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The analysis of risk factors for diabetic kidney disease progression a single-centre and cross-sectional experiment in Shanghai.

To identify the risk factors for diabetic kidney disease (DKD) development, especially the difference between patients with different courses. 791 patients were considered to be eligible and were enrolled in the cross-sectional study from Shanghai Tongren Hospital Inpatient Department. 36 variables were initially screened by univariate analysis. The risk factors affecting progression of DKD were determined by logistics regression analysis. Subgroups were grouped according to the course of diabetes disease, and multivariate logistics regression analysis was performed to find out the different risk factors in two subgroups. Finally, the receiver operating characteristics curve is used to verify the result. The logistic regression model indicated age (OR1.020, p0.017, 95% CI 1.004 to 1.040), systolic blood pressure (OR1.013, p0.006, 95% CI 1.004 to 1.022), waist circumference (OR1.021, p0.015, 95% CI 1.004 to 1.038), white blood cells (WBC, OR1.185, p0.001, 95% CI 1.085 to 1.295) and triglycerides (TG, OR1.110, p0.047, 95% CI 1.001 to 1.230) were risk factors for DKD, while free triiodothyronine (fT3, OR0.711, p0.011, 95% CI 0.547 to 0.926) was a protective factor for DKD in patients with type 2 diabetes mellitus (T2DM). Subgroup analysis revealed that in patients with a short duration of diabetes (<8 years), WBC (OR1.306, p<0.001, 95% CI 1.157 to 1.475) and TG (OR1.188, p0.033, 95% CI 1.014 to 1.393) were risk factors for DKD,fT3 (OR0.544, p0.002, 95% CI 0.367 to 0.804) was a protective factor for DKD whereas for patients with disease course more than 8 years, age (OR1.026, Pp0.012, 95%CI95% CI 1.006- to 1.048) was identified as the only risk factor for DKD and fT3 (OR0.036, Pp0.017, 95%CI95% CI 0.439- to 0.922) was a protective factor for DKD. The focus of attention should especially be on patients with a prolonged course of T2DM, and those with comorbid hypertension and hypertriglyceridaemia waist phenotype. More potential clinical indexes such as thyroid function and inflammatory indicators might be considered as early warning factors for DKD in T2DM. Women should pay attention to controlling inflammation and TGs, and men should strictly control blood pressure. Avoiding abdominal obesity in both men and women will bring great benefits.

Effects of message framing on self-management behaviour among patients with type 2 diabetes a randomised controlled trial protocol.

Accumulating evidence has indicated successful diabetes health education can potentially help to improve blood sugar levels in people with diabetes. However, with a rapid rise in the number of people with diabetes cases and the increasing burden on healthcare, it is often difficult for healthcare providers to find suitable time to provide health education to meet their needs. Thus, more novel and effective ways are needed to conduct education. The message frame provides a new perspective for implementation of a more effective health education in the form of changing information presentation, and the same objective content is described in either positive or negative language or outcomes. Gain framing emphasises the positive consequences of adhering to useful recommendations, while loss framing highlights the negative consequences of the non-adherence. The purpose of our research is to potentially explore the effectiveness of diabetes education based on message framing on the self-management behaviour. A single-blind, three-arm randomised controlled trial involving 84 participants will be conducted. The participants will be assigned into three groups randomly in a 111 ratio and will receive 12-week intervention. Patients in group 1 will be provided gain framing education videos about the self-management skills for type 2 diabetes, patients in group 2 will be given education videos based on loss framing and patients in group 3 will receive education with no specific message framing. The primary outcome is self-management behaviour. The secondary outcomes will be self-efficacy, patient activation, diabetes-related knowledge and attitude, quality of life and blood glucose level. All outcomes will be measured at baseline and 12 weeks. This study was approved by the Ethics Committee of School of Nursing, Jilin University (No. 2020101501). The research results will be published in peer-reviewed publications and presented in international conferences. ChiCTR 2100045772 Pre-results.

Reversal of Diabesity Normalization of Insulin Release Curve in Association with Reversal of Non-Alcoholic Fatty Liver Disease.

Type 2 diabetes with obesity is regarded as an incurable, progressive disease with many complications. The hypothesis was tested that glycated haemoglobin (HbA1c) and the insulin release curve can be restored by traceable systematic methods. 122 people with diabesity were investigated before and after three and 6 months of traceable systematic management methods. Basal body mass index (BMI), fatty liver, HbA1c, and insulin release curve were measured. After 3 months of traceable systematic management, BMI decreased from 30.76 ± 0.48 to 21.86 ± 0.09 kgm2 (p < 0.001) and remained stable during the last 3 months (21.82 ± 0.09 kgm2 at 6 months). Colour Doppler ultrasound showed non-alcoholic fatty liver disease (NAFLD) in all diabesity participants at baseline. At 3 months, only one participant had low-grade fatty liver, and fatty liver was reversed in other participants (p < 0.001). The number and grade of fatty liver at 6 months were the same as at 3 months. Fasting plasma glucose decreased and continued to decrease thereafter (p < 0.001). Two-hour postprandial plasma glucose decreased and continued to decline until 6 months (p < 0.001). HbA1c also decreased and maintained this level at 6 months. At baseline, the peak value of insulin release was 1,141.09 ± 43.02 pmolL at 2 h after meals, and the early phase of insulin secretion was lost. After 3 months of management, the insulin concentration was 621.62 ± 19.32 pmolL at 2 h after meals. After 6 months, the value decreased, and the early phase of insulin secretion recovered. Normalization of the insulin release curve in type 2 diabetes was achieved by traceable systematic methods. This was associated with recovery from NAFLD. Diabesity is reversible by traceable systematic management.

The Role of Melatonin in Chronic Kidney Disease and Its Associated Risk Factors A New Tool in Our Arsenal

The increasing incidence of chronic kidney disease (CKD), as a consequence of the high prevalence of arterial hypertension and type 2 diabetes mellitus (T2DM), warrants the need for developing effective treatment approaches. In this regard, the pineal gland-derived hormone melatonin may represent an appealing treatment approach of CKD and its associated risk factors. Targeting the adverse pathophysiology surrounding CKD and its associated risk factors has been the concept of pharmacologic treatment developed for its management. This review article aimed to present the role of melatonin in this direction, by providing an overview of melatonins physiology followed by its effect as a therapeutic agent in arterial hypertension and T2DM. Melatonin, the primary darkness hormone, possesses pleiotropic mechanisms of action which may have important implications in various pathologic states since its receptors are situated across various organ systems. As a treatment tool in arterial hypertension, melatonin may be efficacious in reducing both daytime and nocturnal blood pressure by influencing endothelial function, oxidative stress, the autonomic nervous system, and the renin-angiotensin system. Melatonin may also increase insulin sensitivity and β-cell function. However, late meal intake may be detrimental in glucose regulation, as consumption close to melatonin peak concentrations may induce hyperglycemia and insulin resistance. This finding may explain the inconsistent glycose regulation achieved with melatonin in clinical trials and meta-analyses. Additionally, the presence of genetic variants to melatonin receptor 2 may predispose to T2DM development. Finally, we present the available preclinical evidence supporting melatonins efficacy in ameliorating CKDs pathophysiology since melatonin supplementation has not been adequately explored in patients with CKD. The combined use of stem cells with melatonin is an appealing therapeutic approach which ought to be assessed further.

IL-18 Serum Levels in Patients with Obesity, Prediabetes and Newly Diagnosed Type 2 Diabetes.

Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions. To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. This study included 387 Caucasians divided into four groups healthy controls, obese subjects without carbohydrate issues, prediabetic patients, and recently discovered type 2 diabetics. Subject with body mass index ≥30kgm2 and glycemic disorders showed significantly high levels of IL-18 (249.77 ± 89.96 pgml 259.01 ± 95.70 pgml and 340.98 ± 127.65 pgml) compared with that of the control group (219.47 ± 110.53 pgml, p < 0.05). IL-18 also had significant positive associations with some anthropometric parameters, liver enzymes, fasting, post-load glucose, insulin, uric acid, and triglycerides while negative with HDL. The circulating IL-18 levels for differentiating subjects with carbohydrate disturbances and those with metabolic syndrome were determined by ROC analysis. The AUC for the disturbances of the carbohydrate metabolism was 0.597 (p 0.001 95% CI 0.539 - 0.654) and for MS AUC was 0.581 (p 0.021 95 % CI 0.516 - 0.647). Our data indicate that as the levels of IL-18 are increased the carbohydrate tolerance is deteriorated. However, the significance of IL-18 in the progression of diabetes mellitus and subsequent consequences requires further exploration.

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health.

The incretin hormone system is the target of multiple type 2 diabetes mellitus (T2DM) treatments because defects in this system play major roles in the pathogenesis of diabetes. Currently, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended for patients with atherosclerotic cardiovascular (CV) disease and those at high risk for atherosclerotic CV disease. In addition to the favorable CV effects, GLP-1 RAs also provide robust lowering of hemoglobin A1c and weight. Although these factors make GLP-1 RAs attractive options for T2DM, the currently available agents have no effect on glucose-dependent insulinotropic polypeptide (GIP). Patients with T2DM are known to have GIP defect which is significant due to its profound insulinotropic effects. Tirzepatide is a novel incretin agent currently recently approved by the Food and Drug Administration for the treatment of T2DM. This first-in-class agent serves as a coagonist for both the GLP-1 and GIP receptors. In this review, we report on the pharmacologic mechanism of GLP-1, GIP, and coagonist effects on the cardiometabolic system. In addition, we review the glycemic lowering, weight loss effects, and other cardiometabolic outcomes of tirzepatide based on phase 2 and 3 data. The safety profile of tirzepatide is consistent across all phase 3 trials. The most common adverse effects are gastrointestinal symptoms, but they generally have a low risk for discontinuation. Overall, preliminary data suggest that tirzepatide is an efficacious and safe agent for the treatment of T2DM.

Fu Brick Tea Manages HFDSTZ-Induced Type 2 Diabetes by Regulating the Gut Microbiota and Activating the IRS1PI3KAkt Signaling Pathway.

The antidiabetic effects of Fu brick tea aqueous extract (FTE) and its underlying molecular mechanism in type 2 diabetes mellitus (T2DM) mice were investigated. FTE treatment significantly relieved dyslipidemia, insulin resistance (IR), and hepatic oxidative stress caused by T2DM. FTE also ameliorated the T2DM-induced gut dysbiosis by decreasing the

Prevalence and factors associated with inappropriate anti- diabetic medication therapy among type 2 diabetes mellitus patients at the medical and surgical wards of Mbarara Regional Referral Hospital, Uganda.

Inappropriate Anti-diabetic Medication Therapy (IADT) refers to a drug-related problem and includes ineffective drug therapy, unnecessary drug therapy, dosage too high, and dosage too low. This study aimed to determine the prevalence and factors associated with IADT among T2DM patients at Mbarara Regional Referral Hospital, Uganda (MRRH). A prospective cross-sectional study was conducted at the medical and surgical wards of MRRH from November 2021 to January 2022. One hundred and thirty-eight adult patients aged 18 years and above, with T2DM, were recruited using consecutive sampling. Patient file reviews and interviewer-administered questionnaire was used for data collection. The data were entered into and analyzed using SPSS version 25. Descriptive analysis was employed to describe the population and determine the prevalence of IADT. Types of IADTs were identified using Cipolles DRP classification tool. A univariate and multivariate logistic regression analysis was used to identify factors significantly associated with IADT. The P-value of < 0.05 was considered statistically significant at 95% confidence interval. A total of 138 hospitalized T2DM patients were studied. Eighty (58.0%) were females, and 70 (50.7%) were ≥ 60 years of age. Out of a total of 138 participants, 97 experienced at least one IADT, with an estimated prevalence of 70.3%. Dosage too high (29.2%) and dosage too low (27.9%) were the most common type of IADTs. Age ≥ 60 years (AOR, 8.44 95% CI, 2.09-10.90 P-value 0.003), T2DM duration of < 1 year (AOR, 0.37 95% CI, 0.11-0.35 P-value 0.019), and HbA1c of < 7% (AOR, 9.97 95% CI, 2.34-13.57 P-value 0.002) were found to be factors significantly associated with the occurrence of IADTs. The overall prevalence of inappropriate anti-diabetic medication therapy among T2DM patients admitted to medical and surgical wards of MRRH was 70.3%. The most common type of IADT in this study was dosage too high, accounting for almost one-third followed by dosage too low accounting for a quarter of total IADTs. Age greater or equal to 60 years, T2DM duration of < 1 year, and HbA1c of < 7% during the current admission were found to be factors significantly associated with the occurrence of IADTs in hospitalized T2DM patients.

Pharmacological analysis of Empagliflozin Acting through the CaMKII pathway in type 2 diabetes and acute cardiovascular events.

Type 2 diabetes mellitus is a high-risk factor for acute cardiovascular events. Some reports show that Empagliflozin has a protective effect on cardiovascular events and diabetes mellitus, and Empagliflozin can act on the CaMKII pathway. However, the specific gene of action is not precise. Therefore, this study investigated the target genes of Empagliflozin by integrated gene analysis and molecular docking method to provide a theoretical basis for further elucidating the mechanism of action of Empagliflozin. In this study, we obtained 12 datasets from GEO, divided into experimental and validation groups, with a total of 376 samples. We then integrated CaMKII pathway-related genes from OMIM, NCBI, and genecards databases. We then intersected them with the differential genes we obtained to obtain 5 common genes and performed functional enrichment analysis. We then performed group comparisons in the validation set, and we obtained 2 clinically significant genes. Then we performed group comparison in the validation set, and we obtained 2 clinically significant genes, followed by molecular docking analysis with pymol, autodock software. We obtained molecular docking models for the 2 genes. In this study, we obtained CaMK2G and PPP1CA, genes associated with the CaMKII pathway and type 2 diabetes and acute cardiovascular events, by integrative gene analysis and validated their expression in the relevant dataset. We also derived that Empagliflozin acts on amino acid TRP-125 of CaMK2G gene and GLN-249 ASP-210 ASP-208 of PPP1CA through CaMKII pathway, thus acting on type 2 diabetes and acute cardiovascular events by molecular docking technique.

Renoprotective effects of empagliflozin in type 1 and type 2 models of diabetic nephropathy superimposed with hypertension.

Diabetes, hypertension, and aging are major contributors to cardiovascular and chronic kidney disease (CKD). Sodiumglucose cotransporter 2 (SGLT2) inhibitors have become a preferred treatment for type II diabetic patients since they have cardiorenal protective effects. However, most elderly diabetic patients also have hypertension, and the effects of SGLT2 inhibitors have not been studied in hypertensive diabetic patients or animal models. The present study examined if controlling hyperglycemia with empagliflozin, or given in combination with lisinopril, slows the progression of renal injury in hypertensive diabetic rats. Studies were performed using hypertensive streptozotocin-induced type 1 diabetic Dahl salt-sensitive (STZ-SS) rats and in deoxycorticosterone-salt hypertensive type 2 diabetic nephropathy (T2DN) rats. Administration of empagliflozin alone or in combination with lisinopril reduced blood glucose, proteinuria, glomerular injury, and renal fibrosis in STZ-SS rats without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Blood pressure and renal hypertrophy were also reduced in rats treated with empagliflozin and lisinopril. Administration of empagliflozin alone or in combination with lisinopril lowered blood glucose, glomerulosclerosis, and renal fibrosis but had no effect on blood pressure, kidney weight, or proteinuria in hypertensive T2DN rats. RBF was not altered in any of the treatment groups, and GFR was elevated in empagliflozin-treated hypertensive T2DN rats. These results indicate that empagliflozin is highly effective in controlling blood glucose levels and slows the progression of renal injury in both hypertensive type 1 and type 2 diabetic rats, especially when given in combination with lisinopril to lower blood pressure.

Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy a glucose-independent effect through AMPK signaling.

Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs that possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of the selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), to ameliorate streptozotocin-induced DPN in rats with insight into its precise signaling mechanism. Rats were allocated into four groups, where control animals received vehicle daily for 2 weeks. In the remaining groups, DPN was elicited by single intraperitoneal injections of freshly prepared streptozotocin and nicotinamide (52.5 and 50 mgkg, respectively). Then EMPA (3 mgkgp.o.) was given to two groups either alone or accompanied with the AMPK inhibitor dorsomorphin (0.2 mgkgi.p.). Despite the non-significant anti-hyperglycemic effect, EMPA improved sciatic nerve histopathological alterations, scoring, myelination, nerve fibers count, and nerve conduction velocity. Moreover, EMPA alleviated responses to different nociceptive stimuli along with improved motor coordination. EMPA modulated ATPAMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK12 and consequently p-NF-κB p65 as well as its downstream mediators (TNF-α and IL-1β), besides enhancing SOD activity and lowering MDA content. Moreover, EMPA downregulated mTOR and stimulated ULK1 as well as beclin-1. Likewise, EMPA reduced miR-21 that enhanced RECK, reducing MMP-2 and -9 contents. EMPAs beneficial effects were almost abolished by dorsomorphin administration. In conclusion, EMPA displayed a protective effect against DPN independently from its anti-hyperglycemic effect, probably via modulating the AMPK pathway to modulate oxidative and inflammatory burden, extracellular matrix remodeling, and autophagy.

Practical Guidance on Basal Insulin Initiation and Titration in Asia A Delphi-Based Consensus.

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM.

Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women a biomarker of cardiometabolic risk.

Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Considering the roles of these proteins according to localization, the eHSP70-to-iHSP70 ratio (H-index) has been proposed as a biomarker for HSR. We, therefore, evaluated whether this biomarker is associated with glycemic and inflammatory status in postmenopausal women. In this transversal study, 36 postmenopausal women were grouped according to fasting glycemia status as either the control group (normoglycemic, ≤ 99 mgdL) or DM2 (prediabetic and diabetic, glycemia ≥ 100 mgdL). DM2 group showed higher triglycerideglucose (TyG) index and plasma atherogenic index (PAI), both of which are indicators of cardiometabolic risk. In addition, we found that the eHSP70-to-iHSP70 ratio (plasmaperipheral blood mononuclear cells-PBMC ratio) was higher in the DM2 group, compared with the control group. Furthermore, blood leukocyte and glycemia levels were positively correlated with the eHSP70-to-iHSP70 ratio in women that presented H-index values above 1.0 (a.u.). Taken together, our results highlight the eHSP70-to-iHSP70 ratio as a biomarker of altered HSR in DM2 postmenopausal women.

Proteomic analysis of infected root canals with apical periodontitis in patients with type 2 diabetes mellitus A cross-sectional study.

This study aimed to quantitatively and qualitatively determine the proteomic profile of apical periodontitis (AP) in type 2 diabetes mellitus (T2DM) patients in comparison with systemically noncompromised patients and to correlate the protein expression of both groups with their biological functions. The sample consisted of 18 patients with asymptomatic AP divided into two groups according to the presence of T2DM diabetic group-patients with T2DM (n 9) and control group-systemically healthy patients (n 9). After sample collection, the root canal samples were prepared for proteomic analysis using reverse-phase liquid chromatography-mass spectrometry. Label-free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in protein expression between groups were calculated using t-test (p < .05). Biological functions were analysed using the Homo sapiens UniProt database. A total of 727 human proteins were identified in all samples. Among them, 124 proteins common to both groups were quantified, out of which 65 proteins from the diabetic group showed significant differences compared with the control 43 upregulated (p < .05) and 22 downregulated (p < .05) proteins. No significant differences in protein expression were seen for the remaining 59 proteins (p > .05). Most proteins with differences in expression were related to immuneinflammatory response. Neutrophil gelatinase-associated lipocalin, Plastin-2, Lactotransferrin and 13 isoforms of immunoglobulins were upregulated. In contrast, Protein S100-A8, Protein S100-A9, Histone H2B, Neutrophil defensin 1, Neutrophil defensin 3 and Prolactin-inducible protein were downregulated. Quantitative differences were demonstrated in the expression of proteins common to diabetic and control groups, mainly related to immune response, oxidative stress, apoptosis and proteolysis. These findings revealed biological pathways that provide the basis to support clinical findings on the relationship between AP and T2DM.

Prescribing costs of hypoglycaemic agents and associations with metabolic control in Wales a national analysis of primary care data.

There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control. We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmolmol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation. There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median £289 (IQR 247-343) range £31.1-£1713. Higher total expenditure was not associated with improved glycaemic control B Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications.

Type 2 diabetes mellitus and sleep characteristics a population-based study in Tumbes, Peru.

To determine if there is an association between type 2 diabetes mellitus (T2DM) and some sleep characteristics duration, sleep difficulties and quality, in a population aged between 30 and 69 years in Tumbes. Cross-sectional study. The outcomes were sleep difficulty (sometimes almost never vs. frequently), sleep duration (normal, short, and long), and sleep quality (good and bad). The exposure of interest was the presence of T2DM assessed using the glucose tolerance test (without T2DM, with T2DM but without previous diagnosis, and with T2DM and with previous diagnosis). Poisson regression models were used to report prevalence ratio (PR) and 95% confidence intervals (95%CI). A total of 1604 subjects were analyzed and the mean age was 48.2 years 50.3% were women, 71 (4.4%) had T2DM without a previous diagnosis, and 105 (6.5%) had T2DM with a previous diagnosis. Regarding sleep characteristics, 12.0% had short sleep, 8.2% had long sleep, 3.7% had sleep difficulties, and 19.5% presented poor sleep quality. In a multivariable model, T2DM with previous diagnosis was associated with sleep difficulty (PR 2.20 95%CI 1.13 - 4.27) and bad sleep quality (PR 1.40 95%CI 1.05 - 1.92) compared to those without T2DM. Individuals with previous diagnosis of T2DM had greater probability of presenting sleep difficulties and poor sleep quality. These results suggest the need to evaluate periodically the sleep characteristics of patients with T2DM. Determinar si existe asociación entre la presencia de diabetes mellitus tipo 2 (DM2) y la duración, dificultad para dormir, y calidad de sueño, en sujetos de 30 a 69 años en Tumbes. Estudio transversal analítico. Las variables dependientes fueron dificultad para dormir (a vecescasi nunca y frecuentemente), duración del sueño (normal, corto y prolongado) y calidad del sueño (buena y mala). La variable independiente fue la presencia de DM2 evaluada usando la prueba de tolerancia oral a la glucosa (no DM2, con DM2 y sin diagnóstico previo, y con DM2 y diagnóstico previo). Se usó modelos de regresión de Poisson para reportar razones de prevalencia (RP) e intervalos de confianza al 95% (IC 95%). Se analizaron 1604 individuos, con una edad media de 48,2 años 50,3% fueron mujeres 71 (4,4%) tenían DM2 sin diagnóstico previo y 105 (6,5%) tenían DM2 con diagnóstico previo. Según las características del sueño, 12,0% presentó sueño corto y 8,2% presentó sueño prolongado 3,7% reportó dificultad para dormir, y 19,5% tuvo mala calidad de sueño. En el modelo multivariable, tener DM2 con diagnóstico previo estuvo asociado con dificultad para dormir (RP 2,20 IC 95% 1,13-4,27) y mala calidad de sueño (RP 1,40 IC 95% 1,05-1,92) comparado con aquellos sin DM2. Los individuos con DM2 que tenían diagnóstico previo tuvieron mayor probabilidad de presentar dificultad para dormir y mala calidad de sueño. Nuestros resultados sugieren la necesidad de evaluar en forma periódica las características del sueño en pacientes con DM2.

Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM COVID-19 patients. We found a poorer prognosis for the DM COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

GC gene polymorphisms found with type 2 diabetes and low vitamin D status among rural Chinese in Henan province.

Accumulating evidence suggests that vitamin D may be involved in the pathogenesis of type 2 diabetes (T2D). Group-specific component (GC) gene is the most important transporter of vitamin D and plays a regulatory role in vitamin D metabolism. We aimed to evaluate the association of GC gene polymorphisms with T2D susceptibility and vitamin D status in the Chinese rural population. A total of 1372 subjects were eligible in this cross-sectional study. Three SNPs of the GC gene (rs7041, rs4588, and rs2282679) were genotyped by TaqMan probe assays. Logistic regression and Kruskal-Wallis one-way analysis were performed to determine the possible risk genotype for T2D and vitamin D metabolite concentrations, respectively. The serum 25-hydroxyvitamin D3 25(OH)D3 and vitamin D binding protein (DBP) concentrations were significantly lower in the T2D group than the non-T2D group. GG genotype carriers of rs7041 (T>G) were more likely to have T2D compared with AA carriers (OR2.00, 95% CI 1.19-3.37). Variants of rs4588 (C>A) and rs2282679 (A>C) were associated with a lower risk of T2D under the dominant inheritance model (OR0.65, 95% CI 0.48-0.88 OR0.66, 95% CI 0.49-0.90, respectively). We further found that non-T2D subjects with the AA genotype of rs4588 had significantly higher 25(OH)D3 concentrations than the CC genotype (p0.022). In contrast, the T2D cases with the CC genotype of rs2282679 had lower DBP concentrations compared to the AA genotype (p0.020). Our study indicates a potential role for GC gene polymorphisms in T2D susceptibility and vitamin D metabolite concentrations in the Chinese rural population.

Thiamin and riboflavin status with related enzyme activities in pulmonary tuberculosis with diabetes mellitus in Shandong province of China.

Poor nutritional status is a common finding in pulmonary tuberculosis (TB) patients with and without type 2 diabetes mellitus (T2DM), thiamin (VB-1) and riboflavin (VB-2) are coenzymes important for the activation of many enzymes involved in improving nutritional status. We aimed to investigate enzymatic activities and the associations between VB-1 and VB-2, and their relations to nutritional status in TB and TBT2DM patients. This was a cross-sectional study that prospectively enrolled TB 40 patients with or without T2DM respectively from the Chest Hospital of Qingdao and 76 healthy controls with similar age and gender distributions were recruited from the medical center of the affiliated hospital of Qingdao Medical College. The erythrocyte transketolase activation coefficient (ETKac, for VB-1 deficiency), the glutathione reductase activation coefficient (EGRac, for VB-2 deficiency), and metabolic enzyme activities were analyzed. VB-1 and VB-2 deficiency rates were higher, and enzyme activities were lower in TB and TBT2DM relative to control group. ETKac and EGRac were negatively correlated with enzyme activities, either with body mass index (BMI), while enzyme activities were positively associated with BMI. VB-1 and VB-2 concentrations were lower in TB patients with or without T2DM relative to controls, with concomitant reductions in the activity levels of key metabolic enzymes. Significant correlations were observed between VB-1 and VB-2 concentrations and the activity of these metabolic enzymes, they all correlated with nutrition status. VB-1 and VB-2 concentrations may thus impact metabolic enzyme activity and thereby influence nutritional status.

Fibrosis Risk in Nonalcoholic Fatty Liver Disease Is Related to Chronic Kidney Disease in Older Type 2 Diabetes Patients.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, associated with fibrosis and an increased risk of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This work aimed to investigate the association of NAFLD fibrosis with the development of CKD in aged patients with T2DM. This cross-sectional study enrolled 13 915 participants. A further 1734 individuals who had been followed annually for 5 years comprised the retrospective cohort study. Noninvasive markers, NAFLD fibrosis score (NFS), and fibrosis index based on 4 factors (FIB-4) were applied to determine NAFLD fibrosis risk. In the cross-sectional study, there was an additive interaction for NAFLD with increased risk of fibrosis and T2DM on CKD incidence. Logistic regression demonstrated that as NAFLD fibrosis risk progressed from low to intermediate and high, there was a stepwise increase in CKD in patients with NAFLD, T2DM, and those with coexistent NAFLD and T2DM when stratified by diabetes and fibrosis stage. FIB-4 had a much higher odds ratio (OR) value than NFS for prediction of CKD incidence. In the cohort study, individuals were grouped according to FIB-4 and NFS. Cox regression analysis showed that FIB-4 intermediate risk (hazard ratio HR 1.268 95% CI, 1.056-1.521) and high risk (HR 2.516 95% CI, 1.970-3.214) were significant predictors of CKD progression. When NFS was applied, only high risk was a significant predictor. NAFLD with an increased risk of fibrosis and presence of T2DM had an additive interaction on CKD incidence. Increased risk of NAFLD fibrosis was closely associated with CKD incidence and progression in aged T2DM patients. FIB-4 outperformed NFS as a noninvasive means to predict CKD development.

Exploring the link between Parkinsons disease and type 2 diabetes mellitus in Drosophila.

Parkinsons disease (PD) is the second most common neurodegenerative disease. Diabetes mellitus (DM) is a metabolic disease characterized by high levels of glucose in blood. Recent epidemiological studies have highlighted the link between both diseases it is even considered that DM might be a risk factor for PD. To further investigate the likely relation of these diseases, we have used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1), and diet-induced Drosophila and mouse type 2 DM (T2DM) models, together with human neuron-like cells. T2DM models were obtained by feeding flies with a high sugar-containing medium, and mice with a high fat diet. Our results showed that both fly models exhibit common phenotypes such as alterations in carbohydrate homeostasis, mitochondrial dysfunction or motor defects, among others. In addition, we demonstrated that T2DM might be a risk factor of developing PD since our diet-induced fly and mouse T2DM models present DA neuron dysfunction, a hallmark of PD. We also confirmed that neurodegeneration is caused by increased glucose levels, which has detrimental effects in human neuron-like cells by triggering apoptosis and leading to cell death. Besides, the observed phenotypes were exacerbated in DJ-1β mutants cultured in the high sugar medium, indicating that DJ-1 might have a role in carbohydrate homeostasis. Finally, we have confirmed that metformin, an antidiabetic drug, is a potential candidate for PD treatment and that it could prevent PD onset in T2DM model flies. This result supports antidiabetic compounds as promising PD therapeutics.

Risk of incident type 2 diabetes in patients with psoriatic arthritis A systematic review and meta-analysis of cohort studies.

To determine the risk of type 2 diabetes among patients with psoriatic arthritis (PsA). Electronic database searches of PubMed, EMBASE and Cochrane Library were performed from inception to June 2020 and updated in May 2022. Cohort studies were included if they reported hazard ratios (HR) or relative risks with 95% confidence interval (CI) of incident diabetes in patients with PsA compared with non-rheumatic populations. Pooled HR and 95% CI were calculated using a DerSimonian and Laird method random-effects model. A total of 5 studies comprising 37 811 PsA patients with 174 825 patient-years and 476 838 non-rheumatic controls with 2 945 358 patient-years were identified and included in our data analysis. During the follow-up, 2335 and 23 035 incident diabetes were observed in PsA and non-rheumatic control groups, corresponding to a crude incidence rate of 13.4 and 7.8 per 1000 patient-years, respectively. The pooled age- and gender-adjusted, and fully adjusted HR of incident diabetes in patients with PsA compared with non-rheumatic populations were 1.54 (95% CI 1.43-1.67, I Our study indicates a 38% increase in the risk of type 2 diabetes among patients with PsA, with an incidence rate of 13.4 per 1000 patients-years. These findings suggest the awareness of managing diabetes with careful screening of PsA patients in daily practice.

Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).

Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L 95% CI, 8.4 to 3.6 Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. URL httpswww. gov Unique identifier NCT04049045.

Dietary patterns derived by reduced rank regression and non-communicable disease risk.

Most current nutrition policies and dietary recommendations still reflect decades of research addressing the mechanism of action or health risks of individual nutrients. Yet, most high-income countries including the UK are far from reaching the dietary intakes which are recommended for good health. Food-based dietary patterns (DPs) can help target specific combinations of foods that are associated with disease risk, recognising the coexistence of multiple nutrients within foods and their potential synergistic effects. Reduced rank regression (RRR) has emerged as a useful exploratory approach which uses

The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease.

Despite strong preclinical data supporting the use of mineralocorticoid receptor antagonists (MRAs) to provide cardiorenal protection in rodent models of diabetes, the clinical evidence of their utility in treating chronic kidney disease (CKD) has been limited. Two major clinical trials (FIDELIO-DKD and FIGARO-DKD) including more than 13,000 patients with albuminuric CKD and Type 2 diabetes randomized to placebo or finerenone (MRA) have recently provided exciting results showing a significant risk reduction for kidney and cardiovascular outcomes. In this review, we will summarize the major findings of these trials, together with post-hoc and pooled analyses that have allowed evaluation of the efficacy and safety of finerenone across the spectrum of CKD, revealing significant protective effects of finerenone against kidney failure, new-onset atrial fibrillation or flutter, new-onset heart failure, cardiovascular death, and first and total heart-failure hospitalizations. Moreover, we will discuss the current evidence that supports the combined use of MRAs with sodium-glucose co-transporter-2 inhibitors, either by providing an additive cardiorenal benefit or by decreasing the risk of hyperkalemia. Although the mechanisms of protection by finerenone have only been partially explored in patients, rodent studies have shed light on its anti-inflammatory and anti-fibrotic effects in models of kidney disease, which is one of the main drivers for testing the efficacy of finerenone in non-diabetic CKD patients in the ongoing FIND-CKD trial.

Anti-diabetic effect of banana peel dietary fibers on type 2 diabetic mellitus mice induced by streptozotocin and high-sugar and high-fat diet.

We used a high-fat diet (HFD) and streptozotocin (STZ) to induce type 2 diabetic mellitus (T2DM) mice and evaluated the effect of banana peel dietary fibers (BP-DFs) as potential hypoglycemic agents. After 5 weeks of intervention with banana peel dietary fibers (BP-DFs), food intake was reduced, body weight was increased, blood lipids and glucose were reduced, fasting insulin and GLP-1 levels were increased, and liver and pancreatic tissue damage was reduced. Banana peel soluble dietary fiber (BP-SDF) has the most significant effect. The results of fecal microbiota analysis showed that BP-DFs could ameliorates gut microbiome dysbiosis, and all three types of dietary fibers have obvious effects. The results of fecal short-chain fatty acids (SCFAs) showed that the content of fecal SCFAs was increased after BP-DFs dietary intervention, and BP-SDF had the most obvious effect. RT-PCR experiment results show that BP-DFs can up-regulate the mRNA expression levels of PI3K, AKT, IRS-1, and FOXO1 in the liver of diabetic mice, which indicates that BD-DFs may play a role in improving insulin resistance and insulin signal transduction via the IRSPI3KAKT pathway, improving insulin resistance and insulin signal transduction. Our research may be extended to BP-DFs, especially BP-SDF, as the basis for potential dietary intervention to prevent or treat type 2 diabetic mellitus. This work supports future research studies of the anti-diabetic properties of BP-SDF in humans. PRACTICAL APPLICATIONS Diabetes can lead to a variety of complications that have a huge impact on health. Dietary fiber may help in lowering blood sugar. Our experimental results showed that banana peel dietary fibers have the effect of reducing food intake, blood sugar, improving liver and pancreas function, increasing the abundance of intestinal flora, and improving the IRSPI3KAKT pathway in T2DM mice. Therefore, this study could provide a theoretical basis for the development of functional foods with banana peel dietary fiber.

Drug repositioning in drug discovery of T2DM and repositioning potential of antidiabetic agents.

Repositioning or repurposing drugs account for a substantial part of entering approval pipeline drugs, which indicates that drug repositioning has huge market potential and value. Computational technologies such as machine learning methods have accelerated the process of drug repositioning in the last few decades years. The repositioning potential of type 2 diabetes mellitus (T2DM) drugs for various diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases have been widely studied. Hence, the related summary about repurposing antidiabetic drugs is of great significance. In this review, we focus on the machine learning methods for the development of new T2DM drugs and give an overview of the repurposing potential of the existing antidiabetic agents.

The Role of Thiazolidinediones in the Amelioration of Nonalcoholic Fatty Liver Disease A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is a broad term encompassing hepatic steatosis and non-alcoholic steatohepatitis (NASH), a form of chronic hepatitis. This may, unfortunately, lead to terminal complications like cirrhosis and hepatocellular carcinoma (HCC). NAFLD is strongly associated with obesity, type 2 diabetes (T2DM), hypertension, and metabolic syndrome. The growing prevalence of NAFLD, its associated conditions, and its complications are alarming. The insulin sensitizer group thiazolidinediones has shown some therapeutic benefits in this condition. This systematic review is intended to focus on the clinical efficacy of this group in patients with NAFLD, employing PubMed, Google Scholar, and the Cochrane Library as databases. We discovered 10 randomized control trials (RCTs nine involving pioglitazone and one involving rosiglitazone) involving 887 participants. All studies varied in duration from 6 to 24 months. Most of the involved trials had a small number of participants, and the intrinsic quality of the studies was mixed. Pioglitazone consistently improved histological parameters and normalized liver transaminases, although evidence supporting the benefits of other drugs in this class was minimal. Thiazolidinediones, particularly pioglitazone, have proven efficacious in patients with NAFLDNASH. However, more extensive trials need to be carried out to investigate this drug classs benefits further. Unfortunately, this drug has attendant side effects like weight gain and fractures, limiting its widespread use hence, careful selection for likely candidates is imperative.

Diffusion Tensor Imaging Evaluates Effects of Acupoint Injection at Zusanli (ST36) for Type 2 Diabetic Peripheral Neuropathy.

BACKGROUND Acupoint injection is a therapeutic method that combines acupuncture and Western medicine and shows good curative effects for neuropathies. This study aimed to explore the efficacy of acupoint injection for treating diabetic peripheral neuropathy (DPN) by magnetic resonance neuroimaging (MRN). MATERIAL AND METHODS Forty patients with DPN were randomly divided into an acupoint injection group (AI n20) and intramuscular injection group (MI n20). The AI group received an acupoint injection of mecobalamin at acupoint Zusanli (S36) the MI group received intramuscular injection of mecobalamin. The curative effect was evaluated by the Toronto Clinical Neuropathy Score and diffusion tensor imaging (DTI). RESULTS The neuropathy scores of both groups decreased from baseline (AI 9.31±2.36 MI 9.34±2.54) to after the 2-week treatment (AI 7.12±1.87 MI 7.86±2.11) the differences were not significant. The fractional anisotropy (FA) value showed significant differences on the common peroneal nerve (AI 0.36±0.04 MI 0.31±0.05 P<0.05) and tibial nerve (AI 0.38±0.07 MI 0.34±0.06 P<0.05) after treatment. Likewise, apparent diffusion coefficient (ADC) values between groups showed significant differences for the common peroneal nerve (AI 1.44±0.17×10⁻³ mm²s MI 1.61±0.20×10⁻³ mm²s P<0.05) and tibial nerve (AI 1.54±0.22×10-3 mm²s MI 1.60±0.17 10⁻³ mm²s P<0.05). CONCLUSIONS Patients with DPN showed lower nerve FA and higher ADC in DTI-MRN. The acupoint injection of mecobalamin could treat DPN and repair the damaged nerves, which was shown by elevated FA and lowered ADC. Our study provides clinical evidence for the application of acupoint injection therapy and the evaluation of DPN by MRN.

The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes.

Type 2 diabetes mellitus is a complex progressive disease leading to chronic hyperglycemia due to insulin resistance and pancreatic beta-cell failure. Intensification of treatment regimens is often necessary due to the overall decline in insulin secretion. Unfortunately, many patients are unable to achieve optimal glycemic control despite the standard of care and thus may be classified as treatment resistant. Newer pharmacotherapeutic agents, either injectable or oral, such as Glucagon-like-peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose Cotransporter-2 (SGLT2) inhibitors are, herein, described. These agents can be used as single agents or fixed combinations that reduce glycemia while lessening the risk for hypoglycemia and renal and cardiovascular diseases. If individualized target HbA1c is not obtained despite diet, lifestyle, and metformin therapy, then additional oral and injectable therapies should be considered. This may include newer agents such as GLP-1RA and SGLT2 inhibitors alone or in combination that provide renal protection and reduce cardiovascular and hypoglycemic risks. These newer agents have substantial potential for lowering HbA1c through differing but complementary mechanisms. Use of new insulin analogs with GLP-1RA preparations either alone or in fixed-ratio combinations, such as glarginelixisenatide and degludecliraglutide, can also reduce the multiple drug adherence burden while improving glycemic control.

Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations.

Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for equitable deployment of PRS to clinical practice that benefits global populations. We integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases 57,694 controls), four Black cohorts (5137 cases 9657 controls), and the Taiwan Biobank (4570 cases 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts. The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined. The top 2% of the PRS distribution can identify individuals with an approximately 2.5-4.5-fold of increase in T2D risk, which corresponds to the increased risk of T2D for first-degree relatives. The post hoc ancestry adjustment method eliminated major distributional differences in the PRS across ancestries without compromising its predictive performance. By integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors a nationwide cohort study.

Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 11 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i hazard ratio (HR)0.90 95% confidential interval (CI) 0.84-0.96 P 0.0028 or GLP-1RA HR 0.74 95% CI 0.63-0.88 P 0.0007 treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users HR 1.01 95% CI 0.86-1.19 P 0.8980. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction 0.02). Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis.

Osteoarthritis (OA) is the most common musculoskeletal disease, and it has a complex pathology and unknown pathogenesis. Chondrocyte ferroptosis is closely associated with the development of OA. As a common drug administered for the treatment of type 2 diabetes, metformin (Met) is known to inhibit the development of ferroptosis. However, its therapeutic effect in OA remains unknown. The present study aimed to explore the effects of Met on cartilage and subchondral bone in a mouse OA model and to explore the potential underlying mechanisms. A mouse OA model was induced using destabilization of the medial meniscus (DMM) surgery, chondrocyte ferroptosis was induced using an intra-articular injection of Erastin, and Met (200 mgkgday) was intragastrically administered for 8 weeks after surgery. HE and Safranin O‑fast green staining were used to evaluate cartilage degeneration, and μ‑computed tomography was used to evaluate changes in subchondral bone microarchitecture. Moreover, immunohistochemical staining was performed to detect mechanistic metalloproteinases 13, type II collagen, glutathione peroxidase 4, acyl-CoA synthetase long-chain family member 4, solute carrier family 7 member 11 and p53. Runt-associated transcription factor 2 and CD31 were detected using immunofluorescent staining. Met protected articular cartilage and reversed the abnormal expression of ferroptosis-related proteins in the chondrocytes of DMM mice. Moreover, intra-articular injection of Erastin induced ferroptosis in mouse chondrocytes, and Met eliminated the ferroptosis effects induced by Erastin and protected articular cartilage. In addition, the results of the present study demonstrated that Met alleviated the microstructural changes of subchondral osteosclerosis and reduced heterotypic angiogenesis in DMM mice. Met alleviates the pathological changes of OA by inhibiting ferroptosis in OA chondrocytes, alleviating subchondral sclerosis and reducing abnormal angiogenesis in subchondral bone in advanced OA.

Putative protective effects of sodium-glucose cotransporter 2 inhibitors on atrial fibrillation through risk factor modulation and off-target actions potential mechanisms and future directions.

Atrial fibrillation, the most common cardiac arrhythmia, results in substantial morbidity and mortality related to its increased risks of stroke, heart failure, and impaired cognitive function. The incidence and prevalence of atrial fibrillation in the general population is rising, making atrial fibrillation treatment and management of its risk factors highly relevant clinical targets. One well-studied risk factor for the development of atrial fibrillation is diabetes mellitus. Inhibitors of sodium-glucose cotransporter 2 (SGLT2), common medications used to treat diabetes mellitus, have been observed to decrease the incidence of atrial fibrillation. This review discusses the SGLT2 and its role in glucose homeostasis, molecules inhibiting the transporter, possible physiological mechanisms responsible for the decreased incident atrial fibrillation in patients treated with SGLT2 inhibitors and proposes mechanistic studies to further our understanding of the biological processes involved.

An Early Assessment of the Real-World Treatment Patterns of Type 2 Diabetes A Comparison to the 2018 ADAEASD Consensus Report Recommendations.

Using the American Diabetes Association (ADA) Hyperglycemic Pharmacotherapy Guidelines for type 2 diabetes, we evaluated the medication use patterns in real-world patients with type 2 diabetes in the USA. Health care claims among patients with type 2 diabetes were analyzed (IBM A large proportion of patients belonged to multiple clinical groups this was more common in the Medicare cohort. Each clinical group in the Commercial cohort had a substantially higher RTUR than in the Medicare cohort. However, no clinical group achieved > 40% RTUR. The RTUR was the highest in the CKD and obesity groups in the Commercial cohort and in the hypo and obesity groups in the Medicare cohort, but lowest in hypo and HF groups in the Commercial and Medicare cohorts, respectively. Prevalence of guideline-aligned treatment use in 2019 was low, particularly since many patients fit into multiple risk groups with established treatment benefits.

National handbook for the prevention and control of diabetes in primary care (2022).

National handbook for the prevention and control of diabetes in primary care (2022) is made for the use in combination with the national guidelines for the prevention and control of diabetes in primary care (2022). It provides detailed information and supplementary for the contents involved in the guidelines. 《国家基层糖尿病防治管理手册（2022）》是为配合《国家基层糖尿病防治管理指南（2022）》使用而制定，对该指南涉及的推荐内容和知识进行详细说明和补充。.

To promote the integration of prevention and treatment for the whole-course management of diabetes interpretation of the national guideline for the prevention and control of diabetes in primary care (2022).

《国家基层糖尿病防治管理指南（2022）》在2018版基础上，基于卫生行政部门的管理要求和新近发布的相关领域研究证据，主要在糖尿病的管理要求、筛查、诊断、治疗、低血糖的识别和处理及慢性并发症检查等方面进行了更新。此外，首次增加了糖尿病中医药防治部分，为基层医务人员提供更全面的指导。.

Effect of electroacupuncture on renal vascular microcirculation in diabetic mice based on in vivo two-photon microscopy imaging.

To investigate the protective effect of electroacupuncture (EA) at Zusanli(ST36)and Weiwanxiashu(EX-B3) on capillary function around the renal tubule and renal tubule structure in diabetic mice based on two-photon microscopy (TPM) imaging, so as to providing visualizable evidence for the regulatory effect of EA on diabetic renal vascular microcirculation. Spontaneous type Ⅱ diabetes mellitus mice (dbdb) were employed for this study. Twenty dbdb mice were randomly divided into model group ( Compared with the control group, the proportion of mice with decreased body mass in the model group was increased, accounting for 40%, while that in the control group was 0% and fasting blood glucose, urine production and water consumption were significantly increased in the model group ( EA at ST36 and EX-B3 can ameliorate renal vascular microcirculation disorder to relieve the renal structure damage and improve renal function in diabetes mice.

