high steady-state concentration and long duration of action showed better hypoglycemic effect. GLP-1RA with high steady-state concentration, long duration of action and heavy molecular weight was associated with a lower risk of gastrointestinal adverse events. |
36,799,097 | Functional properties and in vitro starch digestibility of infrared treated (micronized) green banana flour. | The consumption of green banana flour (GBF) products has been linked with reduced glycemic index (GI) and low risk of type 2 diabetes and obesity. The purpose of this study was to investigate the effect of micronization (high-intensity infrared heating method) on the molecular, microstructure and in vitro starch digestibility of five GBF cultivars grown in South Africa. The GBF was micronized at three surface temperatures (90 °C, 120 °C, and 150 °C for 30 min) and the in vitro starch digestibility was determined with Megazyme kits. Micronization at the highest temperature (150 °C) increased the swelling power by 6.00% in all five GBF cultivars when compared to control (un-micronized GBF). Micronization slightly reduced the resistant starch (RS) of the GBF cultivars by up to 8.63%. The FHIA-01 cultivar showed the highest RS (86.50%), while Grande Naine-150 °C cultivar had the lowest RS (76.00%). Both micronized and control GBF exhibited similar XRD patterns with all cultivars and at all micronization temperatures. Similarly, the functional properties of the GBF were not altered by micronization when observed with FTIR. Scanning electron microscope showed changes in the surface morphology of starch granules after micronization and these were dependent on temperature. Overall, micronization at 120 °C showed the best improvement in functional properties of GBF and this makes it suitable for potential application for the manufacture of instant breakfast products, baked goods, and pasta. In addition, the micronized GBF cultivars retained high RS suggesting potential health benefits for people with diabetes and obesity. This article is protected by copyright. All rights reserved. |
36,799,018 | Trajectory of Glycated Hemoglobin Over Time Among Type 2 Diabetes Patients with Obesity on U-100 Basal-Bolus Insulin Regimen Using Real-World Data. | Obesity and complex insulin regimens add treatment challenges for T2DM patients on basal-bolus insulin treatment. A consequence of these challenges can be therapeutic inertia manifested in deteriorating or prolonged poor glycemic control. Identify patient clusters with poor glucose control among T2DM patients with obesity on basal-bolus insulin and recognize potential therapeutic inertia factors associated with poor control. HbA1c trajectories across a 3-year period were structured at 6-month intervals for a retrospective cohort of T2DM patients with obesity on basal-bolus insulin from the Veterans Health Administration (VHA) database. Based on each patients HbA1c longitudinal features, an unsupervised clustering procedure determined the numbers of clusters and associated trajectory patterns. A multinomial logistic regression was used to examine the association between HbA1c trajectory clusters and patient characteristicstreatment patterns. A total of 51,273 patients were included, of which 11.2% were in a subgroup with Persistent Missingness HbA1c. For those with sufficient HbA1c observations, cluster analysis indicated six distinct HbA1c trajectories Stable Low (35.8%), Stable High (20.8%), Descending Low (10.5%), Ascending Low (10.2%), Descending High (5.7%) and Ascending High (5.7%). Being black, not initiating non-insulin antihyperglycemic agents (SGLT2, GLP-1 or TZD) or concentrated insulin, low adherence (measured by proportion of days covered), and reduced insulin prescription refills are factors associated with poorer HbA1c clusters similar factors are associated with Persistent HbA1c Missingness. The present study found the potential for therapeutic inertia among a significant portion of T2DM patients with obesity on basal-bolus insulin. Segmenting T2DM patients based on HbA1c missingness and trajectories can inform disease management strategies. This article is protected by copyright. All rights reserved. |
36,798,918 | Association of Subclinical Hypothyroidism with Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus A Cross-Sectional Study. | Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are recognized as two common health problems. Metabolic diseases, such as dyslipidemia, obesity, and hypertension are known risk factors for NAFLD. In addition to these risk factors, other risk factors have been recently suggested, such as thyroid dysfunction. In this study, adult patients with T2DM were recruited. Various clinical and biochemical parameters including thyroid function tests, liver function tests, and liver sonography in all participants were assessed and compared between with and without NAFLD groups. Data from 926 diabetic patients were analyzed of which, 744 (80.3%) had fatty liver. The prevalence of subclinical hypothyroidism (SCH) in patients with NAFLD was 11.6% and in patients without NAFLD was 6.0% ( NAFLD is extremely common in patients with T2DM. The relationship between hypothyroidism and NAFLD is independent of other risk factors. |
36,798,908 | Correlation Between Mean Amplitude of Glycemic Excursion and Bone Turnover Markers in Patients with Type 2 Diabetes A Cross-Sectional Study. | The present study explores the relationship between glycemic excursion and bone turnover markers. A total of 250 patients with type 2 diabetes mellitus (T2DM) (142 female and 108 male patients) were enrolled in this study. All participants underwent 72 hours of continuous glycemic monitoring to evaluate the mean amplitude of glycemic excursions (MAGE) of each person. Bone turnover markers and other biochemical data were measured for each patient. Linear regression was performed to explore the relationship between bone turnover markers and glycemic excursion. A value of MAGE was negatively correlated to N-terminal propeptide of type 1 collagen (P1NP) female odds ratios (95% confidence interval) (OR (95% CI)), -2.516 (-5.389, 0.356) male -2.895, (-6.521, -0.731) and C-terminal telopeptide fragments of type-I collagen (β-CTX) female -0.025, (-0.036, 0.005) male -0.043, (-0.082, 0.003). MAGE was still negatively correlated with β-CTX female -0.036, (-0.198, -0.030) male -0.048, (-0.089, -0.007) after adjusting for clinical data and biochemical indices. An independent negative relationship between glycemic excursion and bone turnover markers in patients with T2DM was identified in this study. |
36,798,871 | Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes. | Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases. The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein-protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes. We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases. We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies. |
36,798,845 | Body composition of type 2 diabetes patients in Uganda A case-control study. | The prevalence of obesity among people diagnosed with Type 2 Diabetes Mellitus (T2DM) has been widely documented. However, the specific composition of this bodyweight remains largely unknown. The study aimed to understand the body composition of T2DM patients using the bioelectric impedance analysis technique, comparing findings to sex and agematched controls. A comparative case-control study was carried out among 139 known cases of Type 2 diabetes aged 18 to 78 years randomly sampled from the diabetic clinic of Mbarara Regional Referral Hospital. We matched them to 139 hospital controls who were healthy non-diabetic attendants. Body composition parameters were computed and summarized as medians and interquartile ranges. Differences in the medians of body composition parameters were further assessed using the Mann- Whitney U test. Fat-free and fat mass indices were derived to offer a precise estimation of body composition parameters adjusted for height differences among study participants. Cases had significantly higher median systolic blood pressure, pulse rate, weight, Body Mass Index (BMI), Waist-Hip Ratio (WHR), total fat percentage, fat mass amount, Fat Mass Index, visceral fat, and metabolic age than their counterparts, whereas controls had significantly higher median total body water percentage versus cases. The highest significant differences occurred in fat percentage composition (Cases β 6.9 (95% C.I 4.4, 9.4) Controls Ref) followed by visceral fat (Cases β 3.5 (95% C.I 2.5, 4.4) controls Ref) and Fat Mass Index (Cases 95% C.I 2.6 (95% C.I 1.6, 3.7). Cases had significantly higher Fat Mass Index, visceral fat and fat percentage (all p<0.05) than controls. Routine assessment of body composition of T2DM patients needs to be done to assess the amount, type and pattern of weight gain to prevent increases in adiposity. |
36,798,477 | Protective Effects of Rifampicin and Its Analog Rifampicin Quinone in a Mouse Model of Obesity-Induced Type 2 Diabetes. | Advanced glycation end-products (AGEs) form when glucose reacts non-enzymatically with proteins, leading to abnormal protein function, oxidative stress, and inflammation. AGEs are associated with aging and age-related diseases their formation is aggravated during diabetes. Therefore, drugs preventing AGE formation can potentially treat diabetic complications, positively affecting health. Earlier, we demonstrated that rifampicin and its analogs have potent anti-glycating activities and increase the life span of |
36,798,008 | Assessment of prediabetes knowledge among adults in Al-Madinah, Saudi Arabia. | null |
36,797,835 | COVID-19 and diabetes mellitus a review of the incidence, pathophysiology and management of diabetes during the pandemic. | The COVID-19 pandemic has changed the landscape of modern medicine on a global scale. An emerging concern is the recognition of a bidirectional relationship between COVID-19 and diabetes. Diabetes is a risk factor for severe COVID-19 illness. Intriguingly, recent epidemiological and This review provides an overview of our current understanding of the incidence and prevalence of diabetes in relation to the COVID-19 pandemic, highlights studies evaluating SARS-CoV-2s beta cell tropism and its effects on insulin secretion and sensitivity and evaluates the impact of the pandemic on diabetes management and metabolic control. Epidemiological studies have noted an increase in the incidence of new-onset diabetes associated with COVID-19 in patients with phenotypes of type 1 diabetes, type 2 diabetes and Ketosis-Prone Diabetes. Prospective studies are needed to fully elucidate the association between COVID-19 and diabetes and to characterize persons at risk of developing diabetes after SARS-CoV-2 infection, identify those who should be screened for diabetes, and determine the natural histories of different forms of diabetes associated with COVID-19. The COVID-19 pandemic has affected medical care worldwide. Healthcare systems have been overwhelmed during ‘surges’ of COVID-19 illness, and access to care has been affected during prolonged lockdowns. COVID-19 is caused by the SARS-CoV-2 virus, which is highly contagious. Infection with SARS-CoV-2 can lead to serious illness, primarily in the lungs, but it often affects many other organ systems, leading to disability and death. Recent studies show that persons with diabetes can have a more severe course of illness if infected with SARS-CoV-2. There is also growing evidence that COVID-19 may cause diabetes or worsen preexisting diabetes. In this review, we discuss the findings of studies that show an increase in the frequency of diabetes diagnosed worldwide during the COVID-19 pandemic. We also examine recent data that suggest SARS-CoV-2 can infect and damage the insulin-producing cells in the pancreas. Finally, we provide an overview of the impact of COVID-19 on the management of patients with diabetes, and the emerging use of telemedicine in diabetes care. |
36,797,785 | Maternal hypertensive disorders during pregnancy and the risk of offspring diabetes mellitus in childhood, adolescence, and early adulthood a nationwide population-based cohort study. | Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood. Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offsprings age as the time scale. During a follow-up of up to 41 (median 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR1.27, 95% CI1.20-1.34), as well as for type 2 diabetes (HR1.57, 95% CI1.38-1.78) and gestational diabetes (HR1.37, 95% CI1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR1.08, 95% CI0.98-1.18). Offspring of mothers with gestational hypertension (HR1.37, 95% CI1.00-1.88) or preeclampsia (HR1.62, 95% CI1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR2.00, 95% CI1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR1.41, 95%CI1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR4.64, 95%CI3.85-5.60) than offspring of mothers with HDP or diabetes alone. Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations. |
36,797,773 | Curalin Supplement for Patients with Type 2 Diabetes Mellitus. | To examine the efficacy and safety of Curalin supplement in patients with type 2 diabetes. Adult patients with type 2 diabetes were randomized 11 to receive Curalin supplement or placebo. The primary endpoint was HbA1c decrease at 1-month. The secondary endpoint was decrease in HbA1c by more than 0.5% and 1%, and change in 7 daily blood glucose measurements. Satisfaction questionnaire was used as an exploratory endpoint. Safety variables and adverse events were assessed. After 1 month of intervention, HbA1c was reduced by 0.94% in the Curalin arm vs. 0.4% in the placebo arm (P0.008). 72% of Curalin patients had decreased HbA1c levels >0.5% vs. 35% in the placebo arm (P<0.05). Treatment Satisfaction Questionnaire indicated that Curalin arm patients reported higher overall satisfaction. Curalin treatment significantly reduced HbA1c over a 1-month period and was well-tolerated. This article is protected by copyright. All rights reserved. |
36,797,706 | Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio as potential cardiovascular disease risk factors an analysis of UK biobank data. | The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TGHDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations. A total of 403,335 participants from the UK Biobank with data for TyG index and TGHDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TGHDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations. During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TGHDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TGHDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG indexs association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TGHDL-C ratios association with CVD, respectively. Elevated baseline TyG index and TGHDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension. |
