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Altered Nutrient Uptake Causes Mitochondrial Dysfunction in Senescent CD8

Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8

Exploration of natural flavones bioactivity and bioavailability in chronic inflammation induced-type-2 diabetes mellitus.

Diabetes, being the most widespread illness, poses a serious threat to global public health. It seems that inflammation plays a critical role in the pathophysiology of diabetes. This review aims to demonstrate a probable link between type 2 diabetes mellitus (T2DM) and chronic inflammation during its development. Additionally, the current review examined the bioactivity of natural flavones and the possible molecular mechanisms by which they influence diabetes and inflammation. While natural flavones possess remarkable anti-diabetic and anti-inflammatory bioactivities, their therapeutic use is limited by the low oral bioavailability. Several factors contribute to the low bioavailability, including poor water solubility, food interaction, and unsatisfied metabolic behaviors, while the diseases (diabetes, inflammation, etc.) causing even less bioavailability. Throughout the years, different strategies have been developed to boost flavones bioavailability, including structural alteration, biological transformation, and innovative drug delivery system design. This review addresses current advancements in improving the bioavailability of flavonoids in general, and flavones in particular. Clinical trials were also analyzed to provide insight into the potential application of flavonoids in diabetes and inflammatory therapies.

A centennial review of discoveries and advances in diabetes Children and youth.

Diabetes is an increasingly common chronic metabolic disorder in children worldwide. The discovery of insulin in 1921 resulted in unprecedented advancements that improved the lives of children and youth with diabetes. The purpose of this article is to review the history of diabetes in children and youth over the last century and its implications for future developments in the field. We identified 68 relevant events between 1921 and 2021 through literature review and survey of pediatric endocrinologists. Basic research milestones led to the discovery of insulin and other regulatory hormones, established the normal physiology of carbohydrate metabolism and pathophysiology of diabetes, and provided insight into strategies for diabetes prevention. While landmark clinical studies were initially focused on adult diabetes populations, later studies assessed etiologic factors in birth cohort studies, evaluated technology use among children with diabetes, and investigated pharmacologic management of youth type 2 diabetes. Technological innovations culminated in the introduction of continuous glucose monitoring that enabled semi-automated insulin delivery systems. Finally, professional organizations collaborated with patient groups to advocate for the needs of children with diabetes and their families. Together, these advances transformed type 1 diabetes from a terminal illness to a manageable disease with near-normal life expectancy and increased our knowledge of type 2 diabetes and other forms of diabetes in the pediatric population. However, disparities in access to insulin, diabetes technology, education, and care support remain and disproportionately impact minority youth and communities with less resources. The overarching goal of diabetes management remains promoting a high quality of life and improving glycemic management without undermining the psychological health of children and youth living with diabetes.

Glucose metabolism controls human γδ T-cell-mediated tumor immunosurveillance in diabetes.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cancer. The effect of glucose metabolism on γδ T cells and their impact on tumor surveillance remain unknown. Here, we showed that high glucose induced Warburg effect type of bioenergetic profile in Vγ9Vδ2 T cells, leading to excessive lactate accumulation, which further inhibited lytic granule secretion by impairing the trafficking of cytolytic machinery to the Vγ9Vδ2 T-cell-tumor synapse by suppressing AMPK activation and resulted in the loss of antitumor activity in vitro, in vivo and in patients. Strikingly, activating the AMPK pathway through glucose control or metformin treatment reversed the metabolic abnormalities and restored the antitumor activity of Vγ9Vδ2 T cells. These results suggest that the impaired antitumor activity of Vγ9Vδ2 T cells induced by dysregulated glucose metabolism may contribute to the increased cancer risk in T2DM patients and that metabolic reprogramming by targeting the AMPK pathway with metformin may improve tumor immunosurveillance.

Risk trajectories of complications in over one thousand newly diagnosed individuals with type 2 diabetes.