When and What to Eat A Scoping Review of Health Outcomes of Fasting in Conjunction with a Low-Carbohydrate Diet.

Over the last several decades, there has been an increase in chronic diseases such as neurodegenerative, inflammatory, cardiovascular diseases, and cancers. Two eating patterns, a low-carbohydrate diet, and fasting have been researched independently over this period and found to be beneficial in reducing many of these chronic diseases detrimental effects. However, there have been limited studies about the synergy of these eating patterns. This current scoping review aims to explore the evidence of the health outcomes of using a low-carbohydrate diet in conjunction with fasting. Four databases were searched, and fifteen articles were found that fit the inclusion criteria. The articles reported positive effects of combining the two eating patterns for type 2 diabetes, cardiovascular disease, inflammatory conditions, and weight reduction and maintenance. Low-carbohydrate diet and fasting together provide synergy in decreasing metabolic syndrome (as the key causes of chronic illnesses), such as insulin levels, fasting glucose, blood pressure, triglycerides, and regulating lipid profile. Due to the paucity of research, further high-quality studies are needed to substantiate this evidence.

Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes systematic review and pairwise and network meta-analysis of randomised controlled trials.

To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases. Systematic review and pairwise and network meta-analysis. PubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021. Randomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs. Composite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases. Two reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals. A total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43) risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79) risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists. Dipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice. PROSPERO CRD42021271647.

Rifampicin resistance and risk factors associated with significantly lower recovery rates after two-stage revision in patients with prosthetic joint infection.

Rifampicin plays a key role in the management of prosthetic joint infections (PJIs) however, the emergence of rifampicin resistance is associated with less favourable clinical outcomes. The purpose of this study was to investigate the impact of rifampicin resistance and other patient-related factors on recovery rates among patients with PJI undergoing two-stage revision. We reviewed medical records and microbiology reports of 73 patients (41 males and 32 females) undergoing two-stage revision due to PJI between 2017 and 2019. Patient-specific data, comorbidities and the antibiotic resistance of microbiological isolates were registered. Forty-eight patients had hip, 22 had knee, 2 had shoulder and 1 had elbow joint infection. Obtained data were statistically analysed with a logistic regression model. Rifampicin-sensitive organism was isolated in 53 cases (72.6%). Recovery rate was 92.5% in the sensitive and 60.0% in the resistant group. We observed that rifampicin resistance significantly reduced the probability of recovery. Furthermore, in the rifampicin-sensitive group, the probability of recovery decreased with advancing age with a significant drop above the age of 60 years. The effect of age is negligible in the rifampicin-resistant group. We also found that type 2 diabetes mellitus has a negative effect on recovery. Coagulase-negative Staphylococci were predominant in the rifampicin-sensitive (50% of the isolates) and Gram-negative rods in the resistant group (40%). Rifampicin resistance was associated with lower recovery rates among patients undergoing two-stage revision due to PJI. Higher age and type 2 diabetes mellitus had negative impact on clinical outcome.

Exploring therapeutic mechanisms of San-Huang-Tang in nonalcoholic fatty liver disease through network pharmacology and experimental validation.

San-Huang-Tang (SHT), a traditional Chinese medicine (TCM) formula, has been clinically used to treat obesity and type 2 diabetes mellitus. Recently it has proved that SHT have a good effect on non-alcoholic fatty liver disease (NAFLD). Our study was designed to investigate the therapeutic mechanisms of the SHT against NAFLD. The data of SHT were obtained through network pharmacology platform and validated experimentally in vivo and in vitro. The candidate targets of SHT were predicted by network pharmacological analysis and crucial targets were chosen by the protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto encyclopedia of genes and Genomes (KEGG) were applied to analyze the NAFLD-related signaling pathways affected by SHT, and then the analysis results were verified with molecular biological experiments in vivo and in vitro. Molecules were screened with network pharmacological analysis, and then the improvement of insulin resistance of NAFLD mice was measured by IPITTs and IPGTTs. Through series of molecular experiments, it is revealed that SHT could increase the transcription of insulin receptor (INSR) and insulin receptor substrate (IRS1), and enhance the phosphorylation of both threonine protein kinase (AKT) and forkhead box O1 (FoxO1). Screened by bioinformatics and verified by experiments in vivo and in vitro, SHT could contribute to NAFLD by affecting insulin resistance via activating INSRIRS1AKTFoxO1 pathway. Our research findings provide not only an experimental basis for the therapeutic effect of SHT but also a new target against NAFLD.

Effects of an exercise-based lifestyle intervention on systemic markers of oxidative stress and advanced glycation endproducts in persons with type 2 diabetes Secondary analysis of a randomised clinical trial.

This secondary analysis aimed to investigate the effects of a 12 months intensive exercise-based lifestyle intervention on systemic markers of oxidative stress in persons with type 2 diabetes. We hypothesized lifestyle intervention to be superior to standard care in decreasing levels of oxidative stress. The study was based on the single-centre, assessor-blinded, randomised, controlled U-turn trial (ClinicalTrial.gov NCT02417012). Persons with type 2 diabetes ˂ 10 years, ˂ 3 glucose lowering medications, no use of insulin, BMI 25-40 kgm A total of 77 participants, 21 participants receiving standard care and 56 participants receiving the lifestyle intervention, were included in the analysis. Mean age at baseline was 54.1 years (SD 9.1), 41% were women and mean duration of type 2 diabetes was 5.0 years (SD 2.8). From baseline to follow-up the lifestyle group experienced a 7% decrease in 8-oxoGuo (-0.15 nmolmmol creatinine 95% CI -0.27, -0.03), whereas standard care conversely was associated with a 8.5% increase in 8-oxoGuo (0.19 nmolmmol creatinine 95% CI 0.00, 0.40). The between group difference in 8-oxoGuo was -0.35 nmolmmol creatinine 95% CI -0.58, -0.12,, p 0.003. No between group difference was observed in 8-oxodG. A 12 months intensive exercise-based lifestyle intervention was associated with a decrease in RNA, but not DNA, oxidation in persons with type 2 diabetes.

Rosiglitazone protects INS-1E cells from human islet amyloid polypeptide toxicity.

Human islet amyloid polypeptide (hIAPP or amylin) is a hormone co-secreted with insulin by pancreatic β-cells, and is the main component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes and may be involved in β-cell dysfunction and death, observed in this disease. Thus, counteracting islet amyloid toxicity represents a therapeutic approach to preserve β-cell mass and function. In this sense, thiazolidinediones (TZDs), as rosiglitazone, have shown protective effects against other harmful insults to β-cells. For this reason, we investigated whether rosiglitazone could protect β-cells from hIAPP-induced cell death and the underlying mechanisms mediating such effect. Here, we show that rosiglitazone improved the viability of hIAPP-exposed INS-1E cells. This benefit is not dependent on the insulin-degrading enzyme (IDE) since rosiglitazone did not modulate IDE protein content and activity. However, rosiglitazone inhibited hIAPP fibrillation and decreased hIAPP-induced expression of CEBP homologous protein (CHOP) (CTL 100.0 ± 8.4 hIAPP 182.7 ± 19.1 hIAPP RGZ 102.8 ± 9.5), activating transcription factor-4 (ATF4) (CTL 100.0 ± 3.1 hIAPP 234.9 ± 19.3 hIAPP RGZ 129.6 ± 3.0) and phospho-eukaryotic initiation factor 2-alpha (p-eIF2α) (CTL 100.0 ± 31.1 hIAPP 234.1 ± 36.2 hIAPP RGZ 150.4 ± 18.0). These findings suggest that TZDs treatment may be a promising approach to preserve β-cell mass and function by inhibiting islet amyloid formation and decreasing endoplasmic reticulum stress hIAPP-induced.

Reducing the intestinal side effects of acarbose by baicalein through the regulation of gut microbiota An in vitro study.

Combination of dietary flavonoid-baicalein and acarbose reduces the risk that prediabetes will develop into type 2 diabetes mellitus however, the mechanism underlying this effect has not been clarified. In this study, the in vitro culture conditions of intestinal microorganisms from prediabetic mice were optimized to increase over 30% similarity between in vitro cultured and fecal samples. Baicalein and acarbose alone and in combination, and their corresponding starch hydrolysate were assayed by the in vitro model. The results indicated that the combination of baicalein with acarbose decreased gas production by reducing the residual starch ratio in starch hydrolysate and decreasing the dosage of acarbose, and that reducing the relative abundance of gut bacteria correlated with gas production is the main mechanism. This study provided a theoretical foundation for the development of flavonoid dietary supplements to enhance the efficacy of oral hypoglycemic agents with fewer side effects and higher efficacy.

Model for Integration of Monogenic Diabetes Diagnosis Into Routine Care The Personalized Diabetes Medicine Program.

To implement, disseminate, and evaluate a sustainable method for identifying, diagnosing, and promoting individualized therapy for monogenic diabetes. Patients were recruited into the implementation study through a screening questionnaire completed in the waiting room or through the patient portal, physician recognition, or self-referral. Patients suspected of having monogenic diabetes based on the processing of their questionnaire and other data through an algorithm underwent next-generation sequencing for 40 genes implicated in monogenic diabetes and related conditions. Three hundred thirteen probands with suspected monogenic diabetes (but most diagnosed with type 2 diabetes) were enrolled from October 2014 to January 2019. Sequencing identified 38 individuals with monogenic diabetes, with most variants found in GCK or HNF1A. Positivity rates for ascertainment methods were 3.1% for clinic screening, 5.3% for electronic health record portal screening, 16.5% for physician recognition, and 32.4% for self-referral. The algorithmic criterion of non-type 1 diabetes before age 30 years had an overall positivity rate of 15.0%. We successfully modeled the efficient incorporation of monogenic diabetes diagnosis into the diabetes care setting, using multiple strategies to screen and identify a subpopulation with a 12.1% prevalence of monogenic diabetes by molecular testing. Self-referral was particularly efficient (32% prevalence), suggesting that educating the lay public in addition to clinicians may be the most effective way to increase the diagnosis rate in monogenic diabetes. Scaling up this model will assure access to diagnosis and customized treatment among those with monogenic diabetes and, more broadly, access to personalized medicine across disease areas.

Long-Term Follow-Up on Morbidity Among Women With a History of Gestational Diabetes Mellitus A Systematic Review.

Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases. The aim was to review the literature for evidence of associations with morbidity other than T2DM and cardiovascular disease and with long-term mortality. A systematic review based on searches in Medline, Embase, and Cochrane Library until March 31, 2021, using a broad range of keywords. We extracted study characteristics and results on associations between GDM and disease occurrence at least 10 years postpartum, excluding studies on women with diabetes prior to pregnancy or only diabetes prior to outcome. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Newcastle-Ottawa Scale was used to assess risk of bias. We screened 3084 titles, 81 articles were assessed full-text, and 15 included in the review. The strongest evidence for an association was for kidney diseases, particularly in Black women. We found indication of an association with liver disease, possibly restricted to women with T2DM postpartum. The association between GDM and breast cancer had been studied extensively, but in most cases based on self-reported diagnosis and with conflicting results. Only sparse and inconsistent results were found for other cancers. No study on thyroid diseases was found, and no study reported on short-term or long-term mortality in women with a history of GDM. Given the frequency of GDM, there is a need for better evidence on possible long-term health consequences, in particular, studies based on comprehensive records of diagnosis of GDM and long-term health outcomes.

Effect of different antidiabetic medications on atherosclerotic cardiovascular disease (ASCVD) risk score among patients with type-2 diabetes mellitus A multicenter non-interventional observational study.

The aim of this study was to compare the clinical outcomes associated with different combinations of oral diabetic drugs among patients with type 2 diabetes mellitus. A prospective multicenter longitudinal, noninterventional observation study design was applied. At baseline (0 month), clinical parameters including glucose profile, renal function, lipid profile and risk assessment for cardiovascular risks were calculated. Mean Weighted difference (MWD) with heterogeneity and effect z was calculated to determine the risk reduction at the end of the study. A total of 1,657 were enrolled to different cohorts with response rate of 75.5%. The distribution of patients was based on prescribed drug. A total of 513 (30.9%) in G1 (metformin alone), 217 (13.09%) in G2 (metformin with Glimepiride), 231 (12.85%) in G3 (Metformin with Gliclazide), 384 (23.17%) in G4 (metformin with Sitagliptin) and 312 (18.89%) in G5 (Metformin with Saxagliptin). There was no significant different in all clinical and social variables at baseline. The Intergroup analysis showed significant differences with all the primary outcome variables except BMI (p 0.217) and eGFR (p 0.782) among patients using sulphonylurea (SU) combination (G2 G3). Findings also showed significant high frequency of emergency visit and hospitalization in G1 (78.16% 30.8%) as compared to SU (70.1% 28.3%, p 0.001) and DPP-4 (56.6% 20.4%, p 0.001). The overall reported effect was z 2.58, p 0.001 for ASCVD risk reduction assessment. The study concluded that significant effect of Dipeptidyl peptidase-4 inhibitor on reduction of hospitalization, lipid profile and also ASCVD risk score of type-II diabetes mellitus patients regardless of clinical comorbidities. Also, sulfonylurea combinations have showed significant reduction in LDL and triglycerides values.

Accuracy of Three Commercial Home-Use Hemoglobin A1c Tests.

Real-World Evidence Supporting Tandem Control-IQ Hybrid Closed-Loop Success in the Medicare and Medicaid Type 1 and Type 2 Diabetes Populations.

Single Anastomosis Jejuno-ileal (SAJI) a New Model of Malabsorptive Revisional Procedure for Insufficient Weight Loss or Weight Regain After Roux-en-Y Gastric Bypass.

In case of insufficient weight loss or weight regain or relapse of weight-related comorbidities after Roux-en-Y gastric bypass (RYGB), other procedures such as reduction of a large gastric pouch and stoma, lengthening of the Roux limb, conversion to sleeve gastrectomy andor bilio-pancreatic diversion with duodenal switch have been advocated. Single anastomosis jejuno-ileal (SAJI) is a new revisional simple operation performed after RYGB failure which adds malabsorption to the previous gastric bypass. SAJI includes a single jejuno-ileal anastomosis specifically joining the ileum 250-300 cm proximal to the ileo-caecal valve and the jejunum 30 cm below the gastro-jejunal anastomosis on the Roux limb of the previous RYGB. Thirty-one patients underwent SAJI for insufficient weight loss andor weight regain after RYGB. The percent total weight loss (%TWL) after RYGB and before SAJI was 21.8 ± 7.8. All SAJI operations were performed laparoscopically. The SAJI mean operating time was 145 min. Regarding weight loss after SAJI, %TWL is 27.2 ± 7.4, 31.2 ± 6.4, 33.7 ± 5.9 and 32.9 ± 5.2 at 12, 24, 36 and 48 months, respectively. Our series recorded a low rate of peri-operative and medium-term complications with a low grade of severity (Clavien-Dindo classification grade). One patient required reoperation 36 days after SAJI for epigastrium incarcerated incisional hernia at the previous RYGB laparotomy site. Mortality was 0. Comorbidity reductionresolution after SAJI is 83.2% for type 2 diabetes mellitus, 42.8% for arterial hypertension, 72.8% for dyslipidemia and 45.3% for OSA. Treatment of failed RYGB is challenging. SAJI is a less complicated, purely low invasive malabsorptive operation that should reach satisfactory %TWL and comorbidity reductionresolution.

Ethnic disparities attributed to the manifestation in and response to type 2 diabetes insights from metabolomics.