36,797,624 | Effect of Biopsychosocial Factors on Glycemic Control in Type 2 Diabetes Mellitus. | To investigate the effect of diabetic patients biopsychosocial factors on type 2 diabetes mellitus (T2DM) outcomes to contribute to diabetes mellitus management. Cross-sectional descriptive study. Place and Duration of the Study Department of Family Medicine, School of Medicine, Firat University, Turkey, from October 2021 to March 2022. A total of 210 type 2 diabetic patients were included. The sociodemographic form, Beck depression inventory (BDI), multidimensional perceived social support scale (MSPSS), general self-efficacy scale (GES), and Diabetes self-care activities scale (DSCA) were used to assess the biopsychosocial factors. Controlled diabetes and uncontrolled diabetes classification was made according to HbA1c level (HbA1c cut-off value ≤7%). The median duration of T2DM (p0.001), total cholesterol level (p0.004) and fasting plasma glucose (p<0.001) were found to be higher in the uncontrolled diabetes group than in the controlled diabetes group. Spearman correlation test results showed a significant negative relationship between the scores of Beck depression and total cholesterol (r -0.157, p 0.023). There is a significant positive correlation between social support and total cholesterol (r0.343, p<0.001), LDL (r0.149, p 0.031), triglyceride (r0.165, p 0.017), DSCA general diet score (r0.367, p<0.001), DSCA physical activities (r0.221, p 0.001), DSCA glucose monitoring (r0.302, p<0.001), DSCA foot care (r0.311, p<0.001), and DSCA total scores (r0.401, p<0.001). The present study showed that high BDI score was associated with low diabetes self-care score and presence of complications. Individuals self-efficacy and high perception of social support were associated with increased diabetic self-care scores. Social support, Perception, Self care, Diabetes mellitus type 2, Diabetes complications, Depression. |
36,797,616 | Common pathogenetic pathways of Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. | Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are two cardinal manifestations of the metabolic syndrome, which is becoming a growing global pandemic and a health care burden. They constitute a pathogenetic duo, with complex interplay through interrelated, but still partly understood, pathophysiological pathways, which mainly involve lipid toxicity (expressed through increased hepatic de novo lipogenesis, hepatic and peripheral insulin resistance, upregulated lipolysis, lipoprotein abnormalities, hyperinsulinemia), impaired autophagy, mitochondrial dysfunction, endoplasmic reticulum stress, adipose tissue dysfunction with a consequent latent inflammatory state, inflammasome activation, genetic and epigenetic factors, altered gut microbiota and finally dietary factors. In this review, based on data from recent studies and focusing mainly on common molecular mechanisms, we will highlight the common pathophysiological grounds and the interplay between NAFLD and T2DM. |
36,797,025 | Couple-based lifestyle intervention to prevent type 2 diabetes protocol for a randomised pilot trial. | Type 2 diabetes is prevalent among US adults. Lifestyle interventions that modify health behaviours prevent or delay progression to diabetes among individuals at high risk. Despite the well-documented influence of individuals social context on their health, evidence-based type 2 diabetes prevention interventions do not systematically incorporate participants romantic partners. Involving partners of individuals at high risk for type 2 diabetes in primary prevention may improve engagement and outcomes of programmes. The randomised pilot trial protocol described in this manuscript will evaluate a couple-based lifestyle intervention to prevent type 2 diabetes. The objective of the trial is to describe the feasibility of the couple-based intervention and the study protocol to guide planning of a definitive randomised clinical trial (RCT). We used community-based participatory research principles to adapt an individual diabetes prevention curriculum for delivery to couples. This parallel two-arm pilot study will include 12 romantic couples in which at least one partner (ie, target individual) is at risk for type 2 diabetes. Couples will be randomised to either the 2021 version of the CDCs PreventT2 curriculum designed for delivery to individuals (six couples), or PreventT2 Together, the adapted couple-based curriculum (six couples). Participants and interventionists will be unblinded, but research nurses collecting data will be blinded to treatment allocation. Feasibility of the couple-based intervention and the study protocol will be assessed using both quantitative and qualitative measures. This study has been approved by the University of Utah IRB (143079). Findings will be shared with researchers through publications and presentations. We will collaborate with community partners to determine the optimal strategy for communicating findings to community members. Results will inform a subsequent definitive RCT. NCT05695170. |
36,796,776 | Type 2 diabetes remission in Australian primary care Protocol for an implementation study of the DiRECT-Aus trial. | Type 2 diabetes is one of the most common chronic conditions managed in Australian general practice. DiRECT-Aus is replicating the UK Diabetes Remission Clinical Trial (DiRECT) in general practices across NSW. The aim of the study will be to explore the implementation of DiRECT-Aus to inform future scale-up and sustainability. This is a cross-sectional qualitative study using semi-structured interviews to explore the experiences of patients, clinicians and stakeholders in the DiRECT-Aus trial. The Consolidated Framework for Implementation Research (CFIR) will be used to guide the exploration of the implementation factors, and the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to report on implementation outcomes. Interviews will be conducted with patients and key stakeholders. Initial coding will be based on the CFIR, with inductive coding used to develop the themes. This implementation study will identify factors to be considered and addressed so that future scale-up and national delivery will be equitable and sustainable. |
36,796,719 | Treatment with semaglutide, a GLP-1 receptor agonist, improves extracellular matrix remodeling in the pancreatic islet of diet-induced obese mice. | The extracellular matrix (ECM) is fundamental for the normal endocrine functions of pancreatic islet cells and plays key roles in the pathophysiology of type 2 diabetes. Here we investigated the turnover of islet ECM components, including islet amyloid polypeptide (IAPP), in an obese mouse model treated with semaglutide, a glucagon-like peptide type 1 receptor agonist. Male one-month-old C57BL6 mice were fed a control diet (C) or a high-fat diet (HF) for 16 weeks, then treated with semaglutide (subcutaneous 40 μgkg every three days) for an additional four weeks (HFS). The islets were immunostained and gene expressions were assessed. Comparisons refer to HFS vs HF. Thus, IAPP immunolabeling and beta-cell-enriched beta-amyloid precursor protein cleaving enzyme (Bace2, -40 %) and heparanase immunolabeling and gene (Hpse, -40 %) were mitigated by semaglutide. In contrast, perlecan (Hspg2, 900 %) and vascular endothelial growth factor A (Vegfa, 420 %) were enhanced by semaglutide. Also, semaglutide lessened syndecan 4 (Sdc4, -65 %) and hyaluronan synthases (Has1, -45 % Has2, -65 %) as well as chondroitin sulfate immunolabeling, and collagen type 1 (Col1a1, -60 %) and type 6 (Col6a3, -15 %), lysyl oxidase (Lox, -30 %) and metalloproteinases (Mmp2, -45 % Mmp9, -60 %). Semaglutide improved the turnover of islet heparan sulfate proteoglycans, hyaluronan, chondroitin sulfate proteoglycans, and collagens in the islet ECM. Such changes should contribute to restoring a healthy islet functional milieu and should reduce the formation of cell-damaging amyloid deposits. Our findings also provide additional evidence for the involvement of islet proteoglycans in the pathophysiology of type 2 diabetes. |
36,796,575 | Elevated remnant cholesterol increase 6-year T2DM onset risk. | To investigate the association of remnant cholesterol (RC) with future type 2 diabetes mellites (T2DM) risk, and to assess the underlying impact of some recognized risk factors on it. A total of 11,468 nondiabetic adults in rural China were recruited in 2007-2008 and followed up in 2013-2014. Logistic regression was used to assess the risk of incident T2DM by quartiles of baseline RC, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Association of the combinations of RC and low-density lipoprotein cholesterol (LDL-C) with T2DM risk were further evaluated. Multivariable adjusted OR (95% CI) for incident T2DM associated with quartile 4 versus quartile 1 of RC was 2.72 (2.05-3.62). Per 1-standard deviation (SD) increases in RC levels was associated with a 34% higher T2DM risk. However, gender modified the specific association (P Elevated RC levels increase T2DM risk in rural Chinese populations. In those who cannot control their risk by lowering LDL-C levels, the goal of lipid-lowering therapy can be shifted to RC. |
36,796,421 | Post-Load Insulin Secretion Patterns are Associated with Glycemic Status and Diabetic Complications in Patients with Type 2 Diabetes Mellitus. | To examine whether the different patterns of post-load insulin secretion can identify the heterogeneity of type 2 diabetes mellitus (T2DM). Six hundred twenty-five inpatients with T2DM at Jining No. 1 Peoples Hospital were recruited from January 2019 to October 2021. The 140 g steamed bread meal test (SBMT) was conducted on patients with T2DM, and glucose, insulin, and C-peptide levels were recorded at 0, 60, 120, and 180 min. To avoid the effect of exogenous insulin, patients were categorized into three different classes by latent class trajectory analysis based on the post-load secretion patterns of C-peptide. The difference in short- and long-term glycemic status and prevalence of complications distributed among the three classes were compared by multiple linear regression and multiple logistic regression, respectively. There were significant differences in long-term glycemic status (e. g., HbA1c) and short-term glycemic status (e. g., mean blood glucose, time in range) among the three classes. The difference in short-term glycemic status was similar in terms of the whole day, daytime, and nighttime. The prevalence of severe diabetic retinopathy and atherosclerosis showed a decreasing trend among the three classes. The post-load insulin secretion patterns could well identify the heterogeneity of patients with T2DM in short- and long-term glycemic status and prevalence of complications, providing recommendations for the timely adjustment in treatment regimes of patients with T2DM and promotion of personalized treatment. |
36,796,312 | Patterns of new glucagon-like peptide-1 receptor agonist use in patients with type 2 diabetes during 2014-2019 from a US database prescriber and patient characteristics. | null |
36,796,293 | The nature of the binding between insulin receptor and serotonin transporter in placenta (review). | The interplay between the insulin receptor (IR) and serotonin transporter (SERT) allows reciprocal regulation of each others physiological roles to ensure appropriate responses to specific environmental and developmental signals. The studies reported herein provided substantial evidence of how insulin signaling influences the modification and trafficking of SERT to the plasma membrane via enabling its association with specific endoplasmic reticulum (ER) proteins. While insulin signaling is important for the modifications of SERT proteins, the fact that phosphorylation of IR was significantly down-regulated in the placenta of SERT knock out (KO) mice suggests that SERT also regulates IR. Further suggestive of SERT functional regulation of IR, SERT-KO mice developed obesity and glucose intolerance with symptoms similar to those of type 2 diabetes. The picture emerging from those studies proposes that the interplay between IR and SERT maintains conditions supportive of IR phosphorylation and regulates insulin signaling in placenta which ultimately enables the trafficking of SERT to the plasma membrane. IR-SERT association thus appears to play a protective metabolic role in placenta and is impaired under diabetic conditions. This review focuses on recent findings describing the functional and physical associations between IR and SERT in placental cells, and the dysregulation of this process in diabetes. |
36,796,216 | Combined systematic pharmacology and urine metabonomics to study the therapeutic mechanism of type 2 diabetic treated with the herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa Pradeep. | The herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa Pradeep (DG) is commonly used in the treatment of type 2 diabetes (T2DM) in traditional Chinese medicine (TCM). The drug pair DG was designed by Dr. Zhu chenyu to improve the treatment of T2DM. This study combined with systematic pharmacology and urine metabonomics to explore the mechanism of DG in the treatment of T2DM. The therapeutic effect of DG on T2DM was evaluated by fasting blood glucose (FBG) and biochemical indexes. Systematic pharmacology was used to screen the active components and targets that may be related to DG. Metabonomics was established to find urinary metabolites and pathways that may be induced by DG. Finally, integrate the results of these two parts for mutual verification. FBG and biochemical indexes showed that DG could reduce FBG and adjust the related biochemical indexes. Metabolomics analysis indicated that 39 metabolites were related to DG for T2DM treatment. In addition, systematic pharmacology showed compounds and potential targets which were associated with DG. Finally, 12 promising targets were selected as targets for T2DM therapy by integrating the results. The combination of metabonomics and systematic pharmacology based on LC-MS is feasible and effective, which provides strong support for exploring the effective components and pharmacological mechanism of TCM. |
36,796,135 | Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle. | Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (dbdb) mice but not in obese obob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from dbdb mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in dbdb mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes. |
36,796,023 | Comprehensive care in type 2 diabetes from DiabeIMSS to CADIMSS. | In diabetes, obtaining optimal control is key to reducing chronic complications. Unfortunately, not all patients achieve the recommended goals. Therefore, the challenges to develop and evaluate comprehensive care models are enormous. In October 2008, the Diabetic Patient Care Program (DiabetIMSS) was designed and implemented in family medicine. Its principal component is the multidisciplinary team (doctor, nurse, psychologist, dietitian, dentist, and social worker) that offers coordinated health care monthly medical consultation and individual, family and group education on self-care and prevention of complications for 12 months. Due to the COVID-19 pandemic, the percentage of attendance at the DiabetIMSS modules decreased significantly. This is how the Medical Director considered it necessary to strengthen them, and the Diabetes Care Centers (CADIMSS) arose. In addition to providing medical care with a comprehensive and multidisciplinary approach, the CADIMSS encourages the co-responsibility of the patient and his family. It consists of monthly medical consultation and nursing staff provides monthly educational sessions for 6 months. Pending tasks remain and there are still areas of opportunity to modernize and reorganize services that contribute to improving the health of the population with diabetes. En un paciente con diabetes, la obtención de un control óptimo es clave para reducir las complicaciones crónicas. Desafortunadamente, no todos los pacientes logran las metas recomendadas. Por ello, son substanciales los desafíos para desarrollar y evaluar modelos de atención integral. En octubre del 2008, se diseñó e implementó el Programa de Atención al Paciente Diabético (DiabetIMSS) en medicina familiar. Su componente básico es el equipo multidisciplinario (médico, enfermera, psicólogo, dietista, dentista y trabajador social) que ofrece asistencia sanitaria coordinada, consulta médica mensual y educación individual, familiar y grupal sobre autocuidado y prevención de complicaciones durante 12 meses. Debido a la pandemia de COVID-19, el porcentaje de asistencia a los módulos DiabetIMSS disminuyó importantemente. Es así como la Dirección de Prestaciones Médicas consideró necesario su fortalecimiento, por lo que surgen los Centros de Atención a la Diabetes (CADIMSS). Además de proporcionar atención médico-asistencial con enfoque integral y multidisciplinario, en los CADIMSS se fomenta la corresponsabilidad del paciente y su familia, y se otorga consulta médica mensual y sesiones educativas a cargo de personal de enfermería durante 6 meses. Sin embargo, siguen tareas pendientes, y aún hay áreas de oportunidad para modernizar y reorganizar los servicios que contribuyan a mejorar la salud de la población con diabetes. |