Although the increased risk of complications of type 2 diabetes (T2D) is well known, there is still little information about the long-term development of comorbidities in relation to risk factors. The purpose of the present study was to describe the risk trajectories of T2D complications over time in an observational cohort of newly diagnosed T2D patients, as well as to evaluate the effect of common risk factors on the development of comorbidities. This national cohort study investigated individuals with T2D in the Swedish National Diabetes Register regarding prevalence of comorbidities at the time of diagnosis, and the incidence of cardiovascular disease (CVD), chronic kidney disease (CKD) and heart failure in the entire patient cohort and stratified by HbA1c levels and age at baseline. Multivariable Cox regressions were used to evaluate risk factors predicting outcomes. We included 100,878 individuals newly diagnosed with T2D between 1998 and 2012 in the study, with mean 5.5 years follow-up (max 17 years). The mean age at diagnosis was 62.6 ± SD12.5 years and 42.7% of the patients were women. Prevalent CVD was reported for 17.5% at baseline. Although the prevalence of comorbidities was generally low for individuals 50 years or younger at diagnosis, the cumulative incidence of the investigated comorbidities increased over time. Newly diagnosed CVD was the most common comorbidity. Women were shown to have a lower risk of developing comorbid conditions than men. When following the risk trajectory of comorbidities over a period of up to 15 years in individuals with type 2 diabetes, we found that all comorbidities gradually increased over time. There was no distinct time point when onset suddenly increased.

Turner syndrome French National Diagnosis and Care Protocol (NDCP National Diagnosis and Care Protocol).

Turner syndrome (TS ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 12500 liveborn girls. The most frequently observed karyotypes are 45,X (40-50%) and the 45,X46,XX mosaic karyotype (15-25%). Karyotypes with an X isochromosome (45,X46,isoXq or 45,X46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweightobesity, glucose intolerancetype 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.

Adaptation of diabetes prevention program for Chinese Americans - a qualitative study.

Studies have demonstrated that a culturally and linguistically tailored Diabetes Prevention Program (DPP) can be effective in reducing diabetes risk in Chinese Americans. The purpose of this study was to explore the cultural and linguistic acceptability of the Centers for Disease Control and Preventions Prevent T2 curriculum in an online format in the Chinese American community in New York City (NYC). Three focus groups among a total of 24 Chinese Americans with prediabetes and one community advisory board (CAB) meeting with 10 key stakeholders with expertise in diabetes care and lifestyle interventions were conducted. Each focus group lasted approximately 1 to 1.5 h. All groups were moderated by a bilingual moderator in Chinese. The sessions were audiotaped, transcribed and translated to English for analysis. Using Atlas.ti software and open coding techniques, two researchers analyzed transcripts for thematic analysis. Five key themes were identified barriers to behavioral changes, feedback on curriculum content and suggestions, web-based intervention acceptability, web-based intervention feasibility, and web-based intervention implementation and modifications. Participants with prediabetes were found to have high acceptability of web-based DPP interventions. Suggestions for the curriculum included incorporating Chinese American cultural foods and replacing photos of non-Asians with photos of Asians. Barriers included lack of access to the internet, different learning styles and low technology self-efficacy for older adults. Although the acceptability of web-based DPP in the Chinese American community in NYC is high, our focus group findings indicated that the major concern is lack of internet access and technical support. Providing support, such as creating an orientation manual for easy online program access for future participants, is important.

Dietary antioxidant consumption and the risk of type 2 diabetes in South Korean adults a prospective cohort study based on the Health Examinees study.

Antioxidants are common dietary compounds with multiple health benefits. This study aimed to identify the association between dietary antioxidant consumption and the incidence of type 2 diabetes (T2D) mellitus (defined using the Korean Diabetes Association criteria) in South Korean adults. Baseline and follow-up data from the Health Examinees (HEXA) study, a large-scale community-based genomic cohort study conducted in South Korea SETTING A South Korean community. A total of 20 594 participants, aged 40-79 years, who participated in the baseline and follow-up surveys of the HEXA study were included. After an average of 5 years of follow-up, there were 332 men and 360 women with T2D. Participants with the highest total flavonoid consumption (Q5) had a lower risk of T2D (men HR 0.63 95% CI 0.42 to 0.93 p value for trend0.0169 and women HR 0.54 95% CI 0.438 to 0.78 p value for trend0.0001) than those with the lowest consumption (Q1). Dietary total antioxidant capacity was significantly inversely associated with the development of T2D mellitus in women participants alone (HR 0.58 95% CI 0.40 to 0.83 p value for trend0.0004). Stratified analyses according to age and body mass index (BMI) showed that dietary total flavonoid consumption and total antioxidant capacity had a negative association with the development of T2D in women aged >52 years and women with BMI >25 kgm Dietary flavonoid consumption and total antioxidant capacity were associated with a lower risk of T2D in South Korean adults, especially in women aged >52 years and overweight. The findings of this study may provide reference data for the modification of dietary guidelines for South Koreans.

Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) protocol for a randomised controlled trial.

The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM. The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size. The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-22022EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. ClinicalTrials.gov, NCT05237219.

Association of hemoglobin A1c time in range with risk for diabetes complications.

We assessed the association between hemoglobin A1c time in range (A1c TIR), based on unique patient-level A1c target ranges, with risks of developing microvascular and macrovascular complications in older adults with diabetes. We used a retrospective observational study design and identified patients with diabetes from the Department of Veterans Affairs (n397 634). Patients were 65 years and older and enrolled in Medicare during the period 2004-2016. Patients were assigned to individualized A1c target ranges based on estimated life expectancy and the presence or absence of diabetes complications. We computed A1c TIR for patients with at least four A1c tests during a 3-year baseline period. The association between A1c TIR and time to incident microvascular and macrovascular complications was studied in models that included A1c mean and A1c SD. We identified 74 016 patients to assess for incident microvascular complications and 89 625 patients to assess for macrovascular complications during an average follow-up of 5.5 years. Cox proportional hazards models showed lower A1c TIR was associated with higher risk of microvascular (A1c TIR 0% to <20% HR1.04 95%) and macrovascular complications (A1c TIR 0% to <20% HR1.07 95%). A1c mean was associated with increased risk of microvascular and macrovascular complications but A1c SD was not. The association of A1c TIR with incidence and progression of individual diabetes complications within the microvascular and macrovascular composites showed similar trends. Maintaining stability of A1c levels in unique target ranges was associated with lower likelihood of developing microvascular and macrovascular complications in older adults with diabetes.

Molecular basis of the anchoring and stabilization of human islet amyloid polypeptide in lipid hydroperoxidized bilayers.

The molecular structure of membrane lipids is formed by mono- or polyunsaturations on their aliphatic tails that make them susceptible to oxidation, facilitating the incorporation of hydroperoxide (R-OOH) functional groups. Such groups promote changes in both composition and complexity of the membrane significantly modifying its physicochemical properties. Human Langerhans islets amyloid polypeptide (hIAPP) is the main component of amyloid deposits found in the pancreas of patients with type-2 diabetes (T2D). hIAPP in the presence of membranes with oxidized lipid species accelerates the formation of amyloid fibrils or the formation of intermediate oligomeric structures. However, the molecular bases at the initial stage of the anchoring and stabilization of the hIAPP in a hydroperoxidized membrane are not yet well understood. To shed some light on this matter, in this contribution, three bilayer models were modeled neutral (POPC), anionic (POPS), and oxidized (POPC

Greater intake of the MEDI diet is associated with better cognitive trajectory in older adults with type 2 diabetes.

To determine associations of three dietary patterns (Mediterranean (MEDI) diet, the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean- DASH Intervention for Neurodegenerative Delay (MIND) diet) with cognitive decline in older adults with type 2 diabetes mellitus (T2D). This is a longitudinal observational study. Participants (N 960) from the Israel Diabetes and Cognitive Decline (IDCD) study were included in this study. A multivariable-adjusted model including all three dietary patterns concurrently was developed to investigate their independent effect on cognitive decline. The mean follow up was 4.1 ± 2.1 years. While high adherence to both the MIND and the MEDI diet was associated with a slower decline, in the multivariable model only the associations of higher MEDI diet intake with greater decline in global cognition and in executive functions remained significant (β 0.013, SE 0.006 P 0.042 β 0.001, SE 0.008, Pv 0.023 respectively). In older adults with T2D, adherence to the MEDI is related to better cognitive trajectory. Diet is a meaningful factor in the path linking T2D and cognition.