Type 2 diabetes (T2D) associated health disparities among different ethnicities have long been known. Ethnic variations also exist in T2D related comorbidities including insulin resistance, vascular complications and drug response. Genetic heterogeneity, dietary patterns, nutrient metabolism and gut microbiome composition attribute to ethnic disparities in both manifestation and progression of T2D. These factors differentially regulate the rate of metabolism and metabolic health. Metabolomics studies have indicated significant differences in carbohydrate, lipid and amino acid metabolism among ethnicities. Interestingly, genetic variations regulating lipid and amino acid metabolism might also contribute to inter-ethnic differences in T2D. Comprehensive and comparative metabolomics analysis between ethnicities might help to design personalized dietary regimen and newer therapeutic strategies. In the present review, we explore population based metabolomics data to identify inter-ethnic differences in metabolites and discuss how (a) genetic variations, (b) dietary patterns and (c) microbiome composition may attribute for such differences in T2D.

Clinical variable-based cluster analysis identifies novel subgroups with a distinct genetic signature, lipidomic pattern and cardio-renal risks in Asian patients with recent-onset type 2 diabetes.

We sought to subtype South East Asian patients with type 2 diabetes by de novo cluster analysis on clinical variables, and to determine whether the novel subgroups carry distinct genetic and lipidomic features as well as differential cardio-renal risks. Analysis by k-means algorithm was performed in 687 participants with recent-onset diabetes in Singapore. Genetic risk for beta cell dysfunction was assessed by polygenic risk score. We used a discovery-validation approach for the lipidomics study. Risks for cardio-renal complications were studied by survival analysis. Cluster analysis identified three novel diabetic subgroups, i.e. mild obesity-related diabetes (MOD, 45%), mild age-related diabetes with insulin insufficiency (MARD-II, 36%) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII, 19%). Compared with the MOD subgroup, MARD-II had a higher polygenic risk score for beta cell dysfunction. The SIRD-RII subgroup had higher levels of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (phosphatidylethanolamine and phosphatidylcholine), whereas the MARD-II subgroup had lower levels of sphingolipids and glycerophospholipids but higher levels of lysophosphatidylcholines. Over a median of 7.3 years follow-up, the SIRD-RII subgroup had the highest risks for incident heart failure and progressive kidney disease, while the MARD-II subgroup had moderately elevated risk for kidney disease progression. Cluster analysis on clinical variables identified novel subgroups with distinct genetic, lipidomic signatures and varying cardio-renal risks in South East Asian participants with type 2 diabetes. Our study suggests that this easily actionable approach may be adapted in other ethnic populations to stratify the heterogeneous type 2 diabetes population for precision medicine.

Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of kidney failure and has a substantial genetic component. Our aim was to identify novel genetic factors and genes contributing to DKD by performing meta-analysis of previous genome-wide association studies (GWAS) on DKD and by integrating the results with renal transcriptomics datasets. We performed GWAS meta-analyses using ten phenotypic definitions of DKD, including nearly 27,000 individuals with diabetes. Meta-analysis results were integrated with estimated quantitative trait locus data from human glomerular (N119) and tubular (N121) samples to perform transcriptome-wide association study. We also performed gene aggregate tests to jointly test all available common genetic markers within a gene, and combined the results with various kidney omics datasets. The meta-analysis identified a novel intronic variant (rs72831309) in the TENM2 gene associated with a lower risk of the combined chronic kidney disease (eGFR<60 mlmin per 1.73 m Altogether, the results point to novel genes contributing to the pathogenesis of DKD. The GWAS meta-analysis results can be accessed via the type 1 and type 2 diabetes (T1D and T2D, respectively) and Common Metabolic Diseases (CMD) Knowledge Portals, and downloaded on their respective download pages ( httpst1d.hugeamp.orgdownloads.html httpst2d.hugeamp.orgdownloads.html httpshugeamp.orgdownloads.html ).

Diagnosis and management of type 2 diabetes in children.

The incidence of type 2 diabetes in children has risen 4.8% over the past decade, correlating with steadily rising obesity rates in children. Updated guidelines from the American Academy of Pediatrics and the American Diabetes Association encourage early identification and pharmacologic intervention for children with type 2 diabetes. Because of the aggressive disease course in children, comprehensive treatment must include prevention of complications such as diabetic nephropathy and neuropathy as well as management of comorbidities such as cardiovascular disease and dyslipidemia. Because the highest incidence of type 2 diabetes is reported in patients from racial or ethnic minority groups and those of low socioeconomic status, clinicians must work with patients and families to identify socioeconomic disparities that could affect adherence to diabetes management plans and to connect patients with community resources.

Multivalent γ-PGA-Exendin-4 Conjugates to Target Pancreatic β-Cells.

Targeting of glucagon-like peptide 1 receptor (GLP-1R), expressed on the surface of pancreatic β-cells, is of great interest for the development of advanced therapies for diabetes and diagnostics for insulinoma. We report the conjugation of exendin-4 (Ex-4), an approved drug to treat type 2 diabetes, to poly-γ-glutamic acid (γ-PGA) to obtain more stable and effective GLP-1R ligands. Exendin-4 modified at Lysine-27 with PEG4-maleimide was conjugated to γ-PGA functionalized with furan, in different molar ratios, exploiting a chemoselective Diels-Alder cycloaddition. The γ-PGA presenting the highest number of conjugated Ex-4 molecules (average 120 per polymeric chain) showed a double affinity towards GLP-1R with respect to exendin per se, paving the way to improved therapeutic and diagnostic applications.

Cross-Talk between Obesity and Diabetes Introducing Polyphenols as an Effective Phytomedicine to Combat the Dual Sword Diabesity.

Obesity-associated diabetes mellitus, a chronic metabolic affliction accounting for 90% of all diabetic patients, has been affecting humanity extremely badly and escalating the risk of developing other serious disorders. It is observed that 0.4 billion people globally have diabetes, whose major cause is obesity. Currently, innumerable synthetic drugs like alogliptin and rosiglitazone are being used to get through diabetes, but they have certain complications, restrictions with severe side effects, and toxicity issues. Recently, the frequency of plant-derived phytochemicals as advantageous substitutes against diabesity is increasing progressively due to their unparalleled benefit of producing less side effects and toxicity. Of these phytochemicals, dietary polyphenols have been accepted as potent agents against the dual sword diabesity. These polyphenols target certain genes and molecular pathways through dual mechanisms such as adiponectin upregulation, cannabinoid receptor antagonism, free fatty acid oxidation, ghrelin antagonism, glucocorticoid inhibition, sodium-glucose cotransporter inhibition, oxidative stress and inflammation inhibition etc. which sequentially help to combat both diabetes and obesity. In this review, we have summarized the most beneficial natural polyphenols along with their complex molecular pathways during diabesity.

Improved glycaemic control and weight benefit with iGlarLixi versus insulin glargine 100 UmL in Chinese people with type 2 diabetes advancing their therapy from basal insulin plus oral antihyperglycaemic drugs Results from the LixiLan-L-CN randomized controlled trial.

To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 11 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. In total, 426 participants were randomized to iGlarLixi (n 212) or iGlar (n 214). Mean age was 58 years, 67% had a body mass index ≥24 kgm iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.

Finerenone a mineralocorticoid receptor antagonist for the treatment of chronic kidney disease associated with type 2 diabetes.

Approximately 40% of people with type 2 diabetes (T2D) also have chronic kidney disease (CKD), which substantially increases their risk of cardiovascular (CV)-related complications and mortality. Until recently, no approved therapies have directly targeted inflammatory and fibrotic pathways that drive disease progression and organ damage in patients with CKD associated with T2D. Finerenone is a potent, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that targets fibrosis and inflammation by blocking overactivation of the MR in the kidneys and heart. Finerenone has been associated with significant reductions in kidney- and CV-related endpoints compared with placebo and minimal effects on serum potassium and kidney function in phase III trials involving >13,000 patients with diabetic kidney disease (DKD). In addition to reviewing the clinical data, this review compares the properties of finerenone with those of the older steroidal MRAs spironolactone and eplerenone. Unlike spironolactone and eplerenone, finerenone has demonstrated a favorable benefit-risk profile offering an effective new treatment for patients with CKD associated with T2D. Increases in serum potassium are predictable and manageable and should not discourage the use of finerenone in clinical practice. It is important to discuss where finerenone fits best within the current DKD management landscape.

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications.

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Williss polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

DUAL I China Improved glycemic control with IDegLira versus its individual components in a randomized trial with Chinese participants with type 2 diabetes uncontrolled on oral antidiabetic drugs.

DUAL I China, one of the DUAL trials, assessed efficacysafety of insulin degludecliraglutide (IDegLira) in Chinese adults with type 2 diabetes (T2D) not controlled by oral antidiabetic drugs (OADs). This phase 3a, treat-to-target multicenter trial randomized participants (glycated hemoglobin HbA1c 53.0-85.8 mmolmol previous metformin ± another OAD) 211 to IDegLira (n 361), degludec (n 179), or liraglutide (n 180). Primary endpoint was change in HbA1c after 26 weeks. Secondary endpoints included HbA1c < 53.0 mmolmol attainment, weight change, treatment-emergent hypoglycemia, end-of-treatment insulin dose, and safety. At 26 weeks, HbA1c had decreased by a mean 18.12 mmoLmoL (IDegLira), 12.37 mmoLmoL (degludec) (estimated treatment difference ETD -6.50 mmoLmoL 95% confidence interval CI -7.96, -5.04 P < .0001), and 11.33 mmoLmoL (liraglutide) (ETD -6.87 mmoLmoL 95% CI -8.33, -5.41 P < 0.0001), indicating noninferiority for IDegLira vs degludec and superiority vs liraglutide. HbA1c < 53.0 mmoLmoL attainment was 77.0% (IDegLira), 46.4% (degludec), and 48.3% (liraglutide). Mean weight change with IDegLira (0.1 kg) was superior to degludec (1.2 kg) (ETD -1.08 kg 96% CI -1.55, -0.62 P < 0.0001). Severe or confirmed hypoglycemic event rates were 0.24 (IDegLira) and 0.17 (degludec) episodesparticipant-year (estimated rate ratio 1.46 95% CI 0.71, 3.02 P .3008, not significant). At the end of treatment, the IDegLira insulin dose was lower (24.5 Ud) vs degludec (30.3 Ud) (ETD -5.49 U 95% CI -7.77, -3.21 P < 0.0001). No unexpected safety issues occurred. IDegLira is efficacious and well tolerated in Chinese adults with T2D not controlled by OADs. 背景 作为DUAL试验之一的DUAL I China评估了未口服抗糖药物(OADs)控制血糖的中国成人2型糖尿病(T2D)患者应用德谷胰岛素利拉鲁肽(IDegLira)的有效性安全性。 方法 这项3a期, 治疗导向的多中心随机对照试验中, 受试者糖化血红蛋白(HbA1c)为53.0-85.8 mmolmol, 之前治疗为二甲双胍配合或不配合其他口服抗糖药物。按211的比例分别给予IDegLira(n361), 德谷胰岛素(n179)或利拉鲁肽(n180)。主要终点是26周后HbA1c的变化。次要终点包括HbA1c<53.0 mmolmol, 体重变化, 治疗后出现的低血糖, 治疗结束时的胰岛素剂量, 以及安全性。 结果 治疗26周时, 糖化血红蛋白平均下降18.12mmolmol(IDegLira), 12.37mmolmol(德谷胰岛素)(治疗前后差值估计(ETD)为-6.50 mmoLm ol, 95%可信区间−7.96, −5.04, P<0.0001)和11.33 mmoLmol(利拉鲁肽)(ETD−6.87 mmoLmol, 95%置信区间−8.33, −5.41, P<0.0001), 表明IDegLira相对于德谷胰岛素的非劣效性, 以及相对于利拉鲁肽的优越性。糖化血红蛋白(HbA1c)的达标率为77.0%(IDegLira), 46.4%(德谷胰岛素)和48.3%(利拉鲁肽)。平均体重变化IDegLira组(0.1 kg)优于德谷胰岛素组(1.2 kg), ETD为-1.08 kg(95%CI−1.5 5, −0.62), P<0.001。严重或确认的低血糖事件发生率分别为0.24(IDegLira)和0.17(德谷胰岛素)次参与者-年, 估计比率为1.46(95%CI0.71, 3.02), P.3008, 无显著意义。治疗结束时, IDegLira胰岛素剂量(24.5U天)低于德谷胰岛素(30.3U天), ETD为-5.49U95%CI−7.77, −3.21, P<0.0001。没有发生意外安全事件。 结论 IDegLira治疗非OADs控制的中国成人T2D是有效的且耐受性良好。.

Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes.

Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated. Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes. Of the 5988 patients enrolled, 2938 (49%) had diabetes. The risk of the primary outcome (first hospitalization for heart failure or cardiovascular death), total hospitalizations for heart failure, and estimated glomerular filtration rate decline was higher in patients with diabetes. Empagliflozin reduced the rate of the primary outcome irrespective of diabetes status (hazard ratio, 0.79 95% CI, 0.67, 0.94 for patients with diabetes versus hazard ratio, 0.78 95% CI, 0.64, 0.95 in patients without diabetes In patients with heart failure and a preserved ejection fraction enrolled in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), empagliflozin significantly reduced the risk of heart failure outcomes irrespective of diabetes status at baseline. URL httpswww. gov Unique identifier NCT03057951.

Assessment of quality of care provided to adults with type 2 diabetes mellitus at public hospitals in Gamo Gofa zone, Southern Ethiopia Facility based Cross-Sectional study.

Proactive management of type 2 diabetes is important for restoring beta-cell function and improving sustained blood glucose control. Evidence on quality of diabetes care in Ethiopia is inadequate. Facility-based cross-sectional study was conducted to assess level of quality of care provided to adult type 2 diabetes patients at three public hospitals in Gamo Gofa Zone, Southern Ethiopia. A total of 210 adult type 2 diabetes patients were included. The mean age of patients was 44.1 ± 9.94 years. Fifty-one (24.3%) of patients adhered to prescribed medicines. Sixty-seven (31.9%) patients could benefit from neuropathy screening and referral. Diabetes-specific evidence-based guidelines, operational plan to reduce overweight and obesity were not available. There was no periodic lipid profile, renal function and glycated haemoglobin testing. Sixty-three (30%) patients achieved fasting blood glucose (FBG) level. Only 41 (19.5%) achieved the recommended target value for composite intermediate outcomes. All three sub-components of quality care structure, process and outcome (SPO) were below the agreed minimum score and the quality of care provided to adult type 2 diabetes was poor. Only 41 (19.5%) achieved agreed quality indicator targets for type 2 diabetes (fasting blood glucose blood pressure and low-density lipoprotein cholesterol). The quality of care provided to adult type 2 diabetes patients was poor particularly in areas such as availability of evidence-based guidelines, operational plan to reduce obesity, monitoring of lipid profile and glycaemic control. Therefore, developing strategies for addressing structure, process and outcome-related gaps by involving all stakeholders is critical for improving the quality of care provided to these patients.

Childrens food choices are highly dependent on patterns of parenting practices and food availability at home in families at high risk for type 2 diabetes in Europe Cross-sectional results from the Feel4Diabetes study.