36,795,707 | Protocol Implementation and evaluation of an adolescent-mediated intervention to improve glycemic control and diabetes self-management among Samoan adults. | Diagnoses of Type 2 Diabetes in the United States have more than doubled in the last two decades. One minority group at disproportionate risk are Pacific Islanders who face numerous barriers to prevention and self-care. To address the need for prevention and treatment in this group, and building on the family-centered culture, we will pilot test an adolescent-mediated intervention designed to improve the glycemic control and self-care practices of a paired adult family member with diagnosed diabetes. We will conduct a randomized controlled trial in American Samoa among n 160 dyads (adolescent without diabetes, adult with diabetes). Adolescents will receive either a six-month diabetes intervention or a leadership and life skills-focused control curriculum. Aside from research assessments we will have no contact with the adults in the dyad who will proceed with their usual care. To test our hypothesis that adolescents will be effective conduits of diabetes knowledge and will support their paired adult in the adoption of self-care strategies, our primary efficacy outcomes will be adult glycemic control and cardiovascular risk factors (BMI, blood pressure, waist circumference). Secondarily, since we believe exposure to the intervention may encourage positive behavior change in the adolescent themselves, we will measure the same outcomes in adolescents. Outcomes will be measured at baseline, after active intervention (six months post-randomization) and at 12-months post-randomization to examine maintenance effects. To determine potential for sustainability and scale up, we will examine intervention acceptability, feasibility, fidelity, reach, and cost. This study will explore Samoan adolescents ability to act as agents of familial health behavior change. Intervention success would produce a scalable program with potential for replication in other family-centered ethnic minority groups across the US who are the ideal beneficiaries of innovations to reduce chronic disease risk and eliminate health disparities. |
36,795,328 | Association Between Diabetes Severity and Risks of COVID-19 Infection and Outcomes. | Little is known about whether diabetes increases the risk of COVID-19 infection and whether measures of diabetes severity are related to COVID-19 outcomes. Investigate diabetes severity measures as potential risk factors for COVID-19 infection and COVID-19 outcomes. In integrated healthcare systems in Colorado, Oregon, and Washington, we identified a cohort of adults on February 29, 2020 (n 1,086,918) and conducted follow-up through February 28, 2021. Electronic health data and death certificates were used to identify markers of diabetes severity, covariates, and outcomes. Outcomes were COVID-19 infection (positive nucleic acid antigen test, COVID-19 hospitalization, or COVID-19 death) and severe COVID-19 (invasive mechanical ventilation or COVID-19 death). Individuals with diabetes (n 142,340) and categories of diabetes severity measures were compared with a referent group with no diabetes (n 944,578), adjusting for demographic variables, neighborhood deprivation index, body mass index, and comorbidities. Of 30,935 patients with COVID-19 infection, 996 met the criteria for severe COVID-19. Type 1 (odds ratio OR 1.41, 95% CI 1.27-1.57) and type 2 diabetes (OR 1.27, 95% CI 1.23-1.31) were associated with increased risk of COVID-19 infection. Insulin treatment was associated with greater COVID-19 infection risk (OR 1.43, 95% CI 1.34-1.52) than treatment with non-insulin drugs (OR 1.26, 95% 1.20-1.33) or no treatment (OR 1.24 1.18-1.29). The relationship between glycemic control and COVID-19 infection risk was dose-dependent from an OR of 1.21 (95% CI 1.15-1.26) for hemoglobin A1c (HbA1c) < 7% to an OR of 1.62 (95% CI 1.51-1.75) for HbA1c ≥ 9%. Risk factors for severe COVID-19 were type 1 diabetes (OR 2.87 95% CI 1.99-4.15), type 2 diabetes (OR 1.80 95% CI 1.55-2.09), insulin treatment (OR 2.65 95% CI 2.13-3.28), and HbA1c ≥ 9% (OR 2.61 95% CI 1.94-3.52). Diabetes and greater diabetes severity were associated with increased risks of COVID-19 infection and worse COVID-19 outcomes. |
36,795,181 | Exercise-induced microbial changes in preventing type 2 diabetes. | The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut microbiota. Here we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and diabetes. We found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students cohort. We additionally showed that those microbial changes correlated more with handgrip strength, a simple but valuable biomarker suggestive of the diabetes states, than maximum oxygen intake, one of the key surrogates for endurance training. Moreover, the causal relationships among exercise, risks for diabetes, and gut microbiota were explored based on mediation analysis. We propose that the protective roles of exercise against type 2 diabetes are mediated, at least partly, by the gut microbiota. |
36,794,003 | High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients. | Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of |
36,793,876 | Development process of a clinical guideline to manage type 2 diabetes in adults by Ayurvedic practitioners. | Type 2 diabetes mellitus (T2DM), a common chronic health condition, has major health and socioeconomic consequences. In the Indian subcontinent, it is a health condition for which individuals commonly consult Ayurvedic (traditional medical system) practitioners and use their medicines. However, to date, a good quality T2DM clinical guideline for Ayurvedic practitioners, grounded on the best available scientific evidence, is not available. Therefore, the study aimed to systematically develop a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. The development work was guided by the UKs National Institute for Health and Care Excellence (NICE) manual for developing guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. First, a comprehensive systematic review was conducted which evaluated Ayurvedic medicines effectiveness and safety in managing T2DM. In addition, the GRADE approach was used for assessing the certainty of the findings. Next, using the GRADE approach, the Evidence-to-Decision framework was developed, and we focused on glycemic control and adverse events. Subsequently, based on the Evidence-to-Decision framework, a Guideline Development Group of 17 international members made recommendations on Ayurvedic medicines effectiveness and safety in T2DM. These recommendations formed the basis of the clinical guideline, and additional generic content and recommendations were adapted from the T2DM Clinical Knowledge Summaries of the Clarity Informatics (UK). The feedback given by the Guideline Development Group on the draft version was used to amend and finalize the clinical guideline. A clinical guideline for managing T2DM in adults by Ayurvedic practitioners was developed, which focuses on how practitioners can provide appropriate care, education, and support for people with T2DM (and their carers and family). The clinical guideline provides information on T2DM, such as its definition, risk factors, prevalence, prognosis, and complications how it should be diagnosed and managed through lifestyle changes like diet and physical activity and Ayurvedic medicines how the acute and chronic complications of T2DM should be detected and managed (including referral to specialists) and advice on topics like driving, work, and fasting including during religioussocio-cultural festivals. We systematically developed a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. |
36,793,785 | Studies on alpha-synuclein and islet amyloid polypeptide interaction. | null |
36,793,541 | Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus. | To quantitatively evaluate the iron deposition and volume changes in deep gray nuclei according to threshold-method of quantitative susceptibility mapping (QSM) acquired by strategically acquired gradient echo (STAGE) sequence, and to analyze the correlation between the magnetic susceptibility values (MSV) and cognitive scores in type 2 diabetes mellitus (T2DM) patients. Twenty-nine patients with T2DM and 24 healthy controls (HC) matched by age and gender were recruited in this prospective study. QSM images were used to evaluate whole-structural volumes (V Compared with HC group, the MSV In T2DM patients, excessive and heterogeneous iron deposition as well as volume loss occurs in deep gray nuclei. The MSV in high iron regions can better evaluate the distribution of iron, which is related to the decline of cognitive function. |
36,793,528 | Angina Bullosa Hemorrhagica. | Angina bullosa hemorrhagica (ABH) is an underrecognized, benign condition of the oral mucosa. A 26-year-old female patient with type 2 diabetes mellitus presented with sudden-onset painless blood blisters on her soft palate. ABH was clinically diagnosed based on the clinical presentation and spontaneously resolved. Some medical conditions, including diabetes mellitus, hypertension, and inhaled steroids, can be a risk factor of ABH. Clinicians should be aware of ABH and consider the possibility of an associated underlying condition. |
36,793,475 | Triglyceride-glucose index for the detection of subclinical heart failure with preserved ejection fraction in patients with type 2 diabetes. | The triglyceride-glucose (TyG) index has been identified as a reliable and simple surrogate of insulin resistance. In this study, we sought to determine the association between TyG index and cardiac function among asymptomatic individuals with type 2 diabetes (T2DM) without history of any cardiovascular disease. The cross-sectional study enrolled 180 T2DM patients without cardiac symptoms. Heart failure with preserved ejection fraction (HFpEF) was defined as Heart Failure Association (HFA)-PEFF score ≥ 5 points. A total of 38 (21.1%) diabetic patients were identified with HFpEF. Compared with the low-TyG group (TyG index <9.47), patients in high-TyG group (TyG index ≥9.47) showed increased risk of metabolic syndrome and diastolic dysfunction ( The TyG index showed a positive correlation with the risk of subclinical HFpEF in patients with T2DM, providing a new marker to predict and treat HFpEF in diabetes. |
36,793,285 | Clinical effectiveness of second-line antihyperglycemic drugs on major adverse cardiovascular events An emulation of a target trial. | The cardiovascular benefits of multiple antihyperglycemic drugs as add-on therapies to metformin in the real-practice are unclear. This study aimed to directly compare major adverse cardiovascular events (CVE) associated with these multiple drugs. An emulation of a target trial was conducted using a retrospective-cohort data of type 2 diabetes mellitus (T2DM) prescribed with second-line drugs on top of metformin, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinediones (TZD) and sulfonylureas (SUs). We applied inverse probability weighting and regression adjustment using intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. Average treatment effects (ATE) were estimated using SUs as the reference. Among 25,498 patients with T2DM, 17,586 (69.0%), 3,261 (12.8%), 4,399 (17.3%), and 252 (1.0%) received SUs, TZD, DPP4i, and SGLT2i. Median follow-up time was 3.56 (1.36-7.00) years. CVE was identified in 963 patients. The ITT and modified ITT approaches showed similar results the ATE (i.e., the difference of CVE risks) for SGLT2i, TZD, and DPP4i compared to SUs were -0.020(-0.040, -0.0002), -0.010(-0.017, -0.003), and -0.004(-0.010, 0.002), respectively, indicating 2% and 1% significant absolute risk reduction in CVE in SGLT2i and TZD compared to SUs. These corresponding effects were also significant in the PPA with ATEs of -0.045(-0.060, -0.031), -0.015(-0.026, -0.004), and -0.012(-0.020, -0.004). In addition, SGLT2i had 3.3% significant absolute risk reduction in CVE relative to DPP4i. Our study demonstrated benefits of SGLT2i and TZD in reducing CVE in T2DM patients compared to SUs when added to metformin. |
36,793,278 | Factors associated with gastrointestinal side effects after liraglutide treatment for type 2 diabetes. | To identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM). T2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values. A total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p <0.05). In the final regression model, AGI use (adjusted OR4.01, 95%CI 1.90-8.45, p<0.001), gastrointestinal diseases (adjusted OR3.29, 95%CI 1.51-7.18, p0.003), TSH (adjusted OR1.79, 95%CI 1.28-2.50, p0.001) and male sex (adjusted OR0.19, 95%CI 0.10-0.37, p<0.001) were independently associated with GSEA. Furthermore, ROC curve analysis confirmed that TSH values of 1.33 and 2.30 in females and males, respectively, were useful thresholds for predicting GSEA. This study suggests that the combination of AGI, concomitant gastrointestinal diseases, female sex and higher TSH levels are independent risk factors of GSEA of liraglutide treatment in patients with T2DM. Further research is warranted to elucidate these interactions. |
36,793,276 | Evolution of sodium-glucose co-transporter 2 inhibitors from a glucose-lowering drug to a pivotal therapeutic agent for cardio-renal-metabolic syndrome. | Cardio-renal-metabolic (CRM) syndrome, which involves type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and heart failure (HF), is a serious healthcare issue globally, with high morbidity and mortality. The disorders that comprise CRM syndrome are independent can mutually affect and accelerate the exacerbation of each other, thereby substantially increasing the risk of mortality and impairing quality of life. To manage CRM syndrome by preventing vicious interactions among individual disorders, a holistic treatment approach that can simultaneously address multiple disorders underpinning CRM syndrome is of great importance. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) lower blood glucose levels by inhibiting glucose reabsorption in the renal proximal tubule and were first indicated for the treatment of T2DM. Several cardiovascular outcome trials have demonstrated that SGLT2i not only lower blood glucose but also reduce the risk of hospitalization for HF and worsening renal function in patients with T2DM. Results have also suggested that the observed cardiorenal benefits of SGLT2i may be independent of their blood glucose-lowering effects. Several randomized controlled trials subsequently assessed the efficacy and safety of SGLT2i in patients without T2DM, and revealed considerable benefits of SGLT2i treatment against HF and CKD, regardless of the presence of T2DM. Thus, SGLT2i have become an essential therapeutic option to prevent the onset, slow the progression, and improve the prognosis of CRM syndrome. This review assesses the evolution of SGLT2i from a glucose-lowering drug to a therapeutic agent for CRM syndrome by evaluating epoch-making clinical studies, including randomized control trials and real-world studies. |