Celastrol inhibits TXNIP expression to protect pancreatic β cells in diabetic mice.

Celastrol (CEL) has a great potential in the treatment of a wide variety of metabolic diseases. However, whether CEL protects pancreatic β cells and its underlying mechanism are not yet clear. This study investigates to determine the effects of CEL on the pathogenesis of pancreatic β cells damage. C57BLKSLepr Our results showed that CEL at the high dose (CEL-H, 0.2 mgkg) protects dbdb mice against increased body weight and blood glucose. CEL-H inhibits pancreatic β cell apoptosis in dbdb mice and high glucose-induced INS-1 cells. CEL-H also reduced IL-1β production in islet macrophages. The further study found that CEL suppressed TXNIP expression and NLRP3 inflammasome activation in pancreatic β cells and islet macrophages. Importantly, the inhibitory effect of CEL on pancreatic β cell apoptosis and IL-1β production was also dependent on TXNIP. Mechanically, CEL inhibits Txnip transcription by promoting the degradation of ChREBP. Celastrol inhibits TXNIP expression to protect pancreatic β cells in vivo and in vitro. Our research pointed out another mechanism by which celastrol functions under the condition leptin signaling is ineffective.

Content Validity of Patient-Reported Outcome Measures Developed for Assessing Health-Related Quality of Life in People with Type 2 Diabetes Mellitus a Systematic Review.

We aimed to systematically evaluate the content validity of patient-reported outcome measures (PROMs) specifically developed to measure (aspects of) health-related quality of life (HRQOL) in people with type 2 diabetes. A systematic review was performed in PubMed and Embase of PROMs measuring perceived symptoms, physical function, mental function, social functionparticipation, and general health perceptions, and that were validated to at least some extent. Content validity (relevance, comprehensiveness, and comprehensibility) was evaluated using COSMIN methodology. We identified 54 (different versions of) PROMs, containing 150 subscales. We found evidence for sufficient content validity for only 41150 (27%) (subscales of) PROMs. The quality of evidence was generally very low. We found 66 out of 150 (44%) (subscales of) PROMs with evidence for either insufficient relevance, insufficient comprehensiveness, or insufficient comprehensibility. For measuring diabetes-specific symptoms, physical function, mental function, social functionparticipation, and general health perceptions, we identified one to 11 (subscales of) PROMs with sufficient content validity, although quality of the evidence was generally low. For measuring depressive symptoms, no PROM with sufficient content validity was identified. For each aspect of HRQL, we found at least one PROM with sufficient content validity, except for depressive symptoms. The quality of the evidence was mostly very low.

A Critical Review on Role of Available Synthetic Drugs and Phytochemicals in Insulin Resistance Treatment by Targeting PTP1B.

Insulin resistance (IR) is a condition of impaired response of cells towards insulin. It is marked by excessive blood glucose, dysregulated insulin signalling, altered pathways, damaged pancreatic β-cells, metabolic disorders, etc. Chronic hyperglycemic conditions leads to type 2 diabetes mellitus (T2DM) which causes excess generation of highly reactive free radicals, causing oxidative stress, further leading to development and progression of complications like vascular dysfunction, damaged cellular proteins, and DNA. One of the causes for IR is dysregulation of protein tyrosine phosphatase 1B (PTP1B). Advancements in drug therapeutics have helped people manage IR by regulating PTP1B, however have been reported to cause side effects. Therefore, there is a growing interest on usage of phytochemical constituents having IR therapeutic properties and aiding to minimize these complications. Medicinal plants have not been utilized to their full potential as a therapeutic drug due to lack of knowledge of their active and effective chemical constituents, mode of action, regulation of IR parameters, and dosage of administration. This review highlights phytochemical constituents present in medicinal plants or spices, their potential effectiveness on proteins (PTP1B) regulating IR, and reported possible mechanism of action studied on in vitro models. The study gives current knowledge and future recommendations on the above aspects and is expected to be beneficial in developing herbal drug using these phytochemical constituents, either alone or in combination, for medication of IR and diabetes.