Food parenting practices, behaviours and food availability at home are associated with childrens food choices however, these associations have been mainly studied for each parenting practice separately and focused mostly on healthy populations. The aim of the study was to identify patterns of parenting practices (including data regarding food availability at home, food and physical activity-related behaviours and rewards) and to investigate their cross-sectional associations with childrens food choices in families at high risk for type 2 diabetes (T2D). Data of parents and children (n 2278), from the Feel4Diabetes study conducted in six European countries, were collected using validated questionnaires. The data analysed included childrens food choices, food availability at home and food and physical activity-related parenting practices. Four patterns of parenting practices were identified using principal component analysis, and associations between those components and childrens food choices were assessed using adjusted, individual linear regressions. Parenting patterns focusing on unhealthy habits, such as allowing unhealthy snacks and unlimited screen time, providing higher availability of unhealthy foods at home, rewarding with snacks and screen time, were positively associated with childrens unhealthy food choices (consumption of savourysweet snacks, fizzy drinks, etc.). The parenting patterns providing fruitvegetables at home, consuming fruit, and being physically active with the child were positively associated with childrens healthier food choices (consumption of fruit, vegetables, whole grain cereals, etc.). Public health initiatives should focus on high-risk families for T2D, assisting them to adopt appropriate parenting practices and behaviours to promote healthier food choices for children.

Serum Cortisol, 25 (OH)D, and Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus.

The effects of cortisol on cardiovascular diseases (CVD) and CVD risk are unknown, especially in patients with type 2 diabetes mellitus (T2DM). Furthermore, it is unclear whether 25 (OH)D can alter the associations of cortisol with CVD and CVD risk factors. Thus, the present study was to investigate the associations of serum cortisol with CVD and CVD risk factors and whether 25 (OH)D altered these associations among patients with T2DM. A 1 SD increase in cortisol was associated with a higher prevalence of stroke (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.05, 1.50). Elevated cortisol was associated with related cardiovascular risk factors, including deceased Serum cortisol was associated with the prevalence of stroke and cardiovascular risk factors, and the associations of cortisol with cardiovascular risk factors were moderated by 25 (OH)D, suggesting that T2DM patients with exposure to lower 25 (OH)D levels and higher cortisol levels were more susceptible to have higher cardiovascular risk factors.

Acute Pancreatitis in Individuals with COVID-19 A Case Report and Critical Review of Literature.

Involvement of gastrointestinal tract has been reported in individuals diagnosed with COVID-19. Herein, we report a case of 65-year-old woman with type 2 diabetes mellitus, hypertension, and end-stage renal disease undergoing hemodialysis who was initially diagnosed with COVID-19 on a screening test. During the course of the disease, her respiratory symptoms remained mild however, she developed acute pancreatitis leading to severe hypertension and hyperosmolar hyperglycemic state. During the hospitalization and treatment of acute pancreatitis, hyperglycemia, and hypertension, her condition improved and she was discharged in stable condition.

Risk Factors for Nonalcoholic Fatty Liver Disease in Postmenopausal Women with Type 2 Diabetes Mellitus and the Correlation with Bone Mineral Density at Different Locations.

To explore the risk factors for nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with type 2 diabetes mellitus (T2DM) and the correlation with bone mineral density (BMD) in different areas of the body. A total of 434 postmenopausal women with T2DM were enrolled and categorized as 198 patients in the NAFLD group and 236 patients in the non-NAFLD group based on color Doppler ultrasound of the liver. The BMD of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. In postmenopausal women with T2DM, the prevalence of NAFLD was 45.6%. The body mass index (BMI), systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), triacylglycerol (TG), uric acid (UA), and homeostatic model assessment for insulin resistance (HOMA-IR) C-peptide (CP) were significantly higher in the NAFLD group than in the non-NFALD group, and the duration of diabetes, and high-density lipoprotein cholesterol (HDL-C) were lower than in the non-NAFLD group (P < 0.05). Logistic regression analysis revealed that BMI (odds ratio OR 1.303, 95% confidence interval CI 1.152-1.346), HbA1c (OR 1.263, 95% CI 1.095-1.392), TG (OR 1.263, 95% CI 1.031-1.601), and SUA (OR 1.005, 95% CI 1.001-1.007) were correlated with NAFLD (P < 0.05). The BMD of the total hip and femoral neck in the NAFLD group was higher than in the non-NAFLD group (P < 0.05). Complicated NAFLD in postmenopausal women with T2DM is associated with weight gain, poor blood glucose control, abnormal lipid metabolism, and elevated UA levels. In addition, the NAFLD group had higher femoral neck and total hip BMD than the non-NAFLD group, suggesting NAFLD in postmenopausal women with T2DM may reduce the risk of osteoporosis.

Salvianolic acid A promotes mitochondrial biogenesis and function via regulating the AMPKPGC-1α signaling pathway in HUVECs.

Mitochondrial dysregulation is an important pathology that leads to endothelial dysfunction, and the occurrence and development of cardiovascular diseases. Salvianolic acid A (SAA) has been demonstrated to be effective in the treatment of vascular complications of type 2 diabetes mellitus. Limited information has been reported on the effects of SAA on mitochondrial function in endothelial cells. In the present study, the effects of SAA on mitochondrial biogenesis and the related underlying mechanisms were investigated in human umbilical vein endothelial cells (HUVECs). Mitotracker red staining and transmission electron microscopy were used to evaluate the effect of SAA on mitochondrial quality. The effect of SAA treatment on mitochondrial DNAnuclear DNA ratio of HUVECs was detected by real-time quantitative PCR. Western blot was used to determine the protein expression levels of complex III and Complex IV of mitochondrial oxidative phosphorylation subunit, and ATP production was determined by ATP test kit. Real-time quantitative PCR and Western blot were used to determine the effects of SAA on the expression of peroxisome proliferator-activated receptor γ coactivator (PGC-1α) and its target genes nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) proteins and genes. Finally, in the presence of 5AMP-activated protein kinase (AMPK) specific inhibitors, the expression of PGC-1α, NRF1 and TFAM proteins and the phosphorylation levels of AMPK and Acetyl CoA Carboxylase (ACC) were detected by Western blot or real-time quantitative PCR. The results showed that SAA treatment significantly promoted mitochondrial biogenesis and enhanced mitochondrial function of HUVECs. SAA significantly increased the expression levels of PGC-1α and its target genes NRF1 and (TFAM), a key regulator of mitochondrial biogenesis in HUVECs. These enhancements were accompanied by significantly increased phosphorylation of AMPK and ACC, and were significantly inhibited by specific AMPK inhibitors. These results suggest that SAA may promote mitochondrial biogenesis in endothelial cells by activating the AMPK-mediated PGC-1αTFAM signaling pathway. These data provide new insights into the mechanism of action of SAA in treating diabetic vascular complications.

Whey protein and xylitol complex alleviate type 2 diabetes in C57BL6 mice by regulating the intestinal microbiota.

Type 2 diabetes (T2D) is a metabolic disorder that has become a major threat to public health. Epidemiological and experimental studies have suggested that whey protein isolate (WPI) and xylitol (XY) play an important role on T2D. This manuscript hypothesizes the supplementation of whey protein and xylitol complex (WXY) has the hypoglycemic and hyperlipidemia effect of T2D mice induced by the conjoint action of a high-fat diet and streptozotocin (STZ) by modulating of intestinal microbiota. The mice with diabetes displayed higher levels of fasting blood glucose (FBG), insulin, glycosylated hemoglobin, total triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase and other serum parameters than the normal mice. Treatment with WXY for 6 weeks significantly modulated the levels of FBG and insulin, improved insulin sensitivity, pancreas impairment and liver function in T2D mice, and the effect was better than that observed with WPI and XY groups. Moreover, supplementation with WXY significantly changed the diversity and composition of the intestinal microbiota in T2D mice and restored the intestinal bacteria associated with T2D (Firmicutes, Bacteroidetes, and Lactobacillus). This may be a potential mechanism for alleviating T2D symptoms. Spearman correlation analysis showed that the relative abundances of specific genera (Turicibacter, LachnospiraceaeNK4A136group, Lactobacillus, CandidatusSaccharimonas, Faecalibaculum and CoriobacteriaceaeUCG-002) were correlated with the levels of blood glucose and serum parameters. Therefore, WXY may be considered a promising dietary supplement for T2D treatment in the future.

Dietary fiber of Tartary buckwheat bran modified by steam explosion alleviates hyperglycemia and modulates gut microbiota in dbdb mice.

Type 2 diabetes is a serious threat to human health. Tartary buckwheat bran dietary fiber has good hypoglycemic activity, with its modification widely studied. However, the hypoglycemic activity of steam explosion modified Tartary buckwheat bran soluble dietary fiber (SE-SDF) has not been reported. This research aimed at investigating the hypoglycemic effect with its underlying mechanism of SE-SDF on type 2 diabetic dbdb mice. Results found SE-SDF decreased the levels of fasting blood glucose and glycosylated hemoglobin while improved oral glucose tolerance, insulin resistance, and injuries of liver, pancreas, and colon in diabetic dbdb mice. Additionally, SE-SDF up-regulated the protein expression levels of hepatic phosphatidylinositol 3 kinase (PI3K), G protein-coupled receptor43 (GPR43), and phospho-adenosine monophosphate activated protein kinase (p-AMPK), whereas inhibited the protein expression levels of hepatic fork-head transcription factor O1 (FoxO1), phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Moreover, SE-SDF increased the production of fecal short chain fatty acids (SCFAs) and the expression of colon GPR43 and the concentration of serum glucagon like peptide-1 (GLP-1), leading to reduced ratio of FirmicutesBacteroidetes but increased relative abundance of Parabacteroides, norankfMuribaculaceae, Alloprevotella, Ruminiclostridium9, unclassifiedfRuminococcaceae, and LachnospiraceaeNK4A136group. These findings suggested that SE-SDF ameliorated type 2 diabetes via activating the liver PI3KAktFoxO1 and GPR43AMPK signaling pathways and modulating the gut microbiota-SCFAs-GPR43GLP-1 signaling axis.

The bioactivity of prenylated stilbenoids and their structure-activity relationship.

Dietary prenylated stilbenoids present in many food resources, and have good bioactivities. However, their structure-activity relationships are rarely reported. In this work, eighteen C- and O-prenylated stilbenoids were chemically semisynthesized using one-step approach. They all could inhibit sugar digestive enzymes, including α-glucosidase and α-amylase. 4-Geranyl piceatannol from jackfruit showed the strongest activity by suppressing dipeptidyl peptidase-IV (DPP-IV) activity. The enzyme inhibition kinetics were measured and the inhibition mechanism was revealed. Evaluation of antioxidant activity highlighted that the introduction of prenyl with increasing prenyl chain length can significantly increase the antioxidant activity of stilbenoids. Our results suggested that prenylated stilbenoids could be used as functional food additives to decrease postprandial blood sugar levels by inhibiting sugar digestive enzymes and DPP-IV. Prenylated stilbenoids present remarkable DPP-IV inhibitory activity, providing more useful information for the prevention of type 2 diabetes.

Anti-diabetic and anti-obesity Efficacy evaluation and exploitation of polyphenols in fruits and vegetables.

Polyphenols are a group of secondary plant metabolites widely present in diets and have antagonistic effects on some chronic metabolic diseases, like type 2 diabetes (T2D) and obesity. We attempt to investigate the effects of polyphenols in fruits and vegetables on reducing the risk of T2D and obesity by collecting epidemiological evidence, including cross-sectional survey (CSS), prospective cohort study (PCS), and randomized controlled trial (RCT). Further, we provide possible mechanisms for the anti-diabetic effects including protecting pancreatic β-cells, affecting glucose digestion, absorption, and uptake, and activating glucoselipid metabolism pathways, while improving obesity by reducing lipid accumulation, regulating intestinal microflora, alleviating inflammation, and reducing food intake. Polyphenols also play an important role in the relationship between T2D and obesity. On the one hand, obesity is a low-grade chronic inflammation causing insulin resistance, so polyphenols can reduce T2D risk by improving obesity. On the other hand, obesity decreases the polyphenols bioavailability by disturbing gastrointestinal microflora, thus increasing T2D risk. These are instructive for diets and bring considerable development value. Therefore, we discussed the hotspots of polyphenols exploitation in the food industry, including masking bitter and astringent taste, ensuring stability, and improving the bioavailability, which provides ideas for polyphenols application in anti-diabetics and anti-obesity.

Barriers and Facilitators to Diabetes Self-Management in Pregnant Women with Pre-existing Type 2 Diabetes Mellitus A Scoping Review.

Background Pregnant women with pre-existing type 2 diabetes mellitus (T2DM) are at risk for poor maternal and neonatal health outcomes. Previous systematic reviews in pregnant women with T2DM have focused on physical activity, blood glucose monitoring, and insulin injections. Objective The purpose of this scoping review was to examine the barriers and facilitators to diabetes self-management in pregnant women with pre-existing type 2 diabetes mellitus. Method PubMed, CINAHL, and EMBASE databases were searched using the PRISMA-ScR guidelines. Inclusion criteria included manuscripts written in English and qualitative studies. Consensus statements were excluded. A metasummary was used to identify patterns in barriers and facilitators across studies. A vote-counting method was used to summarize qualitative findings. Results A total of ten qualitative publications was selected. This review suggests four themes describing barriers, included barriers of diabetes self-management in pregnancy, stress related to pregnancy with diabetes, a barrier to access to health care, and sensing a loss of control. The fifth theme described facilitators of diabetes self-management in pregnancy. Conclusion This supports an integrative model of maternity care and culturally relevant practices to overcome critical barriers and optimize key facilitators to enhance diabetes self-management behaviors and improve maternal and neonatal health outcomes.

Targeting ferroptosis with miR-144-3p to attenuate pancreatic β cells dysfunction via regulating USP22SIRT1 in type 2 diabetes.

Recently, ferroptosis has been implicated in the pathologic process of several diseases including type 2 diabetes mellitus (T2DM). However, molecular mechanisms underlying ferroptosis in T2DM remain obscure. Twenty four mice were included in this study. T2DM model mice were established by a high-fat diet combined with streptozotocin injection. INS-1 cells were stimulated with high glucose (HG). Cell viability was detected by CCK-8 kit. The levels of GSH, MDA, iron, and lipid ROS, and SOD activity, were detected by the corresponding kits. The interaction between miR-144-3p and USP22 was validated by dual-luciferase reporter assay. The relationship between USP22 and its substrate was verified using Co-IP and ubiquitination assays. The mRNA and protein expressions were examined by RT-qPCR and western blot, respectively. The functions of β cells in vitro and in vivo were evaluated glucose-stimulated insulin secretion test and HOMA-β, respectively. Ferroptosis occurred in the pancreas of T2DM mice and HG-induced INS-1 cells. Silencing miR-144-3p blocked the effect of HG on the cell viability and accumulation of lipid peroxides, thereby improving the insulin secretion in INS-1 cells. Mechanistically, USP22 is a direct target of miR-144-3p, which could stabilize SIRT1 expression, thereby suppressing ferroptosis. Overexpressing USP22 attenuated deleterious roles of HG in INS-1 cells but its roles were reversed by up-regulating miR-144-3p. In vivo study demonstrated that miR-144-3p antagomir exerted an anti-hyperglycemic effect and regulated the ferroptosis-related proteins in the pancreas. The up-regulation of miR-144-3p suppressed USP22SIRT1 to induce ferroptosis, which causes pancreatic β cells dysfunction, thereby promoting T2DM development.

Effect of race on cardiometabolic responses to once-weekly exenatide insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

To determine whether there were racial differences in short-term cardiometabolic responses to once-weekly exenatide (EQW) in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A Mean 6-month placebo-adjusted HbA Short-term cardiometabolic responses to EQW were similar in the main racial groups in EXSCEL, apart from a greater pulse rate increase in Asians. httpsclinicaltrials.gov NCT01144338.

Peripheral arterial disease progression and ankle brachial index a cohort study with newly diagnosed patients with type 2 diabetes.

Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM). Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis. We performed a 3-year prospective cohort study with two groups group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 221 newly diagnosed drug-naive (< 3 months) patients with T2DM. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms. As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p NS) and improved glycemic and lipid control during follow-up glycated hemoglobin (HbA1c) 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05 LDL 132 ± 45 vs 113 ± 38 mgdL, p < 0.01, respectively. When compared, patients who evolved with normalization or maintained normal ABI levels at the end Group A, N 60 (42%) with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) Group B, N 26 (18%), an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r - 0.3, p 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r - 0.3 p < 0.05). Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients.

Effect of performing high-intensity interval training and resistance training on the same day vs. different days in women with type 2 diabetes.

Type 2 diabetes (T2D) is associated with chronic inflammation as a critical factor for muscle atrophy and disease progression. Although the combination of aerobic and resistance training leads to more significant improvements in health-related indices for T2D patients, the interference effect in concurrent training can decrease positive adaptations. The purpose of this study was to investigate the physiological adaptations in performing high-intensity interval training (HIIT) and resistance training on the same day vs. different days in T2D patients. Twenty-four non-athletic 45-65-year-old women with T2D participated in an 8-week intervention. They were randomly divided into three groups same days (SD), different days (DD), and treatment as usual (control). SD group had resistance training followed by HIIT on Saturday, Monday, and Wednesday. In contrast, the DD group had the same volume of resistance training on Saturday, Monday, and Wednesday and HIIT on Sunday, Tuesday, and Thursday, with Friday as a resting day. Blood samples were collected 24 h before the first and 48 h after the last session in each group to measure glucose, insulin, glycosylated hemoglobin, IGF1, IL1β, CRP, lipid profile, miR-146a, and miR-29b. Three subjects dropped out during the study, and 21 participants (SD 7, DD 6, Control 8) completed the 8-week intervention. MiR-146a changed significantly (P 0.006) in both SD and DD groups compared to the control group. IGF1 (P 0.001) and fat-free mass (P 0.001) changed significantly in SD and DD groups compared to the control group, and also DD led to more significant increases in IGF1 and fat-free mass in comparison with SD. MiR-29 (P 0.001) changed significantly in the DD group compared to the control group. The reduction of IL-1β, fat mass and insulin resistance was significant in SD and DD compared to the control group DD showed more potent effects than the SD group on the fat mass (P 0.001) and insulin resistance (P 0.001). This study demonstrated that a combination of HIIT and resistance training could be practical for improving health-related outcomes in T2D. Our study indicated for the first time that training strength and HIIT on separate days appeared to be more effective to combat muscle atrophy and insulin resistance.

Near-infrared light reduces glia activation and modulates neuroinflammation in the brains of diet-induced obese mice.

Neuroinflammation is a key event in neurodegenerative conditions such as Alzheimers disease (AD) and characterizes metabolic pathologies like obesity and type 2 diabetes (T2D). Growing evidence in humans shows that obesity increases the risk of developing AD by threefold. Hippocampal neuroinflammation in rodents correlates with poor memory performance, suggesting that it contributes to cognitive decline. Here we propose that reducing obesityT2D-driven neuroinflammation may prevent the progression of cognitive decline associated with AD-like neurodegenerative states. Near-infrared light (NIR) has attracted increasing attention as it was shown to improve learning and memory in both humans and animal models. We previously reported that transcranial NIR delivery reduced amyloid beta and Tau pathology and improved memory function in mouse models of AD. Here, we report the effects of NIR in preventing obesity-induced neuroinflammation in a diet-induced obese mouse model. Five-week-old wild-type mice were fed a high-fat diet (HFD) for 13 weeks to induce obesity prior to transcranial delivery of NIR for 4 weeks during 90-s sessions given 5 days a week. After sacrifice, brain slices were subjected to free-floating immunofluorescence for microglia and astrocyte markers to evaluate glial activation and quantitative real-time polymerase chain reaction (PCR) to evaluate expression levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). The hippocampal and cortical regions of the HFD group had increased expression of the activated microglial marker CD68 and the astrocytic marker glial fibrillary acidic protein. NIR-treated HFD groups showed decreased levels of these markers. PCR revealed that hippocampal tissue from the HFD group had increased levels of pro-inflammatory interleukin (IL)-1β and tumor necrosis factor-α. Interestingly, the same samples showed increased levels of the anti-inflammatory IL-10. All these changes were attenuated by NIR treatment. Lastly, hippocampal levels of the neurotrophic factor BDNF were increased in NIR-treated HFD mice, compared to untreated HFD mice. The marked reductions in glial activation and pro-inflammatory cytokines along with elevated BDNF provide insights into how NIR could reduce neuroinflammation. These results support the use of NIR as a potential non-invasive and preventive therapeutic approach against chronic obesity-induced deficits that are known to occur with AD neuropathology.

Maternal risk factors associated with offspring biliary atresia population-based study.

Biliary atresia (BA) is a progressive, idiopathic, fibro-obliterative disease of the intra and extrahepatic biliary tree. If untreated, it results in severe liver injury and death. The etiology and pathogenesis of BA remain unclear. Few studies have investigated the association between maternal illnessdrug use and the occurrence of BA in offspring. We used the data from the Birth Certificate Application of Taiwan and linked to National Health Insurance Research Database and Taiwan Maternal and Child Health Database for the years 2004 to 2017 (N 1,647,231) on 202203, and identified BA cases according to diagnosis and procedure code. A total of 285 BA cases were identified. Mothers with type 2 diabetes mellitus and non-dependent drug abuse had higher rates having BA children than non-BA children, with an odds ratio of 2.17 (95% confidence interval CI 1.04-4.53) and OR 3.02 (95% CI 1.34-6.78), respectively. These results support the notion that BA occurrence is related to maternal reasons. Further studies should be designed to identify additional maternal and pregnancy risk factors and to understand the underlying pathophysiology. 1. The occurrence of offspring biliary atresia may be related to maternal illnessdrug use. 2. Maternal drug abuse and type 2 diabetes mellitus pose a high risk for offspring biliary atresia. 3. If maternal etiology is found, biliary atresia might be a preventable disease.

AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids.

Phospholipid levels are influenced by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamatergic transmission and cortical excitability. Whether changes in peripheral metabolism affect brain lipid levels and cortical excitability remains unknown. Here, we show that levels of lysophosphatidic acid (LPA) species in the blood and cerebrospinal fluid are elevated after overnight fasting and lead to higher cortical excitability. LPA-related cortical excitability increases fasting-induced hyperphagia, and is decreased following inhibition of LPA synthesis. Mice expressing a human mutation (Prg-1

Phenotypic decanalization driven by social determinants could explain variance patterns for glycemia in adult urban Argentinian population.

Type 2 diabetes, one of the major causes of death and disability worldwide, is characterized by problems in the homeostasis of blood glucose. Current preventive policies focus mainly on individual behaviors (diet, exercise, salt and alcohol consumption). Recent hypotheses state that the higher incidence of metabolic disease in some human populations may be related to phenotypic decanalization causing a heightened phenotypic variance in response to unusual or stressful environmental conditions, although the nature of these conditions is under debate. Our aim was to explore variability patterns of fasting blood glucose to test phenotypic decanalization as a possible explanation of heightened prevalence for type 2 diabetes in some groups and to detect variables associated with its variance using a nation-wide survey of Argentinian adult population. We found patterns of higher local variance for fasting glycemia associated with lower income and educational attainment. We detected no meaningful association of glycemia or its variability with covariates related to individual behaviors (diet, physical activity, salt or alcohol consumption). Our results were consistent with the decanalization hypothesis for fasting glycemia, which appears associated to socioeconomic disadvantage. We therefore propose changes in public policy and discuss the implications for data gathering and further analyses.

Vildagliptin-Derived Dipeptidyl Peptidase 9 (DPP9) Inhibitors Identification of a DPP89-Specific Lead.

Vildagliptin is a marketed DPP4 inhibitor, used in the management of type 2 diabetes. The molecule also has notable DPP89 affinity, with some preference for DPP9. Therefore, we aimed to use vildagliptin as a starting point for selective DPP89 inhibitors, and to engineer out the parent compounds DPP4-affinity. In addition, we wanted to identify substructures in the obtained molecules that allow their further optimization into inhibitors with maximal DPP9 selectivity. Various 2S-cyanopyrrolidines and isoindoline were investigated as P1 residues of vildagliptin analogs. The obtained set was expanded with derivatives bearing O-substituted, N-(3-hydroxyadamantyl)glycine moieties at the P2 position. In this way, representatives were discovered with DPP89 potencies comparable to the parent molecule, but with overall selectivity towards DPP4, DPP2, FAP, and PREP. Furthermore, the most promising molecules in this series have a 4- to 7-fold preference for DPP9 over DPP8. Finally, a molecular dynamics study was carried out to maximize our insight into experimental selectivity data.

Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC) a nested case-control study.

Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk . We performed a population-based nested case-control study of 28 137 PDAC cases and 261 219 matched-controls in England. We described the associations of biomarkers with risk of PDAC using fractional polynomials and 5-year time trends using joinpoint regression. Associations with comorbidities and medication use were evaluated using conditional logistic regression. Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while following a U-shaped relationship for BMI and haemoglobin. Five-year trends showed biphasic BMI decrease and HbA1c increase prior to PDAC early-gradual changes 2-3 years prior, followed by late-rapid changes 1-2 years prior. Liver markers and blood counts (white blood cell, platelets) showed monophasic rapid-increase approximately 1 year prior. Recent diagnosis of pancreatic cyst, pancreatitis, type 2 diabetes and initiation of certain glucose-lowering and acid-regulating therapies were associated with highest risk of PDAC. Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while followed a U-shaped relationship for BMI and haemoglobin. BMI and HbA1c derange biphasically approximately 3 years prior while liver markers and blood counts (white blood cell, platelets) derange monophasically approximately 1 year prior to PDAC. Profiling these in combination with their temporality could inform earlier PDAC diagnosis.

Effect of glucagon-like peptide 1 receptor agonists on the renal protection in patients with type 2 diabetes A systematic review and meta-analysis.

Glucagon-like peptide 1(GLP-1) receptor agonists are used in patients with type 2 diabetes as hypoglycemic drugs a growing body of evidence has clarified their renoprotective benefits. We performed a meta-analysis to summarize the most recent evidence on the renal benefits of GLP-1 receptor agonists from clinical trials of patients with type 2 diabetes. This meta-analysis used a fixed-effects model to estimate the risk ratio (RR) with 95% confidence intervals (CIs) to investigate the effect of GLP-1 receptor agonists on the renal protection. The outcomes were a composite renal outcome, estimated glomerular filtration rate (eGFR) decrease, new macroalbuminuria, doubling of serum creatinine, end-stage renal disease (ESRD) and renal death. We also checked the composite renal outcome of the patient subgroups based on the structural source of human GLP-1 or exendin-4. Among the 12 articles screened, seven studies involving 48101 patients met pre-specified criteria and were included. In general, the use of GLP-1 receptor agonists reduced the risk of the composite renal outcome by 17% (RR 0·83 95% CI 0·79-0·88 P < 0·00001), with no significant interaction in subgroups analysis (P 0.66) the risk of new-onset of persistent macroalbuminuria was reduced by 25% (RR 0·75 95%CI 0·69-0·81 P < 0·00001) compared to placebo. However, GLP-1 receptor agonists had no significant effect on eGFR decrease (RR 0·92 95% CI 0·83-1.01 P 0·09), doubling of serum creatinine (RR 0·97 95% CI 0·78-1.21 P 0·79), or end-stage renal disease (RR 0·81 95% CI 0·62-1.06 P 0·12) compared to placebo or insulin glargine (AWARD-7) in patients with type 2 diabetes. GLP-1 receptor agonists, regardless of their structural homology, have significant benefits in reducing the risk of the composite renal outcome, especially in new macroalbuminuria compared with placebo or insulin glargine in patients with type 2 diabetes.

Metformin use is associated with a lower risk of rotator cuff disease in patients with Type 2 diabetes mellitus.

Metformin has been mentioned to be protective against inflammation, degeneration, and oxidative stress, conditions that are associated with rotator cuff disease. To access the association between metformin use and risk of rotator cuff disease in patients with type 2 diabetes mellitus (DM). This was a retrospective cohort study utilizing Taiwan National Health Insurance Research Database between January 1, 2000, and December 31, 2012 to retrieved participants. Metformin and propensity score matched never metformin users were determined at baseline (between the date of onset of DM and the index date), and followed to December 31, 2013. Propensity scores were adopted to address measurable confounders (including demographic variables, Diabetes Complications Severity Index, relevant comorbidities and co-medication). A multivariable Cox proportional hazards regression model was applied to estimate the adjusted hazard ratios (HRs) for the risk of the first diagnosis of rotator cuff disease on the full cohort and on the propensity score matched cohort. In the propensity score matched cohort, a total of 34,964 individuals (19,416 55.5% men), 17,482 individuals were taking metformin, 559 3.2% of whom developed rotator cuff disease. Incidence of rotator cuff disease was 4.51 per 10,000 person-months in the metformin users and 5.11 in the controls. Among metformin group, the aHR (95% CI) was 0.879 (0.784-0.984) after full adjustment. The potential beneficial effect on the risk of rotator cuff disease was consistently observed across all subgroups, including sex, age, concomitant other glucose lowering drugs, and level of Diabetes Complications Severity Index (all P for interaction > 0.050). Metformin use was associated with a lower risk of rotator cuff disease in patients with type 2 DM.

Prevalence and predictors of non-alcoholic steatohepatitis in subjects with morbid obesity and with or without type 2 diabetes.

To investigate the prevalence of biopsy-proven non-alcoholic steatohepatitis (NASH) in a cohort of patients with morbid obesity and with or without type 2 diabetes (T2D) and to find non-invasive predictors of NASH severity. We evaluated a cohort of 412 subjects (age 19-67 years, body mass index-BMI 44.98 kgm The prevalence of biopsy-proven NASH was 63% and 78% in subjects with obesity and without or with T2D, respectively. T2D doubled the risk of NASH OR 2.079 (95% IC1.31-3.29). The prevalence of NAFL increased with the increase of BMI, while there was an inverse correlation between BMI and NASH (r-0.145 p0.003). Only mild liver fibrosis was observed. HOMA-IR was positively associated with hepatocyte ballooning (r0.208, p<0.0001) and fibrosis (r0.159, p0.008). The NNA highlighted a specificity of 77.3% using HDL-cholesterol, BMI, and HOMA-IR as main determinants of NASH. Our data show a higher prevalence of NASH in patients with morbid obesity than reported in the literature and the pivotal role of T2D among the risk factors for NASH development. However, the inverse correlation observed between BMI and biopsy-proven NASH suggests that over a certain threshold adiposity can be somewhat protective against liver damage. Our model predicts NASH presence with high specificity, thus helping identifying subjects who should promptly undergo liver biopsy.

Adipocyte-specific ablation of the Ca

Sarcoendoplasmic reticulum Ca SERCA expression was measured in isolated human and mouse adipocytes as well as in whole mouse adipose tissue by Western blot and RT-qPCR. To test the significance of SERCA2 in adipocyte functionality and whole-body metabolism, we generated adipocyte-specific SERCA2 knockout mice. The mice were metabolically phenotyped by glucose tolerance and tracer studies, histological analyses, measurements of glucose-stimulated insulin release in isolated islets, and geneprotein expression analyses. We also tested the effect of pharmacological SERCA inhibition and genetic SERCA2 ablation in cultured adipocytes. Intracellular and mitochondrial Ca We demonstrate that SERCA2 is downregulated in white adipocytes from patients with obesity and type-2 diabetes as well as in adipocytes from diet-induced obese mice. SERCA2-ablated adipocytes display disturbed Ca Our data suggest causal links between reduced white adipocyte SERCA2 levels, deranged adipocyte Ca

Demographic and clinical characteristics of patients with type 1 diabetes mellitus initiating sodium-glucose cotransporter 2 inhibitors in Japan A real-world administrative database analysis.