36,793,123 | Maturity-onset diabetes of the young secondary to HNF1B variants (HNF1B-MODY) a series of 10 patients from a single diabetes center. | Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant condition and represents 1-5% of all cases of diabetes mellitus. MODY is often misdiagnosed as type 1 or type 2 diabetes. The rare subtype 5 (HNF1B-MODY) is due to hepatocyte nuclear factor 1β (HNF1B) molecular alteration and is remarkable for its multisystemic phenotypes characterized by a broad spectrum of pancreatic and extra-pancreatic clinical manifestations. Retrospective study of patients with HNF1B-MODY diagnosis followed in the Centro Hospitalar Universitário Lisboa Central (Lisbon, Portugal). Demographic data, medical history, clinical and laboratory data, follow-up and treatment procedures were obtained from electronic medical records. We found 10 patients with HNF1B variants (7 index cases). The median age at diabetes diagnosis was 28 (IQR 24) years and the median age at HNF1B-MODY diagnosis was 40.5 (IQR 23) years. Six patients were initially misclassified as type 1 and 4 as type 2 diabetes. The average time between diabetes diagnosis and the diagnosis of HNF1B-MODY was 16.5 years. Diabetes was the first manifestation in half of the cases. The other half presented with kidney malformations and chronic kidney disease at pediatric age as the first manifestation. All these patients were submitted to kidney transplantation. Long-term diabetes complications included retinopathy (410), peripheral neuropathy (210) and ischemic cardiomyopathy (110). Other extra-pancreatic manifestations included liver test alterations (410) and congenital malformation of the female reproductive tract (16). History of a first-degree relative with diabetes andor nephropathy diagnosed at a young age was present in 5 of the 7 index cases. Despite being a rare disease, HNF1B-MODY is underdiagnosed and often misclassified. It should be suspected in patients with diabetes and CKD, especially when diabetes appears at a young age, a family history is present, and nephropathy appears beforeshortly after the diagnosis of diabetes. Presence of unexplained liver disease increases the degree of suspicion for HNF1B-MODY. Early diagnosis is important to minimize complications and to allow familial screening and pre-conception genetic counseling. Trial registration not applicable due to the retrospective nature of the study, non-interventional. |
36,793,056 | Contraction of human brain vascular pericytes in response to islet amyloid polypeptide is reversed by pramlintide. | The islet amyloid polypeptide (IAPP), a pancreas-produced peptide, has beneficial functions in its monomeric form. However, IAPP aggregates, related to type 2 diabetes mellitus (T2DM), are toxic not only for the pancreas, but also for the brain. In the latter, IAPP is often found in vessels, where it is highly toxic for pericytes, mural cells that have contractile properties and regulate capillary blood flow. In the current study, we use a microvasculature model, where human brain vascular pericytes (HBVP) are co-cultured together with human cerebral microvascular endothelial cells, to demonstrate that IAPP oligomers (oIAPP) alter the morphology and contractility of HBVP. Contraction and relaxation of HBVP was verified using the vasoconstrictor sphingosine-1-phosphate (S1P) and vasodilator Y27632, where the former increased, and the latter decreased, the number of HBVP with round morphology. Increased number of round HBVP was also seen after oIAPP stimulation, and the effect was reverted by the IAPP analogue pramlintide, Y27632, and the myosin inhibitor blebbistatin. Inhibition of the IAPP receptor with the antagonist AC187 only reverted IAPP effects partially. Finally, we demonstrate by immunostaining of human brain tissue against laminin that individuals with high amount of brain IAPP levels show significantly lower capillary diameter and altered mural cell morphology compared to individuals with low brain IAPP levels. These results indicate that HBVP, in an in vitro model of microvasculature, respond morphologically to vasoconstrictors, dilators, and myosin inhibitors. They also suggest that oIAPP induces contraction of these mural cells and that pramlintide can reverse such contraction. |
36,792,995 | The prevalence of left ventricular hypertrophy associated with type-2 diabetes in Shiraz, Iran a cross-sectional study. | Left ventricular hypertrophy (LVH) is a common diagnosis in patients with cardiovascular disease (CVD). The prevalence of LVH among patients with Type-2 Diabetes Mellitus (T2DM), high blood pressure and aging is higher than the healthy population and has been independently associated with an increased risk for future cardiac event, including stroke. The aim of this study is to identify the prevalence of LVH among T2DM subjects and evaluate its association with related risk factors of CVD patients in the metropolis of Shiraz, Iran. The novelty of this study is that there has been no known published epidemiological study related to the relationship of LVH and T2DM on this unique population. This cross-sectional study was designed based on collected data of 7715 free dwelling subjects in the community-based Shiraz Cohort Heart Study (SCHS) from 2015 to 2021, ages 40-70 years. Overall, 1118 subjects with T2DM were identified in the SCHS and after exclusion criteria, 595 subjects remained eligible for study. Subjects with electrocardiography (ECG) results, which are appropriate and diagnostics tools, were evaluated for the presence of LVH. Thus, the variables related to LVH and non-LVH in subjects with diabetes were analyzed using version-22 statistical package for social sciences software program to ensure consistency, accuracy, reliability, and validity for final analysis. Based upon related variables and identifying LVH and non-LVH subjects, the relevant statistical analysis was implemented to ensure its consistency, accuracy, reliability, and validity for final analysis. Overall, the prevalence of diabetic subjects was 14.5% in the SCHS study. Furthermore, the prevalence of hypertension in the study subjects aged 40-70 years was 37.8%. The prevalence of hypertension history in T2DM study subjects for LVH compared to non-LVH was (53.7% vs. 33.7%). The prevalence of LVH among patients with T2DM as the primary target of this study was 20.7%. Analytical findings comparing both LVH and non-LVH subjects who have T2DM identified significance for variables in the older (≥ 60) mean and categorical age group (P < 0.0001), history of hypertension (P < 0.0001), mean and categorical duration of hypertension in years (P < 0.0160), status of controlled versus uncontrolled hypertension level (P < 0.0120), the mean systolic blood pressure (P < 0.0001) as well as mean duration years of T2DM and categorical duration of diabetes in years (< 0.0001 and P < 0.0060), mean fasting blood sugar (< 0.0307) and categorical status of FBS Level (mgdl) controlled and uncontrolled FBS status of controlled vs. uncontrolled FBS levels P < 0.0020). However, there were no significant findings for gender (P 0.3112), diastolic blood pressure mean (P 0.7722) and body mass index (BMI) mean and categorical BMI (P 0.2888 and P 0.4080, respectively). The prevalence of LVH in the study increases significantly among T2DM patients with hypertension, older age, years of hypertension, years of diabetes, and higher FBS. Thus, given the significant risk of diabetes and CVD, evaluation of LVH through reasonable diagnostic testing with ECG can help reduce the risk of future complications through the development of risk factor modifications and treatments guidelines. |
36,792,682 | A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes. | Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 11 to the TENS study device (n 81) and placebo (n 79). 147 (92%) randomized participants (mean SD age 59 10 years, 92 men 58%, mean SD baseline HbA |
36,792,668 | Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats. | Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats. |
36,792,418 | Variants in the Control Region of Mitochondrial Genome Associated with type 2 Diabetes in a Cohort of Mexican Mestizos. | According to the International Diabetes Federation, Mexico is seventh place in the prevalence of type 2 diabetes (T2D) worldwide. Mitochondrial DNA variant association studies in multifactorial diseases like T2D are scarce in Mexican populations. The objective of this study was to analyze the association between 18 variants in the mtDNA control region and T2D and related metabolic traits in a Mexican mestizo population from Mexico City. This study included 1001 participants divided into 477 cases with T2D and 524 healthy controls aged between 42 and 62 years and 18 mtDNA variants with frequencies >15%. Association analyses matched by age and sex showed differences in the distribution between cases and controls for variants m.315316insC (p 1.18 × 10-6), m.489T>C (p 0.009), m.16362T>C (p 0.001), and m.16519T>C (p 0.004). The associations between T2D and variants m.315316ins (OR 6.13, CI 3.42-10.97, p 1.97 × 10-6), m.489T>C (OR 1.45, CI 1.00-2.11, p 0.006), m.16362T>C (OR 2.17, CI 1.57-3.00, p 0.001), and m.16519T>C (OR 1.69, CI 1.23-2.33, p 0.006) were significant after performing logistic regression models adjusted for age, sex, and diastolic blood pressure. Metabolic traits in the control group through linear regressions, adjusted for age, sex and BMI, and corrected for multiple comparisons showed nominal association between glucose and variants m.263A>G (p <0.050), m.16183A>C (p <0.010), m.16189T>C (p <0.020), and m.16223C>T (p <0.024) triglycerides, and cholesterol and variant m.309310insC (p <0.010 and p <0.050 respectively) urea, and creatinine, and variant m.315316insC (p <0.007, and p <0.004 respectively) diastolic blood pressure and variants m.235A>G (p <0.016), m.263A>G (p <0.013), m.315316insC (p <0.043), and m.16111C>T (p <0.022). These results demonstrate a strong association between variant m.315316insC and T2D and a nominal association with T2D traits. |
36,792,219 | Pathophysiological significance in abdominal fat distribution in non-obese children with type 2 diabetes. | The aim of the study was to determine the pathogenesis of non-obese children with type 2 diabetes, and its relationship with fat distribution. The study participants included 36 obese children with type 2 diabetes (age 13.5 years, BMI 28.3, BMI percentile 91.9) and 30 non-obese children with type 2 diabetes (age 13.5 years, BMI 23.1, BMI percentile 74.0). The proportion of female participants was significantly higher in non-obese children than in obese children (73.3% vs. 41.7%, p < 0.001). Abdominal fat distribution, evaluated by subcutaneous fat (SF) area, visceral fat (VF) area, and the ratio of VF area to SF area (VS ratio), measured using computed tomography, and serum lipid levels and liver function were compared between the two groups. Non-obese children with type 2 diabetes had significantly smaller SF area and also smaller VF area than obese children with type 2 diabetes (SF area 158.3 m |
36,792,176 | A questionnaire-based survey of medical conditions in adults with Prader-Willi syndrome in Japan implications for transitional care. | Prader-Willi syndrome (PWS) is a multisystem disorder with increased mortality predominantly due to obesity-associated complications therefore, the management of obesity has been centric to therapeutic strategies for PWS. Although a multidisciplinary team approach has been successful for this purpose during childhood, it is generally difficult to implement during adulthood because of the lack of a structured transitional care program. A more detailed understanding of the current medical conditions of adults with PWS is needed to establish this program however, limited information is currently available on this issue in Japan. Accordingly, we performed a questionnaire-based survey on 425 patients with PWS. There were 162 adult patients aged 18 years or older with median body mass indexes (kgm |
36,792,168 | Non-obese or lean non-alcoholic fatty liver disease was associated with increased risk of cancer in patients with type 2 diabetes mellitus. | Risk of non-obese or lean non-alcoholic fatty liver disease (NAFLD) for cancer in patients with type 2 diabetes mellitus (T2DM) is less known. We aimed to evaluate independent associations of NAFLD, especially non-obese or lean NAFLD, and body mass index (BMI) on risks of cancer in patients with T2DM. Cross-sectional analyses of baseline information on a cohort of 233 patients with T2DM were conducted in Xiamen, China. NAFLD was identified by hepatic ultrasonography diagnosis of hepatic steatosis without excessive alcohol consumption, viral or autoimmune liver disease. Fibrosis-4 (FIB-4) score was calculated to quantify severity of hepatic fibrosis. All types of cancers were diagnosed on 19 (8.2%) patients. Prevalence of cancer was significantly higher in those with NAFLD than those without (15.5% vs 4.0%, p0.002), but were not significantly different among BMI categories (6.8%, 13.7% and 6.5% for those with underweight or normal weight (n74), overweight (n51) and obesity (n108), respectively, p0.258). With adjustment for potential confounding factors in the multivariable logistic regression models, NAFLD was significantly associated with increased risk of cancer with the adjusted OR (95% CI) of 5.969 (1.349 to 26.413, p0.019). Stratified analyses across BMI categories found similar association of NAFLD with risk of cancer for those non-obese or lean (the adjusted OR (95% CI) 17.446 (1.690 to 180.095, p0.016)) but not for those with either overweight (OR (95% CI) 11.642 (0.832 to 162.963, p0.068) or obesity (OR (95% CI) 0.917 (0.170 to 4.954, p0.920). FIB-4 score was not significantly associated with risk of cancer for all subjects or stratified across BMI categories. BMI was not significantly associated with risk of cancer for all patients or stratified by NAFLD. NAFLD, even non-obese or lean NAFLD, was independently associated with increased risk of cancer in patients with T2DM. Screening and management of NAFLD, especially for those with underweight or normal weight, should be strengthened from the perspective of improving prevention and management of cancer in patients with T2DM. |