Predictive Efficiency of Prediabetes for Diabetes Among Chinese Middle-Aged and Older Populations a 5-Year National Prospective Cohort Study.

Limited studies have explored the predictive efficiency of prediabetes based on two definitions for diabetes among Chinese middle-aged and older populations with prediabetes. To evaluate the predictive efficiency of prediabetes based on two definitions for diabetes and the clinical and public health benefit in Chinese middle-aged and older populations. A 5-year cohort study from the China Health and Retirement Longitudinal Study. A total of 5208 participants who had blood sample data at baseline in 2011. The exposure was prediabetes based on American Diabetes Association (ADA) and World Health Organization (WHO) definition. The main outcome was incident diabetes. The ability of prediabetes for predicting diabetes was assessed by sensitivity, specificity, positive predictive value, and negative predictive value. Cox proportional hazards regression was used to explore the associations between prediabetes and the 5-year risk of diabetes and all-cause mortality. Among those with prediabetes according to the ADA definition, only 426 (15.45%) with baseline prediabetes progressed to total diabetes, while according to the WHO definition, 208 (21.89%) progressed to total diabetes. In terms of the ability of predicting the incident total diabetes in 5 years, the ADA definition has a higher sensitivity than the WHO definition (70.76% versus 34.55%, P < 0.001), while the WHO definition has a higher specificity than the ADA definition (84.09% versus 49.35%, P < 0.001). Positive predictive values based on the two definitions were low (< 24%) negative predictive values were high (> 90%). Neither definition of prediabetes is robust for predicting diabetes development in Chineses middle-aged and older populations.

Effects of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) on Cardiac Structure and Function A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

Recent trials suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a cardioprotective role by reducing major adverse cardiac events, stroke mortality and heart failure-related hospitalisations. We examined whether and how GLP-1RAs affect cardiac function in cardiovascular and metabolic diseases including type 2 diabetes, heart failure and post-myocardial infarction. In this PRISMA-adherent systematic review and meta-analysis, three databases were searched from inception to July 2021 and registered on PROSPERO (CRD42021259661). 20 reports of 19 randomized placebo-controlled trials including 2062 participants were meta-analyzed. Among type 2 diabetes patients, GLP-1RA resulted in improved systolic function measured by circumferential strain (mean difference MD -5.48 95% CI -10.47 to -0.49 P 0.03 I GLP-1RA drugs may improve systolic and diastolic function in type 2 diabetes and reduce infarct size post-acute myocardial infarction with no demonstrable effect on cardiac function in heart failure. Tailored recommendations for the use of GLP-1RAs for cardioprotection should be considered for each patients condition.

An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

Type 2 diabetes (T2D) is a complex metabolic disorder with no cure and high morbidity. Exposure to inorganic arsenic (iAs), a ubiquitous environmental contaminant, is associated with increased T2D risk. Despite growing evidence linking iAs exposure to T2D, the factors underlying inter-individual differences in susceptibility remain unclear. This study examined the interaction between chronic iAs exposure and body composition in a cohort of 75 Diversity Outbred mice. The study design mimics that of an exposed human population where the genetic diversity of the mice provides the variation in response, in contrast to a design that includes untreated mice. Male mice were exposed to iAs in drinking water (100 ppb) for 26 weeks. Metabolic indicators used as diabetes surrogates included fasting blood glucose and plasma insulin (FBG, FPI), blood glucose and plasma insulin 15 min after glucose challenge (BG15, PI15), homeostatic model assessment for Formula see text-cell function and insulin resistance (HOMA-B, HOMA-IR), and insulinogenic index. Body composition was determined using magnetic resonance imaging, and the concentrations of iAs and its methylated metabolites were measured in liver and urine. Associations between cumulative iAs consumption and FPI, PI15, HOMA-B, and HOMA-IR manifested as significant interactions between iAs and body weightcomposition. Arsenic speciation analyses in liver and urine suggest little variation in the mices ability to metabolize iAs. The observed interactions accord with current research aiming to disentangle the effects of multiple complex factors on T2D risk, highlighting the need for further research on iAs metabolism and its consequences in genetically diverse mouse strains.