To investigate the baseline demographic and clinical characteristics of patients with type 1 diabetes mellitus (T1DM) newly treated with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) as an add-on to insulin, or treated with insulin alone or in combination with oral anti-diabetic drugs other than an SGLT2i. Retrospective study using data from the JMDC database (December 21, 2018, to October 31, 2020). Included patients with T1DM treated with an SGLT2i (add-on to insulin) (n 1027) or with insulin (n 4320). Baseline demographic and clinical characteristics were summarized, and change in insulin dose and efficacy outcomes, including hemoglobin A1c (HbA1c) and body mass index (BMI), before and after the first SGLT2i or insulin prescription were evaluated. The SGLT2i add-on group had higher HbA1c and BMI than the insulin group. Daily insulin doses decreased from immediately before to after the first SGLT2i prescription. HbA1c and BMI improved from baseline to after the first SGLT2i prescription. This large real-world study reported the baseline demographic and clinical characteristics of patients with T1DM newly treated with an SGLT2i in Japan. The findings may guide the appropriate use of SGLT2i and support large-scale database studies in T1DM research.

Lipid-induced glucose intolerance is driven by impaired glucose kinetics and insulin metabolism in healthy individuals.

Hypertriglyceridemia is associated with an increased risk of type 2 diabetes. We aimed to comprehensively examine the effects of hypertriglyceridemia on major glucose homeostatic mechanisms involved in diabetes progression. In this randomized, cross-over, single-blinded study, two dual-labeled, 3-hour oral glucose tolerance tests were performed during 5-hour intravenous infusions of either 20 % Intralipid or saline in 12 healthy subjects (age 27.9 ± 2.6 years, 11 men, BMI 22.6 ± 1.4 kgm Mild acute hypertriglyceridemia impaired oral glucose tolerance (mean glucose 0.9 0.3, 1.5 mmolL, p 0.008) and whole-body insulin sensitivity (Matsuda index -1.67 -0.50, -2.84, p 0.009). Post-glucose hyperinsulinemia (mean insulin 99 17, 182 pmolL, p 0.009) resulted from reduced insulin clearance (-0.16 -0.32, -0.01 L min Our findings support a critical role for hypertriglyceridemia in the pathogenesis of type 2 diabetes in otherwise healthy individuals and dissect the glucose homeostatic mechanisms involved, encompassing insulin sensitivity, β cell function and oral glucose absorption.

The Diabetes Prevention Gap And Opportunities To Increase Participation In Effective Interventions.

To understand the current state of prediabetes burden and treatment in the US, we examined recent trends in prediabetes prevalence, testing, and access to preventive resources. We estimated 13.5 percent prevalence of diagnosed prediabetes in the overall US adult population, using national survey data. Although prediabetes prevalence increased by 4.8 percentage points from 2010 to 2020, access to preventive resources remained low. The most effective intervention for diabetes prevention, known as the National Diabetes Prevention Program, remained woefully undersupplied and underused. There are only 2,098 National Diabetes Prevention Program-recognized providers nationally, and only 3 percent of adults with prediabetes have participated in the program. We suggest three actions to augment prevention efforts increase payment for prevention interventions to avoid supply distortions, improve data integration and patient follow-up, and extend coverage and broaden access for preventive interventions. These actions, which would require policy-level changes, could lower the barriers to prevention.

Diabetes And The Fragmented State Of US Health Care And Policy.

Progress in the prevention and treatment of type 2 diabetes-the dominant form of diabetes-appears to have stalled in the US over the past decade, and diabetes-related morbidity has increased nationally. The most geographically and socioeconomically disadvantaged segments of the population have been especially hard hit, and interventions that reduce the risk for diabetes have not reached these populations. In this overview article we lay out how fragmentation in health policy and governance, payers and reimbursement design, and service delivery in the US has contributed to low accountability and coordination, and thus stagnation and persistent inequities. We also review the evidence regarding past, ongoing, and new reforms that may help address fragmentation, lower diabetes burdens, and narrow disparities.

Nonmedical Interventions For Type 2 Diabetes Evidence, Actionable Strategies, And Policy Opportunities.

This systematic review identified studies of nonmedical interventions designed to reduce risk for and improve clinical outcomes for type 2 diabetes. Specifically, this review sought to identify interventions that target structural racism and social determinants of health. To be included, studies were published in English published between database initiation and January 2022 conducted in the United States measured an intervention effect using a clinical trial, quasi-experimental, or pre-post design included a population of adults at risk for or with type 2 diabetes and targeted hemoglobin A1c levels, blood pressure, lipids, self-care, or quality of life as outcomes. The findings of our review indicate that interventions with targeted, multicomponent designs that combine both medical and nonmedical approaches can reduce risk for and improve clinical outcomes for type 2 diabetes. HbA1c levels improved significantly with the use of food supplementation with referral and diabetes support the use of financial incentives with education and skills training the use of housing relocation with counseling support and the integration of nonmedical interventions into medical care using the electronic medical record. Our findings demonstrate that the literature on nonmedical interventions designed to address relevant social factors and target structural racism is limited. The article offers actionable strategies and identifies policy opportunities for targeting structural inequalities and decreasing social risk among adults with type 2 diabetes.

Care Management For Patients With Type 2 Diabetes The Roles Of Nurses, Pharmacists, And Social Workers.

Managing patients with type 2 diabetes takes time. Clinicians in primary care, where most diabetes visits take place, lack that time. Planned visits by diabetes care managers-nurses, pharmacists, social workers, and other team members-assist clinicians and are associated with improved glycemic control. Particularly effective is care management featuring nurses or pharmacists adjusting medications without prior physician approval. Care management programs need to pay close attention to inequities in diabetes care and outcomes. The widespread implementation of diabetes care management in primary care faces several barriers lack of an adequate, diverse, trained care manager workforce regulations limiting care managers scope of practice and financial models not supportive of care management. Wide-ranging policies are needed to address these barriers. In particular, payment reform is needed to stimulate the spread of diabetes care management adding fee-for-service codes that adequately pay care managers for their work, adopting shared savings models that channel savings back to primary care, and increasing the percentage of health care spending dedicated to primary care. In this article we explore key questions around type 2 diabetes care management, review the published evidence, examine the barriers to its wider use, and describe policy solutions.

An Agonistic Monoclonal Antibody Targeting cMet Attenuates Inflammation and Up-Regulates Collagen Synthesis and Angiogenesis in Type 2 Diabetic Mice Wounds.

Diabetic wounds account for 25 to 50 percent of total diabetic health care costs annually, and present overall healing rates of less than 50 percent. Because delayed diabetic wound healing is associated with impaired fibroblast function, the authors hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody will promote diabetic wound healing by means of stable activation of hepatocyte growth factorcMet signaling. Two 6-mm dorsal wounds were created in each mouse (6-week-old, male BKS.Cg-Dock7 m Lepr db J n 5). After subcutaneous injections of agonist (20 mgkg) at 0 and 72 hours, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histologic and immunohistochemical analyses were performed at day 10 (cMet, α-smooth muscle actin, CD68, and transforming growth factor-β). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with or without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p4442 mitogen-activated protein kinase, p-mTOR, p-cMet, and ROCK-1 expression. The cMet agonistic monoclonal antibody-treated group showed 1.60-fold lower wound area ( p 0.027), 1.54-fold higher collagen synthesis ( p 0.001), and 1.79-fold lower inflammatory cell infiltration ( p 0.032) than the saline-treated control. The agonist increased cMet (1.86-fold p 0.029), α-smooth muscle actin (1.20-fold p 0.018), and vascular endothelial growth factor (1.68-fold, p 0.029) expression but suppressed CD68 (1.25-fold p 0.043), transforming growth factor-β (1.25-fold p 0.022), and matrix metalloproteinase-2 (2.59-fold p 0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold ( p 0.029) and activated the hepatocyte growth factorcMet pathway. Tyrosine kinase Met agonistic monoclonal antibody treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials. Although further clinical studies are necessary to evaluate its therapeutic efficacy, our study suggested that cMet agonistic monoclonal antibody can be the alternative modality in order to improve wound healing cascade in diabetic foot patients.

Hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium benth leaf in type 2 diabetic rats via fetuin-A and tumor necrosis factor-alpha.

This study assessed the hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium Benth on diabetes-induced type 2 rats via Fetuin-A and tumor necrosis factor-alpha (TnF-α). In a standard procedure, the flavonoid-rich extract was prepared. For experimental rats, streptozotocin was injected intraperitoneally (45 mgkg body weight) to induce diabetes mellitus. Following this, rats were given 5% of glucose water for 24 h. Hence, the animals were randomly divided into five groups of ten rats each, consisting of non-diabetic rats, diabetic controls, diabetic rats treated with low and high doses of flavonoid rich-extracts from Gongronema latifolium leaf (FREGL) (13 and 26 mgkg, respectively), and diabetic rats treated with 200 mgkg of metformin glibenclamide orally for 3 weeks. Afterwards, the animals were sacrificed, blood and liver were harvested to evaluate different biochemical parameters, hepatic gene expressions and histological examinations. The results revealed that FREGL (especially at the low dose) significantly (p < 0.05) reduced alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphate (ALP) activities, lipid peroxidation level, as well as relative gene expressions of fetuin-A and TNF-α in diabetic rats. Furthermore, diabetic rats given various doses of FREGL showed an increase in antioxidant enzymes and hexokinase activity, as well as glucose transporters (GLUT 2 and GLUT 4), and glycogen levels. In addition, histoarchitecture of the liver of diabetic rats administered FREGL (especially at the low dose) was also ameliorated. Hence, FREGL (particularly at a low dose) may play a substantial role in mitigating the hepatopathy complication associated with diabetes mellitus.

Development of a Primary Human Intestinal Epithelium Enriched in L-Cells for Assay of GLP-1 Secretion.

Type 2 diabetes mellitus is a chronic disease associated with obesity and dysregulated human feeding behavior. The hormone glucagon-like peptide 1 (GLP-1), a critical regulator of body weight, food intake, and blood glucose levels, is secreted by enteroendocrine L-cells. The paucity of L-cells in primary intestinal cell cultures including organoids and monolayers has made assays of GLP-1 secretion from primary human cells challenging. In the current paper, an analytical assay pipeline consisting of an optimized human intestinal tissue construct enriched in L-cells paired with standard antibody-based GLP-1 assays was developed to screen compounds for the development of pharmaceuticals to modulate L-cell signaling. The addition of the serotonin receptor agonist Bimu 8, optimization of R-spondin and Noggin concentrations, and utilization of vasoactive intestinal peptide (VIP) increased the density of L-cells in a primary human colonic epithelial monolayer. Additionally, the incorporation of an air-liquid interface culture format increased the L-cell number so that the signal-to-noise ratio of conventional enzyme-linked immunoassays could be used to monitor GLP-1 secretion in compound screens. To demonstrate the utility of the optimized analytical method, 21 types of beverage sweeteners were screened for their ability to stimulate GLP-1 secretion. Stevioside and cyclamate were found to be the most potent inducers of GLP-1 secretion. This platform enables the quantification of GLP-1 secretion from human primary L-cells and will have broad application in understanding L-cell formation and physiology and will improve the identification of modulators of human feeding behavior.

InsulinAPP application protocol for the inpatient management of type 2 diabetes on a hospitalist-managed ward a retrospective study.

We assessed metrics related to inpatient glycemic control using InsulinAPP, an application available for free in Brazil, on the hospitalist-managed ward of our hospital. We performed a retrospective study of patients with type 2 diabetes (T2D) admitted from November 2018 to October 2019. InsulinAPP recommends NPH and regular insulins three times a day, in bolus-correction or basal-bolus schemes. Parameters that included BG within range of 70-180 mgdL, insulin treatment regimen and frequency of hypoglycemia were evaluated. A total of 147 T2D individuals (23% medicine and 77% surgery) were included (mean age 62.3 ± 12.7 years, HbA1c 8.3 ± 3.0%). The initial insulin regimen was 50% bolus-correction, 47% basal-bolus and 3% with sliding scale insulin. During hospitalization, 71% patients required a bolus-basal regimen. In the first 10 days of the protocol, 71% BG measurements were between 70-180 mgdL and 26% patients experienced one or more episodes of hypoglycemia < 70 mgdL, and 5% with BG < 54 mgdL. The results of this retrospective study indicate the InsulinAPP application using human insulin formulations was effective and safe for the management of hyperglycemia on a hospitalist-managed ward, with more than 70% BG measurements within the therapeutic range and a low rate of hypoglycemia.

COMPARATIVE PHARMACOECONOMIC ANALYSIS OF SELF-CONTROL OF DIABETES MELLITUS USING GLUCOMETERS.

The aim To pharmacoeconomic analysis of direct medical costs for self-control of diabetes in Ukraine, Moldova and Georgia. Our observational, cross-sectional study aims at finding out the real costs of covering expenses in order to make decisions on the reimbursement of self-control means. Materials and methods 1) International and national clinical guidelines for diabetes 2) information about the prices of glucometers, test strips from online pharmacy services. Systematization, generalization and pharmacoeconomic analysis of direct medical costs were used in the study. Results Based on the generalization of recommendations on the frequency of blood glucose control, 3 scenarios were identified, according to which the costs were calculated Type 1 diabetes Type 2 diabetes (insulin therapy) Type 2 diabetes (oral hypoglycemic therapy). The authors conducted pharmacoeconomic analysis of direct medical costs for self-control of DM for PWD in Ukraine, Moldova and Georgia. The study shows that the lowest cost of self-control is provided in Ukraine, in addition, Ukraine has a wider choice of glucometers and test strips. It was revealed that the pharmaceutical markets for glycometers in the three countries depends on the import of equipment. Conclusions It is advisable to introduce in Ukraine the reimbursement of self-control devices, namely, glucometers and test strips for all categories of PWD, which will contribute to self-control and, as a result, will be able to prevent the development of complications. Certification of continuous glucose monitoring systems will increase access to new technologies that are already widely used in many countries.

Foot Self-Care Behaviour among People with Type 2 Diabetes mellitus Living in Rural Underserved Area of North India A Community-Based Cross-Sectional Study.

The objective of this study was to ascertain the foot self-care behaviour and its associated factors among people with type 2 diabetes mellitus (T2DM) living in the rural resource-constrained health setting of Punjab, North India. A community based cross sectional study was undertaken in the randomly selected underserved rural area of District Fatehgarh Sahib, Punjab, North India. A pre-validated Nottingham Assessment of Functional Footcare (NAFF) scale was administered to assess foot self-care behaviour, and participants were classified based on the percentage of a maximum possible score of 84 on the scale, as poor, if the score was <50%, satisfactory if score 50%-70% and >70% good foot self-care behaviour. A total of 700 participants responses were recorded. The study results revealed that 84% (588) of the respondents had poor, 16% (112) had satisfactory, and none were following good foot self-care behaviour. An outcome of multivariable logistics regression suggested satisfactory foot self-care behaviour was significantly associated with foot self-care education, with an adjusted odds ratio (aOR) of 2.83 (95%, CI1.62 - 4.93

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism.

Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. The pharmacokinetics of 10 mgkg ROS with 100200 mgkg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. The The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.