36,791,999 | Oral empagliflozin-loaded tri-layer core-sheath fibers fabricated using tri- axial electrospinning Enhanced in vitro and in vivo antidiabetic performance. | Empagliflozin (EM) was successfully loaded in polycaprolactonepoly (L-lactic acid)polymethyl methacrylate (PCLPLAPMMA) fibers. In the rat β-cell line (BRIN-BD11), the insulin expression ratio of pancreatic β-cells was stimulated at high and low glucose by culturing with tri-layer EM-loaded fiber (EMF) for 48 h. The expression ratios of glucokinase and GLUT-2 proteins increased after EMF treatment. According to the in vitro drug release test, 97% of all drug contained in fibers was released in a controlled manner for 24 h. The pharmacokinetic test revealed that the bioavailability was improved for ∼4.8-fold with EMF treatment even in the half-dosage compared to EM-powder and blood glucose level was effectively controlled for 24 h with EMF. Oral administration of EMF exhibited a better sustainable anti-diabetic activity even in the half-dosage than EM-powder in streptozotocinnicotinamide-induced T2DM rats. The levels of GLP-1, PPAR-γ, and insulin were increased while the levels of SGLT-2 and TNF-α were decreased with EMF treatment. Also, EMF recovered the histopathological changes in the liver, pancreas, and kidney in T2DM rats and protected pancreatic β-cells. Consequently, EMF is suggested as an unprecedented and promotive treatment approach for T2DM with a higher bioavailability and better antidiabetic effect compared to conventional dosage forms. |
36,791,963 | Comorbidity profile and outcomes in patients with chronic heart failure in a Latin American country Insights from the Colombian heart failure registry (RECOLFACA). | Heart failure (HF) is usually accompanied by cardiovascular and non-cardiovascular comorbidities, which may significantly impact its prognosis. In this study we aimed to characterize the comorbidity profile and its impact in mortality in patients with HF diagnosis from the Colombian Heart Failure Registry (RECOLFACA). RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess the impact of the comorbidities in mortality. A p-value of <0.05 was considered significant. From the total 2528 patients included in the registry, 2514 patients (58% males, mean age 68 years) had information regarding comorbidity diagnoses. 2321 patients (92.3%) reported at least one comorbidity. Arterial hypertension was the most frequent individual diagnosis (72% n 1811), followed by anemia (30.1%, n 726). The most frequently observed coexisting comorbidities were coronary disease (CHD) with dyslipidemia, and chronic kidney disease (CKD) with type 2 Diabetes Mellitus (T2DM). Different patterns of comorbidity coexistence were observed when comparing HF patients by sex and left-ventricular ejection fraction (LVEF) classification. The only comorbidities that were significantly associated with mortality after multivariate adjustment were T2DM (HR 1.45. 95% CI 1.01-2.12), anemia (HR 1.48. 95% CI 1.02-2.16), and CHD (HR 1.59. 95% CI 1.09-2.33). Multiple comorbidities were frequently observed in the patients from the RECOLFACA. T2DM, anemia and CHD were significantly associated with a higher risk of mortality, highlighting the importance of promoting an optimal follow-up and control of these conditions. |
36,791,919 | Dysregulated autophagy A key player in the pathophysiology of type 2 diabetes and its complications. | Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of β-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications. |
36,791,875 | Trpc6 knockout improves behavioral dysfunction and reduces Aβ production by inhibiting CN-NFAT1 signaling in T2DM mice. | As the prevalence of diabetes and health awareness increase, type 2 diabetes mellitus -associated cognitive dysfunction is receiving increasing attention. However, the pathogenesis is not entirely understood. Transient receptor potential cation channel 6 (TRPC6) is highly correlated with intracellular Ca |
36,791,634 | Diabetes, Ramadan, and driving - Ensuring patient safety while respecting religious autonomy A qualitative study. | Hypoglycaemia due to fasting during Ramadan may affect the ability to perform complex activities among people with type 2 diabetes mellitus (T2D), but it is unclear how this affects ones ability to drive. This study aims to explore driving experiences and coping strategies to ensure safe driving among people with T2D who fast during Ramadan. We conducted an exploratory qualitative study and purposefully selected people with T2D who drove and fasted during the past Ramadan period in 2019. In-depth face-to-face interviews were conducted and transcribed verbatim. Data were analysed thematically using a constant comparative method until saturation was achieved (n 16). Two major themes were identified, namely (1) knowing oneself and (2) voluntary self-restriction. Participants described the importance of understanding how Ramadan fasting affected them and their level of alertness. As such, participants often adjusted their daily activities and tested their blood glucose levels to prevent experiencing hypoglycaemia. Other coping strategies reported include adjusting their medications and driving restrictions or driving in the mornings when they were more alert. Findings from this study shed light on participants experiences and coping mechanisms while driving during Ramadan. Given the risks and effects of hypoglycaemia among those who fast, there is a need to provide appropriate and focused patient education during Ramadan to people with T2D to ensure they can perform complex activities such as driving safely, especially in Muslim majority countries. |
36,791,500 | Hepatic oleate regulates one-carbon metabolism during high carbohydrate feeding. | Obesity is a major risk factor for type 2 diabetes, coronary heart disease, and strok. These diseases are associated with profound alterations in gene expression in metabolic tissues. Epigenetic-mediated regulation of gene expression is one mechanism through which environmental factors, such as diet, modify gene expression and disease predisposition. However, epigenetic control of gene expression in obesity and insulin resistance is not fully characterized. We discovered that liver-specific stearoyl-CoA desaturase-1 (Scd1) knockout mice (LKO) fed a high-carbohydrate low-fat diet exhibit dramatic changes in hepatic gene expression and metabolites of the folate cycle and one-carbon metabolism respectively for the synthesis of S-adenosylmethionine (SAM). LKO mice show an increased ratio of S-adenosylmethionine to S-adenosylhomocysteine, a marker for increased cellular methylation capacity. Furthermore, expression of DNA and histone methyltransferase genes is up-regulated while the mRNA and protein levels of the non-DNA methyltransferases including phosphatidylethanolamine methyltransferase (PEMT), Betaine homocysteine methyltransferase (Bhmt), and the SAM-utilizing enzymes such as glycine-N-methyltransferase (Gnmt) and guanidinoacetate methyltransferase (Gamt) are generally down-regulated. Feeding LKO mice a high carbohydrate diet supplemented with triolein, but not tristearin, and increased endogenous hepatic synthesis of oleate but not palmitoleate in Scd1 global knockout mice normalized one carbon gene expression and metabolite levels. Additionally, changes in one carbon gene expression are independent of the PGC-1α-mediated ER stress response previously reported in the LKO mice. Together, these results highlight the important role of oleate in maintaining one-carbon cycle homeostasis and point to observed changes in one-carbon metabolism as a novel mediator of the Scd1 deficiency-induced liver phenotype. |
36,791,135 | Factors predicted quality of life of people with type 2 diabetes in western Ethiopia. | Multiple factors predict the quality of life of adults with diabetes. However, the relationships of demographics, self-management practice, and support status with the quality of life of people with diabetes are unknown. Therefore, the study aimed to assess factors related with the quality of life of adults with type 2 diabetes in western Ethiopia. A hospital-based cross-sectional study involving adults with type 2 diabetes was conducted in western Ethiopia from June 02, 2020, to August 31, 2020. Convenience sampling technique was used in selecting subjects. The translated and psychometrically tested summary of diabetes self-management activities (expanded), diabetes quality of life, and diabetes care profile support scales were used in measuring self-management practice, quality of life, and support status, respectively. Data were collected via face-to-face interviews. Factors related with quality of life were examined through bivariate analysis and multivariable linear regression. In all statistical tests, P value <0.05 and confidence level that excluded zero were considered statistically significant. A total of 417 adults with type 2 diabetes participated in the study. In a multivariable linear regression, seven factors including age, male, homemakers, those separateddivorced, number of years since diabetes diagnosis, self-management practice and support needed were related with quality of life. Male patients (β 2.786, 95% CI 1.285 to 4.287, p < 0.001), homemakers (β 0.366, 95% CI 0.056 0.677, p 0.021), self-management practice (β 4.528, 95% CI 3.851 to 5.205, p < 0.001) and those who needed support from their families or peers (β 1.623, 95% CI 0.458 2.788, p 0.006) were related positively with quality of life whereas those who separated or divorced (β -1.698, 95% CI -3.371 to -0.025, p 0.047), older age (β -0.195, 95% CI -0.269 to -0.121, p < 0.001) and those who lived with diabetes for a longer duration (β -2.206, 95% CI -4.151 to -0.261, p 0.026) were related negatively with quality of life. Quality of life of people with type 2 diabetes living in western Ethiopia was predicted positively by being male, homemakers, having self-management practice, and support needed, whereas negatively influenced by old age, separation or divorce, and long diabetes life. Thus, encouraging self-management practice, and continuous family or friend support are necessary to enhance quality of life of people with type 2 diabetes. Further study should employ random sampling techniques and involve participants from multiple study settings to increase representativeness of the samples. |
36,791,131 | Telemedicine and its acceptance by patients with type 2 diabetes mellitus at a single care center during the COVID-19 emergency A cross-sectional observational study. | When Italy was placed under lockdown to contain the COVID-19 pandemic from 9 March to 18 May 2020, alternative approaches to delivering care-such as telemedicine-were promoted for patients with chronic diseases like diabetes mellitus (DM). The aim of this study was to analyze patients perception of, and satisfaction with the telehealth services offered during the COVID-19 emergency at an outpatient diabetes care unit in Italy. A cross-sectional survey was conducted on 250 patients with type 2 diabetes mellitus who regularly attended our diabetes care unit. Data were collected by means of telephone interviews, asking patients how they perceived the telehealth services, and their satisfaction with the televisit and computer-based care. A standardized questionnaire was administered there were questions answered using a five-point Likert scale, and one open-ended question. Patients demographic, anthropometric and biological data were collected from their medical records. Correlations between patients characteristics, their perception of telemedicine, and their satisfaction with the televisit were examined. Spearmans rank-order correlation coefficient ρ (rho) and Kendalls rank correlation coefficient τ (tau) were used as nonparametric measures of the strength of the association between the scores obtained for the two ordinal variables, Perception and Satisfaction, and between other clinical parameters. Principal component analysis (PCA) was also used to assess overall links between the variables. Almost half of the interviewees expressed a strongly positive perception of the medical services received, and more than 60% were very satisfied with the telehealth service provided during the COVID-19 emergency. There was a strong correlation between patients perception and satisfaction ratings (p<0.0001). Duration of disease showed a significant positive correlation with patients satisfaction with their medical care. By means of PCA, it was found that BMI correlated inversely with both perception and satisfaction. Following a qualitative analysis of patients answers to the open-ended question, contact with their specialist was important to them it was reassuring and a source of scientifically correct information about their disease and the association between COVID-19 and diabetes. Based on our telephone interviews, patients appreciated the telehealth approach and were satisfied with it, regardless of the characteristics of their disease. Telemedicine proved essential to avoid interrupting the continuity of care, and therefore had not only clinical, but also psycho-social repercussions. |
36,791,113 | How chronic conditions are understood, experienced and managed within African communities in Europe, North America and Australia A synthesis of qualitative studies. | This review focuses on the lived experiences of chronic conditions among African communities in the Global North, focusing on established immigrant communities as well as recent immigrant, refugee, and asylum-seeking communities. We conducted a systematic and narrative synthesis of qualitative studies published from inception to 2022, following a search from nine databases-MEDLINE, EMBASE, PsycINFO, Web of Science, Social Science Citation Index, Academic Search Complete, CINAHL, SCOPUS and AMED. 39 articles reporting 32 qualitative studies were included in the synthesis. The studies were conducted in 10 countries (Australia, Canada, Denmark, France, Netherlands, Norway, Sweden, Switzerland, United Kingdom, and the United States) and focused on 748 participants from 27 African countries living with eight conditions type 2 diabetes, hypertension, prostate cancer, sickle cell disease, chronic hepatitis, chronic pain, musculoskeletal orders and mental health conditions. The majority of participants believed chronic conditions to be lifelong, requiring complex interventions. Chronic illness impacted several domains of everyday life-physical, sexual, psycho-emotional, social, and economic. Participants managed their illness using biomedical management, traditional medical treatment and faith-based coping, in isolation or combination. In a number of studies, participants took therapeutic journeys-which involved navigating illness action at home and abroad, with the support of transnational therapy networks. Multi-level barriers to healthcare were reported across the majority of studies these included individual (changing food habits), social (stigma) and structural (healthcare disparities). We outline methodological and interpretive limitations, such as limited engagement with multi-ethnic and intergenerational differences. However, the studies provide an important insights on a much-ignored area that intersects healthcare for African communities in the Global North and medical pluralism on the continent they also raise important conceptual, methodological and policy challenges for national health programmes on healthcare disparities. |
36,790,935 | A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor AlphaGamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition. | A new series of analogues or derivatives of the previously reported PPARαγ dual agonist LT175 allowed the identification of ligand |