Lower Extremity Amputee Outcomes with Reference to Co-morbidities.

Lower extremity amputation related to diabetes is a serious outcome, which can have devastating effects on the patient and family. The epidemiology of amputations has recently been used as a possible measure of the adequacy of medical prevention and treatment of diabetes and diabetic foot complications. To report on patients undergoing amputations at one medical center in Israel, their co-morbidities, and the outcomes. A retrospective chart study was conducted of amputees operated between 1 September 2017 and 30 September 2018. The study population comprised 72 patients who had major amputations for diabetes andor ischemia, mean age 72 ± 10 years, 74% males, 93% with type 2 diabetes. Mean age corrected Charlson Comorbidity Index was 8.2 ± 2.1 with 90% (65 patients) presenting with a score of 6 or higher. Before the recent deterioration, fewer than 20% of the patients exited their home routinely and 24% had an official diagnosis of dementia. There were 31 below knee amputations (BKA) and 41 above knee amputations (AKA). The 30-day, 3-month, 1-year, and 2-year mortality rates were 15.3%, 27.8%, 43.1%, and 54.2% respectively. Median survival period was 20 months. Survival after AKA was 13.4 ± 20, which was significantly less than after BKA (25.4 ± 2.7, P 0.097). Factors other than the quality of management of patients with diabetes and complications may contribute to amputation rates thus, making speculations from international comparisons of raw amputation rates problematic. This population was less healthy than reported in most studies.

Reactive Oxygen Species Contributes to Type 2 Diabetic Neuropathic Pain via the Thioredoxin-Interacting Protein-NOD-Like Receptor Protein 3- N -Methyl-D-Aspartic Acid Receptor 2B Pathway.

The number of patients with diabetic neuropathic pain (DNP) continues to increase, but available treatments are limited. This study aimed to examine the influence of reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NOD-like receptor protein 3 (NLRP3)- N -methyl-D-aspartic acid receptor 2B (NR2B) pathway on type 2 DNP. Male Sprague-Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks. Then, rats were intraperitoneally injected with streptozotocin (STZ, 35 mgkg) to induce type 2 diabetes mellitus in rats. Diabetic rats with <85% of their basic levels in mechanical withdrawal threshold and thermal withdrawal latency were classified as DNP rats on day 14 after STZ injection. DNP rats were treated with ROS scavenger N-tert-Butyl-α-phenylnitrone (PBN, 100 mg·kg -1 ·d -1 ) or TXNIP small interfering ribonucleic acid (10 μgd) once daily for 14 days. The level of ROS, protein levels of NLRP3, TXNIP, cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β (IL-1β), NR2B phosphorylation at Tyr1472 (p-NR2B), total NR2B (t-NR2B), and distribution of NLRP3 in the spinal cord were examined. In vitro experiments, BV2 cells and PC12 cells were individually cultured and cocultured in a high-glucose environment (35 mmolL D-glucose). The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, and IL-1β in BV2 cells, and p-NR2B, t-NR2B in PC12 cells were detected. The level of ROS was detected by the flow cytometry approach. The protein levels were detected by the Western blot technique. The location of NLRP3 was observed by immunofluorescent staining. The interaction between TXNIP and NLRP3 was detected by coimmunoprecipitation assay. The level of spinal ROS increased in DNP rats. The mechanical allodynia and thermal hyperalgesia of DNP rats were alleviated after systemic administration of PBN. This administration decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B and the coupling of TXNIP to NLRP3 in spinal cords of DNP rats. Furthermore, knockdown of spinal TXNIP alleviated nociceptive hypersensitivity and decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B in DNP rats. The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, IL-1β, the coupling of TXNIP to NLRP3, and the IL-1β secretion increased in BV2 cells, and the protein expression of p-NR2B increased in cocultured PC12 cells in a high-glucose environment. All of these in vitro effects were significantly blocked after treatment of PBN. Our findings suggest that spinal ROS can contribute to type 2 DNP through TXNIP-NLRP3-NR2B pathway.

Abdominal aortic calcification is associated with Fibrosis-4 index and low body mass index in type 2 diabetes patients A retrospective cross-sectional study.

This study aimed to clarify the nature of the relationship between the abdominal aortic calcification (AAC) grade and the presence of cardiovascular diseases, and determine factors related to AAC grade in people with type 2 diabetes mellitus. This retrospective cross-sectional study enrolled 264 inpatients with type 2 diabetes mellitus. The AAC score and length were measured using the lateral abdominal radiographs. Logistic regression models were used to assess the associations between AAC scoreslengths and the presence of coronary artery disease (CAD), cerebral infarction (CI) and peripheral artery disease (PAD). The correlation between AAC scoreslengths and other clinical factors were evaluated using linear regression models. The AAC score was significantly correlated with prevalent CAD and CI independent of age and smoking, but not with the prevalence of PAD. AAC length was not significantly correlated with the presence of CAD, CI or PAD however, the sample size was insufficient to conclude, probably due to low prevalence. Both the AAC score and length were correlated inversely with body mass index (BMI) and, with the Fibrosis-4 (Fib-4) index >2.67 these correlations were significant after adjusting for cardiovascular risk factors and BMI, although AAC was not associated with ultrasonography-diagnosed fatty liver. There was a significant interaction between BMI and Fib-4 index lower BMI and Fib-4 index >2.67 showed a synergistic association with high AAC grade. AAC score is associated with CAD and CI morbidity in participants with type 2 diabetes mellitus. Low BMI and Fib-4 index >2.67 can be valuable indicators of AAC in people with type 2 diabetes mellitus.

Similar Blood Glucose Pattern with Highest Peak at Minute 45 on Oral Glucose Tolerance Test Despite Higher Fasting Insulin and Insulin Resistance in Healthy Obese than Non-Obese Subject.

Obesity increase the risk for type 2 diabetes through induction of insulin resistance. Diagnosis of diabetes were based on blood glucose level. However, insulin resistance may had happened far before diagnosis itself. This study aimed to compare fasting insulin level, insulin resistance, and blood glucose pattern during oral glucose load in healthy obese and non-obese subject. This semi-experimental study was conducted at Department of Internal Medicine, Sanglah Hospital, Denpasar. Sixteen subjects in each obese and non-obese group were matched by age and sex. Obesity was defined based on body mass index (BMI) of ≥25kgm2 and waist circumference (WC) ≥80cm (female) or ≥90cm (male). The non-obese group was defined by BMI of 18-25kgm2 and WC <80cm (female) or <90cm (male). Fasting insulin level and blood glucose was measured at minute 0, 15, 30, 45, 60, 75, 90, 120 after glucose load of 75 grams. Insulin resistance was calculated based on homeostasis model assessment of insulin resistance (HOMA-IR) with the following formula HOMA-IR (FPI×FPG)22.5. Normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subject was defined by American Diabetes Association (ADA) criteria. Fasting insulin level in obese subjects was higher than non-obese subjects with median 12.75 (range 3.70 - 41.30) vs 3.80 (1.80 - 36.80) µUmL, p0.041. HOMA IR was also higher in obese subjects compared to non-obese subjects 2.45 (0.70 - 8.00) vs 0.80 (0.40 - 8.50), p0.001. Fasting insulin level was correlated with BMI (r0.559, p0.001) and WC (r0.633, p<0.001). A significant correlation was also detected between HOMA IR with BMI (r0.528, p0.002) and WC (r0.600, p<0.001). Blood glucose pattern in four groups obese IGT, obese NGT, non-obese IGT, and non-obese NGT, were typically similar, in particular two peaks of blood glucose. The first peak was the highest blood glucose, shown in minute 45 in both obese and non-obese subjects. The second peak was lower than the first peak, found in minute 75 among NGT and minute 90 among IGT subject. Blood glucose level for each measurement point was consistently higher in obese than non-obese subjects. Fasting insulin level and HOMA-IR were higher in obese than in non-obese subjects. BMI and WC were significantly correlated with fasting insulin level and HOMA IR, so that high BMI and WC can be an earlier clinical sign of insulin resistance and prediabetes. Pattern of blood glucose level after oral glucose load were similar with two peaks, and blood glucose consistently higher in obese compared to non-obese subjects. The highest peak of blood glucose, shown in minute 45 in both obese and non-obese subjects.