36,790,894 | Logistic regression with correlated measurement error and misclassification in covariates. | Many areas of research, such as nutritional epidemiology, may encounter measurement errors of continuous covariates and misclassification of categorical variables when modeling. It is well known that ignoring measurement errors or misclassification can lead to biased results. But most research has focused on solving these two problems separately. Addressing both measurement error and misclassification simultaneously in a single analysis is less actively studied. In this article, we propose a new correction method for a logistic regression to handle correlated error variables involved in multivariate continuous covariates and misclassification in a categorical variable simultaneously. It is not computationally intensive since a closed-form of the approximate likelihood function conditional on observed covariates is derived. The asymptotic normality of this proposed estimator is established under regularity conditions and its finite-sample performance is empirically examined by simulation studies. We apply this new estimation method to handle measurement error in some nutrients of interest and misclassification of a categorical variable named physical activity in the European Prospective Investigation into Cancer and Nutrition-InterAct Study data. Analyses show that fruit is negatively associated with type 2 diabetes for a group of women doing active physical activity, protein has positive association with type 2 diabetes for the group of less active physical activity, and actual physical activity has a greater effect on reducing the risk of type 2 diabetes than observed physical activity. |
36,790,703 | The association between road traffic noise and type 2 diabetes a systematic review and meta-analysis of cohort studies. | The association between road traffic noise and type 2 diabetes (T2DM) was inconsistent. To address this, we have synthesized available cohort studies about their association by meta-analysis. PubMed, Web of Science, EBSCO, Cochrane Library, EMBASE, and Scopus databases were searched up to July 2022. The Quality-effect model (QE) was used to incorporate the results of included studies. The possibility of publication bias was assessed by the Doi plots and Luis Furuya-Kanamori index. Sensitivity analyses included leave-one-out meta-analysis, subgroup meta-analysis, and meta-regressions. The Recommendations for Assessment, Development, and Evaluation (GRADE) guidelines were conducted to evaluate the overall quality of evidence. Eight cohort studies with 4,989,846 participants and 416,799 diabetes cases were included. Based on the fully adjusted models from 8 cohort studies (10 estimates L |
36,790,626 | Effect of periodontal therapy on insulin resistance in adults with dysglycemia and periodontitis a systematic review and meta-analysis. | This systematic review and meta-analysis aimed to address whether non-surgical periodontal therapy (NSPT) can affect insulin resistance, estimated by the homeostasis model assessment (HOMA), in adults with prediabetes or type 2 diabetes mellitus and periodontitis. Six electronic databases and the gray literature were systematically searched for interventional studies reporting NSPT effect on insulin resistance. Seven studies met the eligibility criteria to be synthesized in the qualitative analysis, six reporting change in HOMA-IR, three reporting change in HOMA-%S, and two in HOMA-β. Among them, four were pooled in a meta-analysis of standardized mean difference (SMD) of HOMA-IR comparing pre- and post-intervention values, three were pooled considering HOMA-%S as outcome, and two studies were summarized considering SMD of HOMA-%S between intervention and control groups. HOMA-β results were qualitatively synthetized. With low level of certainty, NSPT significantly reduced HOMA-IR, when compared with pre-intervention data (SMD, -0.35, 95% CI -0.63 to 0.07, p0.02). There were no significant changes in HOMA-%S or in HOMA-β scores. The level of certainty was very low and moderate, respectively. Assertions about a causal link between NSPT and insulin resistance are weak and conflicting, although our more robust results point out to the absence of effect. . Because further high-quality studies assessing the relationship between periodontitis and insulin resistance are need, the findings of the current systematic review are limited to give recommendations for clinicians. However, while identifying a lack of research in humans with T2D concerning periodontitis and insulin resistance, this study reinforces the need of multicenter well-designed randomized clinical trials. |
36,790,478 | Skeletal muscle and intermuscular adipose tissue gene expression profiling identifies new biomarkers with prognostic significance for insulin resistance progression and intervention response. | Although insulin resistance often leads to type 2 diabetes mellitus, its early stages are often unrecognised, thus reducing the probability of successful prevention and intervention. Moreover, treatment efficacy is affected by the genetics of the individual. We used gene expression profiles from a cross-sectional study to identify potential candidate genes for the prediction of diabetes risk and intervention response. Using a multivariate regression model, we linked gene expression profiles of human skeletal muscle and intermuscular adipose tissue (IMAT) to fasting glucose levels and glucose infusion rate. Based on the expression patterns of the top predictive genes, we characterised and compared individual gene expression with clinical classifications using k-nearest neighbour clustering. The predictive potential of the candidate genes identified was validated using muscle gene expression data from a longitudinal intervention study. We found that genes with a strong association with clinical measures clustered into three distinct expression patterns. Their predictive values for insulin resistance varied substantially between skeletal muscle and IMAT. Moreover, we discovered that individual gene expression-based classifications may differ from classifications based predominantly on clinical variables, indicating that participant stratification may be imprecise if only clinical variables are used for classification. Of the 15 top candidate genes, ST3GAL2, AASS, ARF1 and the transcription factor SIN3A are novel candidates for predicting a refined diabetes risk and intervention response. Our results confirm that disease progression and successful intervention depend on individual gene expression states. We anticipate that our findings may lead to a better understanding and prediction of individual diabetes risk and may help to develop individualised intervention strategies. |
36,790,356 | Network-medicine approach for the identification of genetic association of parathyroid adenoma with cardiovascular disease and type-2 diabetes. | Primary hyperparathyroidism is caused by solitary parathyroid adenomas (PTAs) in most cases (⁓85%), and it has been previously reported that PTAs are associated with cardiovascular disease (CVD) and type-2 diabetes (T2D). To understand the molecular basis of PTAs, we have investigated the genetic association amongst PTAs, CVD and T2D through an integrative network-based approach and observed a remarkable resemblance. The current study proposed to compare the PTAs-associated proteins with the overlapping proteins of CVD and T2D to determine the disease relationship. We constructed the protein-protein interaction network by integrating curated and experimentally validated interactions in humans. We found the $11$ highly clustered modules in the network, which contain a total of $13$ hub proteins (TP53, ESR1, EGFR, POTEF, MEN1, FLNA, CDKN2B, ACTB, CTNNB1, CAV1, MAPK1, G6PD and CCND1) that commonly co-exist in PTAs, CDV and T2D and reached to networks hierarchically modular organization. Additionally, we implemented a gene-set over-representation analysis over biological processes and pathways that helped to identify disease-associated pathways and prioritize target disease proteins. Moreover, we identified the respective drugs of these hub proteins. We built a bipartite network that helps decipher the drug-target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drug combinations or drug-repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs and give a synergistic effect with better outcomes. This network-based analysis opens a new horizon for more personalized treatment and drug-repurposing opportunities to investigate new targets and multi-drug treatment and may be helpful in further analysis of the mechanisms underlying PTA and associated diseases. |
36,790,138 | Antenatal dietary supplementation with myo-inositol for preventing gestational diabetes. | Gestational diabetes with onset or first recognition during pregnancy is an increasing problem worldwide. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. Myo-inositol is one of the intracellular mediators of the insulin signal and correlates with insulin sensitivity in type 2 diabetes. The potential beneficial effect of improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes. This is an update of a review first published in 2015. To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes. We searched the Cochrane Pregnancy and Childbirths Trials Register, ClinicalTrials.gov, WHO ICTRP (17 March 2022) and the reference lists of retrieved studies. We included published and unpublished randomised controlled trials (RCTs) including cluster-RCTs and conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes in pregnant women. We included studies that compared any dose of myo-inositol, alone or in a combination preparation, with no treatment, placebo or another intervention. Quasi-randomised and cross-over trials were not eligible. We excluded women with pre-existing type 1 or type 2 diabetes. Two review authors independently assessed studies for inclusion, assessed risk of bias and extracted the data. We checked the data for accuracy. We assessed the certainty of the evidence using the GRADE approach. We included seven RCTs (one conducted in Ireland, six conducted in Italy) reporting on 1319 women who were 10 weeks to 24 weeks pregnant at the start of the studies. The studies had relatively small sample sizes and the overall risk of bias was low. For the primary maternal outcomes, meta-analysis showed that myo-inositol may reduce the incidence of gestational diabetes (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.31 to 0.90 6 studies, 1140 women) and hypertensive disorders of pregnancy (RR 0.34, 95% CI 0.19 to 0.61 5 studies, 1052 women). However, the certainty of the evidence was low to very low. For the primary neonatal outcomes, only one study measured the risk of a large-for-gestational-age infant and found myo-inositol was associated with both appreciable benefit and harm (RR 1.40, 95% CI 0.65 to 3.02 1 study, 234 infants low-certainty evidence). None of the included studies reported on the other primary neonatal outcomes (perinatal mortality, mortality or morbidity composite). For the secondary maternal outcomes, we are unclear about the effect of myo-inositol on weight gain during pregnancy (mean difference (MD) -0.25 kilogram (kg), 95% CI -1.26 to 0.75 kg 4 studies, 831 women) and perineal trauma (RR 4.0, 95% CI 0.45 to 35.25 1 study, 234 women) because the evidence was assessed as being very low-certainty. Further, myo-inositol may result in little to no difference in caesarean section (RR 0.91, 95% CI 0.77 to 1.07 4 studies, 829 women low-certainty evidence). None of the included studies reported on the other secondary maternal outcomes (postnatal depression and the development of subsequent type 2 diabetes mellitus). For the secondary neonatal outcomes, meta-analysis showed no neonatal hypoglycaemia (RR 3.07, 95% CI 0.90 to 10.52 4 studies 671 infants very low-certainty evidence). However, myo-inositol may be associated with a reduction in the incidence of preterm birth (RR 0.35, 95% CI 0.17 to 0.70 4 studies 829 infants). There were insufficient data for a number of maternal and neonatal secondary outcomes, and no data were reported for any of the long-term childhood or adulthood outcomes, or for health service utilisation outcomes. Evidence from seven studies shows that antenatal dietary supplementation with myo-inositol during pregnancy may reduce the incidence of gestational diabetes, hypertensive disorders of pregnancy and preterm birth. Limited data suggest that supplementation with myo-inositol may not reduce the risk of a large-for-gestational-age infant. The current evidence is based on small studies that were not powered to detect differences in outcomes such as perinatal mortality and serious infant morbidity. Six of the included studies were conducted in Italy and one in Ireland, which raises concerns about the lack of generalisability to other settings. There is evidence of inconsistency among doses of myo-inositol, the timing of administration and study population. As a result, we downgraded the certainty of the evidence for many outcomes to low or very low certainty. Further studies for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors. Myo-inositol at different doses, frequency and timing of administration, should be compared with placebo, diet and exercise, and pharmacological interventions. Long-term follow-up should be considered and outcomes should include potential harms, including adverse effects. |
36,789,686 | ox-LDL induces autophagy-mediated apoptosis by suppressing secretagogin-regulated autophagic flux in pancreatic β-cells. | Lipotoxicity has been shown to induce the loss of functional β-cell mass and lead to type 2 diabetes, but the mechanism remains unknown. In this study, we aim to explore the role of secretagogin (SCGN) in lipotoxicity-induced β-cell injury. Our results indicate that ox-LDL treatment leads to autophagic cell death, as evidenced by decreased cell viability, aggravated cell apoptosis, and the accumulation of the p62 protein in MIN6 cells. LysoTracker Red staining, TEM and mRFP-GFP-LC3 assays demonstrate that autophagic flux is blocked in ox-LDL-treated MIN6 cells. Intriguingly, SCGN is significantly decreased in MIN6 cells under lipotoxic conditions. Additionally, siRNA-guided |
36,789,682 | Once-weekly semaglutide use in patients with type 2 diabetes real-world data from the SURE Italy observational study. | SURE Italy, a multicentre, prospective, open-label, observational, real-world study, investigated once-weekly (OW) semaglutide in patients with type 2 diabetes (T2D) in routine clinical practice. Adults with T2D and ≥1 documented HbA Of 579 patients who initiated semaglutide (FAS), 491 completed the study on treatment (EAS). Mean baseline HbA In routine clinical practice in Italy, patients with T2D treated with OW semaglutide for 30 weeks achieved clinically significant improvements in HbA |
36,789,679 | The effect of type 2 diabetes mellitus on multiple obstructive coronary artery disease. | Although type 2 diabetes mellitus (T2DM) individuals easily develop three-vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two-dimensional speckle tracking echocardiography (2-D STE) in T2DM patients with 3VD. One hundred and three consecutive patients with confirmed 3VD CAD were enrolled and divided into two groups, while 53 patients with DM and 50 patients without. The control group was composed of 30 age- and sex-matched healthy individuals. All patients underwent 2-D STE and standard echocardiograms. The durations of DM and the level of HbA1c were also recorded. Between the 3VD-DM and 3VD-non-DM groups, normal echocardiography did not reveal any appreciable differences. However, patients with 3VD-DM had significantly lower global longitudinal strain (GLS) than those with 3VD-non-DM (15.87 ± 2.51 vs.17.56 ± 2.72, p < .05) by 2-D STE strain measurement. Besides, patients whose duration of DM excess 5 years showed significant lower GLS than those with less than 5 years duration (14.25 ± 2.31 vs. 16.65 ± 1.96, p .007). However, there was no difference in GLS between the 3VD-DM patients with HbA1c ≥ 7% and HbA1c < 7%. Compared to patients with 3VD alone, those with 3VD-DM have a lower cardiac function. In 3VD-DM patients, the duration of DM is a significant factor that contributes to cardiac function deterioration, whereas, the glucose control state has limited influence. |
36,789,676 | Nonalcoholic fatty liver disease from a primary care perspective. | Nonalcoholic fatty liver disease (NAFLD) affects up to one-third of the US population. Approximately one-fifth of patients with NAFLD have nonalcoholic steatohepatitis (NASH), characterized by hepatocyte damage and inflammation with or without fibrosis. NASH leads to greater risk of liver-related complications and liver-related mortality, with the poorest outcomes seen in patients with advanced fibrosis. NASH is also associated with other metabolic comorbidities and conveys an increased risk of adverse cardiovascular outcomes and extrahepatic cancers. Despite its high prevalence, NAFLD is frequently underdiagnosed. This is a significant concern, given that early diagnosis of NAFLD is a key step in preventing progression to NASH. In this review, we describe the clinical impact of NASH from the perspective of both the clinician and the patient. In addition, we provide practical guidance on the diagnosis and management of NASH for primary care providers, who play a pivotal role in the frontline care of patients with NASH, and we use case studies to illustrate real-world scenarios encountered in the primary care setting. |
36,789,288 | A platform for phenotyping disease progression and associated longitudinal risk factors in large-scale EHRs, with application to incident diabetes complications in the UK Biobank. | Modern healthcare data reflect massive multi-level and multi-scale information collected over many years. The majority of the existing phenotyping algorithms use case-control definitions of disease. This paper aims to study the time to disease onset and progression and identify the time-varying risk factors that drive them. We developed an algorithmic approach to phenotyping the incidence of diseases by consolidating data sources from the UK Biobank (UKB), including primary care electronic health records (EHRs). We focused on defining events, event dates, and their censoring time, including relevant terms and existing phenotypes, excluding generic, rare, or semantically distant terms, forward-mapping terminology terms, and expert review. We applied our approach to phenotyping diabetes complications, including a composite cardiovascular disease (CVD) outcome, diabetic kidney disease (DKD), and diabetic retinopathy (DR), in the UKB study. We identified 49 049 participants with diabetes. Among them, 1023 had type 1 diabetes (T1D), and 40 193 had type 2 diabetes (T2D). A total of 23 833 diabetes subjects had linked primary care records. There were 3237, 3113, and 4922 patients with CVD, DKD, and DR events, respectively. The risk prediction performance for each outcome was assessed, and our results are consistent with the prediction area under the ROC (receiver operating characteristic) curve (AUC) of standard risk prediction models using cohort studies. Our publicly available pipeline and platform enable streamlined curation of incidence events, identification of time-varying risk factors underlying disease progression, and the definition of a relevant cohort for time-to-event analyses. These important steps need to be considered simultaneously to study disease progression. |
36,789,179 | Retracted Effect of Application of Treadmill Training on Metabolic Control and Vitamin D Level in Saudi Patients with Type 2 Diabetes Mellitus. | This retracts the article DOI 10.115520223059629.. |
36,789,109 | Adverse Events Related to Tirzepatide. | Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM). We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide. We performed a systematic review with meta-analysis including 5 databases (PubMed, Embase, CINAHL, Scopus, and Web of Science) for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Ten trials (6836 participants) were included. Gastrointestinal (GI) AEs were the most commonly reported AEs and were dose dependent 39% (95% CI, 35%-43%), 46% (95% CI, 42%-49%), and 49% (95% CI, 38%-60%) for the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose < 70 mgdL) was highest with tirzepatide 10 mg dose 22.6% (9.2%-39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤ 1%) across all doses of tirzepatide. Tirzepatide is associated with a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication. |
36,789,054 | Application of inulin in bread A review of technological properties and factors affecting its stability. | Due to its dual function, inulin is an important prebiotic compound in the cereal industry, especially in bread production. In other words, improving technological features and creating health properties (such as reducing the risk of type 2 diabetes, heart disease, metabolic syndrome, and osteoporosis) have led to the widespread use of this compound. Inulin has many important technological functions in bread, including its ability to interact with water, create structure, and influence rheological properties, texture, and overall acceptability of the final product. Nevertheless, bread processing conditions can influence the structural integrity of inulin and thus affect its technological efficiency. Therefore, this review article aims to investigate the technological properties and factors affecting the stability of inulin during bread processing conditions. Generally, the addition of inulin could considerably improve the technical performance of bread. However, the stability of inulin depends on the formulation components, type of fermentation, and baking process. |
36,789,048 | Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats. | Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) in disease conditions with increased oxidative stress (OS). The present study aimed to reflect on the impact of 8 weeks of a combination of UA supplementation and resistanceendurance training in old male Wistar rats having a high-fat diet andor low-dose streptozotocin-induced type 2 diabetes (HFDSTZ-induced T2D), with an emphasis on Sirtuin 1 (SIRT1)-endothelial nitric oxide synthase (eNOS) axis and OS indices in their aortic tissues. A total number of56 21-month-old male Wistar rats with HFDSTZ-induced T2D were randomized into seven groups (n eight animals per group) (1) sedentary old nondiabetic (Control C) (2) sedentary HFDSTZ-induced T2D (Diabetic D) (3) sedentary HFDSTZ-induced T2D plus UA (Diabetic Ursolic Acid DU) (4) endurance-trained HFDSTZ-induced T2D (Diabetic Endurance Training DE) (5) resistance-trained HFDSTZ-induced T2D (Diabetic Resistance Training DR) (6) endurance-trained HFDSTZ-induced T2D plus UA (Diabetic Endurance Training Ursolic Acid DEU) and (7) resistance-trained STZ-diabetic plus UA (Diabetic Resistance Training Ursolic Acid DRU) rats. The ladder-based resistance training group performed the ladder resistance training at 60% of the maximum voluntary carrying capacity (MVCC), 14-20 climbs in each session, with a one-min rest between each two trials, 5 days a week. The treadmill-based endurance exercise training protocol consisted of repeated bouts of high- and low-intensity training with 60-75% maximal running speed and 30%-40% maximal running speed in the course of 8 weeks, respectively. The animals in the supplement groups also took 500 mg of UAkg of high-fat dietday, resulting in a daily UA intake of approximately 250 mg UA per kg of body weight ratday. The resistanceendurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA), nitric oxide (NO), as well as total antioxidant capacity (TAC). It was concluded that oral 0.5% UA supplementation can prevent vascular aging biomarkers in a HFDSTZ-induced T2D model. Further studies are also required to clarify how chronic consumption of UA withwithout training protocols reverses vascular aging process. |
36,789,037 | The effect of acorn muffin consumption on glycemic indices and lipid profile in type 2 diabetic patients A randomized double-blind placebo-controlled clinical trial. | Acorn is a nutritious fruit with the reported potential of ameliorating diseases, including diabetes. This research aimed to assess the effects of acorn muffin consumption on glycemic, lipid indices, and appetite in patients with type 2 diabetes. Sixty-six subjects were dichotomized to receive either one muffin containing 10 grams of acorn flour or a placebo muffin containing white wheat flour (no bran), per day, for 8 weeks. Acorn muffin consumption improved glycated hemoglobin ( |
36,788,855 | Myocardial Infarction as an Initial Presentation of Essential Thrombocythemia With Calreticulin (CALR) Mutation (None Type 1, None Type 2). | Essential thrombocythemia (ET) is one of the classical Philadelphia-negative myeloproliferative neoplasms with different mutations that can be associated with it, like Janus kinase 2 (JAK2), myeloproliferative leukemia protein (MPL), and Calreticulin (CALR) (types 1 and 2). However, there is a lack in the literature concerning other types of CALR mutations and their clinical significance and prognosis. Here we report a 42-year-old male with type 2 diabetes who presented with an inferior ST-elevation myocardial infarction and thrombocytosis. The diagnosis of ET with CALR (neither type 1 nor type 2) was confirmed, which suggests the pathognomonic feature of this mutation. |
36,788,551 | Association of four lipid-derived indicators with the risk of developing type 2 diabetes a Chinese population-based cohort study. | Studies have reported that lipid-derived indicators are associated with type 2 diabetes (T2D) in various populations however, it is unclear which lipid-derived indicators could effectively predict T2D risk. Therefore, this study aimed to explore the association between four lipid-derived indicators and T2D risk. This was a post-hoc analysis from a large cohort that included data from 114,700 Chinese individuals aged 20 years and older from 11 cities and 32 sites. The association between four lipid-derived indicators and T2D risk was determined using Kaplan-Meier (KM) survival curves, Cox regression, and restricted cubic spline analyses. This study used receiver operating characteristic (ROC) curves for assessing the ability of four lipid-derived indicators to accurately predict the development of T2D during follow-up. This study included a total of 114,700 participants, with a mean age of 44.15. These individuals were followed up for 3.1 years, of which 2668 participants developed T2D. ROC curve analysis showed that TyG was the most robust predictor of 3-year aera under the ROC (AUC) 0.77, 95% CI 0.768, 0.772 and 5-year T2D risk (AUC 0.763, 95% CI 0.760, 0.765). In addition, sensitivity analysis showed an association between TyG and an increased incidence of T2D. The results suggest that TyG was a superior for predicting the risk of developing T2D in the general Chinese population. |
36,788,521 | Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes | To investigate the association between the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-B) with the incidence of diabetes and pre-diabetes subtypes. A total of 3101 normoglycemic people aged 20-70 years were included in the 6-year follow-up study. Multinomial logistic regression was used to calculate the incidence possibility of isolated Impaired Fasting Glucose (iIFG), isolated Impaired Glucose Tolerance (iIGT), Combined impaired fasting glucose impaired glucose tolerance (CGI), and Diabetes Mellitus (DM) per standard deviation (SD) increment in HOMA-IR and HOMA-B in the crude and multivariable model. In the multivariate model, an increase in one SD change in HOMA-IR was associated with a 43, 42, 75, and 92% increased risk of iIFG, iIGT, CGI, and DM, respectively. There was a positive correlation between the increase in HOMA-B and the incidence of iIGT however, after adjusting the results for metabolic syndrome components, it was inversely correlated with the incidence of iIFG Odds Ratio 0.86(0.75-0.99). HOMA-IR is positively correlated with diabetes and pre-diabetes subtypes incidence, and HOMA-B is inversely correlated with the incidence of iIFG but positively correlated with iIGT incidence. However, none of these alone is a good criterion for predicting diabetes and pre-diabetes. |
36,788,517 | The effects of aqueous and ethanolic extracts of Rheum ribes on insulin-resistance and apolipoproteins in patients with type 2 diabetes mellitus a randomized controlled trial. | Previous studies have shown that Rheum ribes (R. ribes) could be effective in controlling the blood glucose levels. This study was conducted to determine the effects of R. ribes supplementation on glycemic indices and apolipoproteins in patients with type 2 diabetes mellitus (T2DM). In the present randomized double-blind controlled trial, 60 type 2 diabetic patients aged 30-60 years with a body mass index (BMI) of 20-30 kgm There was a significant decrease in the serum levels of insulin in AG and EG groups (P 0.003 and P 0.001, respectively), HOMA-IR (P 0.01 and P 0.001, respectively), HOMA-B (P 0.002 and P 0.001, respectively), ApoB (P 0.006 and P 0.03, respectively), ApoBApoA1 ratio (P 0.016 and P 0.04, respectively). However, a significant increase in ApoA1 (P 0.08 and P 0.05, respectively) with no significant changes in blood glucose, at the end of study compared to beginning values, were observed. None of the variables showed a significant change in PG. At the end of the study while there were significant differences in insulin (P 0.04), HOMA-IR (P 0.03), HOMA-B (P 0.01), ApoB (P 0.02), and ApoBApoA1 ratio (P 0.03) among the groups but ApoA1 had no significant change. Consumption of R. ribes intake could have beneficial effects on insulin resistance and apolipoproteins in type 2 diabetic patients. (Registered at en.irct.ir, identification number IRCT201410142709N31). |
36,788,497 | Estimating incidence of type 1 and type 2 diabetes using prevalence data the SEARCH for Diabetes in Youth study. | Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. We used age-, sex-, and raceethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings. |
36,788,467 | Reproducibility and determinants of the metabolic responses during a mixed-meal tolerance test. | The aim of this study was to assess the reproducibility and physiological determinants of mixed-meal tolerance tests (MMTTs) on glucose and insulin responses. While inpatients on a weight-maintaining diet, 894 individuals (574 with normal and 267 with impaired glucose regulation and 53 with type 2 diabetes T2D) underwent 9-hour MMTTs (breakfast and lunch 30% weight-maintaining diet each 40% carbohydrate, 40% fat, and 20% protein). Totalincremental areas under the curve (AUCiAUC) were calculated from MMTT plasma glucoseinsulin concentrations. Acute insulin response (AIR) was quantified by intravenous glucose tolerance test and insulin action (M) via hyperinsulinemic-euglycemic clamp. A subset had repeat MMTTs (median follow-up 1.4 years). In individuals without T2D, for breakfast-versus-lunch reproducibility of glucose, AUCs were moderate (intraclass correlation coefficients ICCs 0.44-0.61), and iAUCs were poor (ICCs < 0.15). For repeated MMTTs, reproducibility of AUCiAUCs was low (ICCs 0.11-0.36). For insulin, AUC reproducibility was high (ICCs > 0.70), and iAUCs were moderate (ICCs 0.64-0.71). For repeated MMTTs, ICC AUCiAUCs were 0.34 to 0.54. In those with T2D, ICC glucose AUCiAUCs were >0.80 and >0.50, respectively, and for insulin were <0.40. For repeated MMTTs, ICC glucoseinsulin AUCiAUCs were moderate. Glucose AUCs associated with MAIR (partial Rs < -0.25), and insulin AUCs negativelypositively associated with MAIR (partial Rs -0.510.24). Reproducibility of glucoseinsulin responses to MMTTs varied by subtraction of fasting values, glucose status, and time. Insulin secretion and action explained 20% of MMTT responses. The substantial variability in MMTT response requires consideration in studies using MMTT outcomes. |
36,787,983 | Glomerular Hyperfiltration Predicts Kidney Function Decline and Mortality in Type 1 and Type 2 Diabetes A 21-Year Longitudinal Study. | To evaluate the prognostic value of glomerular hyperfiltration on long-term kidney-related outcomes and mortality in patients with diabetes. We retrospectively analyzed 21-year longitudinal data from 314 patients with long-standing type 1 or type 2 diabetes. Glomerular hyperfiltration was identified based on the age- and sex-specific distribution of measured glomerular filtration rate (mGFR) by 99mTc-DTPA dynamic renal scintigraphy. The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease (ESKD), or cardiorenal death. The kidney-specific outcome was a composite of doubling of serum creatinine, ESKD, or renal death. Over a median of 21.0 years, the primary composite outcome occurred in 25 (39.7%), 24 (38.1%), and 46 (24.5%) participants with high mGFR (H-mGFR) (n 63), low mGFR (L-mGFR) (n 63), or normal mGFR (N-mGFR) (n 188), respectively. Compared with N-mGFR, the hazard ratio (HR) for the primary composite outcome was 2.09 (95% CI 1.25-3.49) in H-mGFR and 1.81 (1.05-3.16) in L-mGFR. The HR for the kidney-specific composite outcome was 4.95 (2.21-11.09) in H-mGFR and 3.81 (1.70-8.56) in L-mGFR. The HRs for doubling of serum creatinine and cardiorenal death were 4.86 (2.18-10.90) and 2.18 (1.24-3.83) in H-mGFR and 4.04 (1.77-9.20) and 2.26 (1.27-4.01) in L-mGFR, respectively. Glomerular hyperfiltration, similar to hypofiltration, increases the combined risk of worsening kidney function and mortality from cardiovascular or renal causes in patients with diabetes. These findings encourage the active screening of these patients to optimize risk stratification and treatment of subclinical kidney disease. |
36,787,959 | Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study. | Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class-specific PUFA concentrations with type 2 diabetes risk. In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 182, 203, and 204 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (182n-6), dihomo-γ-linolenic acid (203n-6), and arachidonic acid (204n-6). The Δ-5 desaturase (D5D) activity was estimated as the 204203 ratio. Associations with diabetes were estimated with Cox proportional hazards models. Higher concentrations of 182 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio HR per 1 SD 0.53 95% CI 0.23-1.26) and monoacylglycerols (HR 0.59 0.38-0.92). Higher concentrations of 203 in phospholipid classes phosphatidylcholines (HR 1.63 1.23-2.14), phosphatidylethanolamines (HR 1.87 1.32-2.65), and phosphatidylinositol (HR 1.40 1.05-1.87) free fatty acids (HR 1.44 1.10-1.90) and cholesteryl esters (HR 1.47 1.09-1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 204 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class. |
36,787,958 | Association and Interaction of Genetics and Area-Level Socioeconomic Factors on the Prevalence of Type 2 Diabetes and Obesity. | Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity. Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T2D and BMI and 2) area-level socioeconomic risk (educational attainment) measures. The primary analysis included 26,737 participants of European genetic ancestry in MGBB with replication in UKB (N 223,843), as well as in participants of non-European ancestry (MGBB N 3,468 UKB N 7,459). The area-level socioeconomic measure most strongly associated with both T2D and obesity was percent without a college degree, and associations with disease prevalence were independent of genetic risk (P < 0.001 for each). Moving from lowest to highest quintiles of combined genetic and socioeconomic burden more than tripled T2D (3.1% to 22.2%) and obesity (20.9% to 69.0%) prevalence. Favorable socioeconomic risk was associated with lower disease prevalence, even in those with highest genetic risk (T2D 13.0% vs. 22.2%, obesity 53.6% vs. 69.0% in lowest vs. highest socioeconomic risk quintiles). Additive effects of genetic and socioeconomic factors accounted for 13.2% and 16.7% of T2D and obesity prevalence, respectively, explained by these models. Findings were replicated in independent European and non-European ancestral populations. Genetic and socioeconomic factors significantly interact to increase risk of T2D and obesity. Favorable area-level socioeconomic status was associated with an almost 50% lower T2D prevalence in those with high genetic risk. |
36,787,937 | Effects of Intensive Systolic Blood Pressure Lowering on End-Stage Kidney Disease and Kidney Function Decline in Adults With Type 2 Diabetes Mellitus and Cardiovascular Risk Factors A Post Hoc Analysis of ACCORD-BP and SPRINT. | To determine the effects of intensive systolic blood pressure (SBP) lowering on the risk of major adverse kidney outcomes in people with type 2 diabetes mellitus (T2DM) andor prediabetes and cardiovascular risk factors. This post hoc ACCORD-BP subgroup analysis included participants in the standard glucose-lowering arm with cardiovascular risk factors required for SPRINT eligibility. Cox proportional hazards regression models compared the hazard for the composite of dialysis, kidney transplant, sustained estimated glomerular filtration rate (eGFR) <15 mLmin1.73 m2, serum creatinine >3.3 mgdL, or a sustained eGFR decline ≥57% between the intensive (<120 mmHg) and standard (<140 mmHg) SBP-lowering arms. The study cohort included 1,966 SPRINT-eligible ACCORD-BP participants (40% women) with a mean age of 63 years. The mean SBP achieved after randomization was 120 ± 14 and 134 ± 15 mmHg in the intensive and standard arms, respectively. The kidney composite outcome occurred at a rate of 9.5 and 7.2 events per 1,000 person-years in the intensive and standard BP arms (hazard ratio HR 1.35 95% CI 0.85-2.14 P 0.20). Intensive SBP lowering did not affect the risk of moderately (HR 0.96 95% CI 0.76-1.20) or severely (HR 0.92 95% CI 0.66-1.28) increased albuminuria. Including SPRINT participants with prediabetes in the cohort did not change the overall results. This post hoc subgroup analysis suggests that intensive SBP lowering does not increase the risk of major adverse kidney events in individuals with T2DM and cardiovascular risk factors. |
36,787,923 | Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes. | The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D). Among participants with incident diabetes identified in the Nurses Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy LCDS (ULCDS) were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality. Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality. |
36,787,903 | Safety and Efficacy of the Omnipod 5 Automated Insulin Delivery System in Adults With Type 2 Diabetes From Injections to Hybrid Closed-Loop Therapy. | Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial. Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmolmol). Participants completed 2 weeks of CGM-sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mgdL and <54 mgdL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mgdL). Participants (N 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmolmol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mgdL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mgdL remained low during both ST and AID (median interquartile range 0.0% 0.00%, 0.06% vs. 0.00% 0.00%, 0.03% P 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmolmol P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID. Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population. |
36,787,895 | Proinsulin-to-C-Peptide Ratio as a Marker of β-Cell Function in African American and European American Adults. | The primary purpose of the current study was to test the hypothesis that the proinsulin-to-C-peptide (PI-to-CP) ratio, as an index of proinsulin secretion, would be higher and associated with indices of β-cell function in African American adults relative to European American adults without type 2 diabetes. Participants were 114 African American and European American adult men and women. A 2-h oral glucose tolerance test was conducted to measure glucose, insulin, C-peptide, and proinsulin and derive indices of β-cell response to glucose. The Matsuda index was calculated as a measure of insulin sensitivity. The disposition index (DI), the product of insulin sensitivity and β-cell response, was calculated for each phase of β-cell responsivity. Pearson correlations were used to investigate the relationship of the PI-to-CP ratio with each phase of beta symbol-cell response (basal, Φb dynamic, Φd static, Φs total, Φtot), disposition indices (DId, DIs, DItot), and insulin sensitivity. Multiple linear regression analysis was used to evaluate independent contributions of race, BMI, and glucose tolerance status on PI-to-CP levels before and after adjustment for insulin sensitivity. African American participants had higher fasting and 2-h PI-to-CP ratios. The fasting PI-to-CP ratio was positively associated with Φb, and the fasting PI-to-CP ratio and 2-h PI-to-CP ratio were inversely associated with DId and insulin sensitivity only in African American participants. The PI-to-CP ratio could be useful in identifying African American individuals at highest risk for β-cell dysfunction and ultimately type 2 diabetes. |
36,787,839 | Association of Community Walkability and Glycemic Control Among Pregnant Individuals with Pregestational Diabetes. | Neighborhood walkability is a community-level social determinant of health that measures whether people who live in a neighborhood walk as a mode of transportation. Whether neighborhood walkability is associated with glycemic control among pregnant individuals with pregestational diabetes remains to be defined. To evaluate the association between community-level neighborhood walkability and glycemic control as measured by hemoglobin A1c (A1c) among pregnant individuals with pregestational diabetes. This was a retrospective analysis of pregnant individuals with pregestational diabetes enrolled in an integrated prenatal and diabetes care program from 2012-2016. Participant addresses were geocoded and linked at the census tract level. The exposure was community walkability, defined by the U.S. Environmental Protection Agency (EPA) National Walkability Index (score range 1-20), which incorporates intersection density (design), proximity to transit stops (distance), and a mix of employment and household types (diversity). Individuals from neighborhoods that were the most walkable (score 15.26-20.0) were compared with those from neighborhoods that were less walkable (score <15.26) defined per national EPA recommendations. The outcomes were glycemic control, including A1c <6.0% and <6.5%, measured both in early and late pregnancy, and mean change in A1c across pregnancy. Modified Poisson regression and linear regression were used, respectively, and adjusted for maternal age, body mass index at delivery, parity, race and ethnicity as a social determinant of health, insurance status, baseline A1c, gestational age at A1c measurement in early and late pregnancy, and diabetes type. Among 417 pregnant individuals (33% type 1, 67% type 2 diabetes), 10% were living in the most walkable communities. All 417 individuals underwent A1c assessment in early pregnancy (median gestational age 9.7 weeks IQR 7.4, 14.1), and 376 underwent repeat A1c in late pregnancy (median gestational age 30.4 weeks, IQR 27.8, 33.6). Pregnant individuals living in the most walkable communities were more likely to have an A1c <6.0% in early pregnancy (15% vs. 8% aRR 1.46 95% CI 1.00-2.16), as well as an A1c <6.5% in late pregnancy compared to those living in less walkable communities (13% vs. 9% aRR 1.33 95% CI 1.08-1.63). For individuals living in the most walkable communities, the median A1c was 7.5 (IQR 6.0, 9.4) in early pregnancy and 5.9 (IQR 5.4, 6.4) in late pregnancy. For those living in less walkable communities, the median A1c was 7.3 (IQR 6.2, 9.2) in early pregnancy and 6.2 (IQR 5.6, 7.1) in late pregnancy. Change in A1c across pregnancy was not associated with walkability. Pregnant individuals with pregestational diabetes living in more walkable communities had better glycemic control in both early and late pregnancy. Whether community-level interventions to enhance neighborhood walkability can improve glycemic control in pregnancy requires further study. |
36,787,689 | Predicting type 2 diabetes prevalence for people with severe mental illness in a multi-ethnic East London population. | Prevalence of type two diabetes mellitus (T2DM) in people with severe mental illness (SMI) is 2-3 times higher than in general population. Predictive modelling has advanced greatly in the past decade, and it is important to apply cutting-edge methods to vulnerable groups. However, few T2DM prediction models account for the presence of mental illness, and none seemed to have been developed specifically for people with SMI. Therefore, we aimed to develop and internally validate a T2DM prevalence model for people with SMI. We utilised a large cross-sectional sample representative of a multi-ethnic population from London (674,000 adults) 10,159 people with SMI formed our analytical sample (1,513 T2DM cases). We fitted a linear logistic regression and XGBoost as stand-alone models and as a stacked ensemble. Age, sex, body mass index, ethnicity, area-based deprivation, past hypertension, cardiovascular diseases, prescribed antipsychotics, and SMI illness were the predictors. Logistic regression performed well while detecting T2DM presence for people with SMI area under the receiver operator curve (ROC-AUC) was 0.83 (95 % CI 0.79-0.87). XGBoost and LR-XGBoost ensemble performed equally well, ROC-AUC 0.83 (95 % CI 0.79-0.87), indicating a negligible contribution of non-linear terms to predictive power. Ethnicity was the most important predictor after age. We demonstrated how the derived models can be utilised and estimated a 2.14 % (95 %CI 2.03 %-2.24 %) increase in T2DM prevalence in East London SMI population in 20 years time, driven by the projected demographic changes. Primary care data, the setting where prediction models could be most fruitfully used, provide enough information for well-performing T2DM prevalence models for people with SMI. We demonstrated how thorough internal cross-validation of an ensemble of a linear and machine-learning model can quantify the predictive value of non-linearity in the data. |
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