MicroRNAs as biomarkers for monitoring cardiovascular changes in Type II Diabetes Mellitus (T2DM) and exercise.

MicroRNAs (miRNAs) have been shown to be altered in both CVD and T2DM and can have an application as diagnostic and prognostic biomarkers. miRNAs are released into circulation when the cardiomyocyte is subjected to injury and damage. Measuring circulating miRNA levels in human plasma may be of great potential use for measuring the extent of damage to cardiomyocytes and response to exercise. This review is aimed to highlight the potential application of miRNAs as biomarkers of CVD progression in T2DM, and the impact of exercise on recovery. The review aims to examine whether the health improvements following exercise in T2DM patients are reflective of changes in expression of plasma miRNAs. For this purpose, studies were identified from the literature that have established a correlation between diabetes, disease progression and plasma miRNA levels. We also reviewed studies which looked at the effect of exercise on plasma miRNA levels. The review identified miRNA signatures that are affected by T2DM and DHD and a subset of these miRNAs that are also affected by different types of exercise. This approach helped us to identify those miRNAs whose expression and function can be altered by regular bouts of exercise. miRNAs identified as part of this review can serve as tools to monitor the cardio-protective, anti-inflammatory and metabolic effects of exercise in people suffering from T2DM. Future research should focus on regulation of these miRNAs in T2DM and how they can be altered by appropriate exercise interventions. The online version contains supplementary material available at 10.1007s40200-022-01066-4.

Identification of bone metabolism disorders in patients with Alström and Bardet-Biedl syndromes based on markers of bone turnover and mandibular atrophy.

Causative variants in genes responsible for Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) cause damage to primary cilia associated with correct functioning of cell signaling pathways in many tissues. Despite differences in genetic background, both syndromes affect multiple organs and numerous clinical manifestations are common including obesity, retinal degeneration, insulin resistance, type 2 diabetes and many others. The aim of the study was to evaluate bone metabolism abnormalities and their relation to metabolic disorders based on bone turnover markers and presence of mandibular atrophy in patients with ALMS and BBS syndromes. In 18 patients (11 with ALMS and 7 with BBS aged 5-29) and in 42 age-matched ( Lower serum OC ( The identification of bone metabolism disorders in patients with ALMS and BBS syndromes indicates the necessity to provide them with appropriate diagnosis and treatment of these abnormalities.

Identifying the alpha-glucosidase inhibitory potential of dietary phytochemicals against diabetes mellitus type 2 via molecular interactions and dynamics simulation.

The research aims to identify the inhibitory potential of natural dietary phytochemicals against non-insulinotropic target protein alpha-glucosidase and its possible implications to diabetes mellitus type 2. A data set of sixteen plant-derived dietary molecules viz., 4,5-dimethyl-3-hydroxy-2(5H)-furanone, apigenin, bromelain, caffeic acid, cholecalciferol, dihydrokaempferol 7-o-glucopyranoside, galactomannan, genkwanin, isoimperatorin, luteolin, luteolin 7-o-glucoside, neohesperidin, oleanoic acid, pelargonidin-3-rutinoside, quercetin, and quinic acid were taken to accomplish molecular docking succeeded by their comparison with known inhibitors including acarbose, miglitol, voglibose, emiglitate, and 1-deoxynojirimycin. Among all phyto-compounds, bromelain (ΔG -9.54 kcalmol), cholecalciferol (-8.47 kcalmol), luteolin (-9.02 kcalmol), and neohesperidin (-8.53 kcalmol) demonstrated better binding interactions with alpha-glucosidase in comparison to the best-known inhibitor, acarbose (ΔG -7.93 kcalmol). Molecular dynamics simulation of 10 ns duration, CYP450 site of metabolism identification, and prediction of activity spectra for substances depicted the bromelain as the most stable inhibitor compared to luteolin and acarbose. Findings of molecular interactions, molecular dynamics study, metabolism, and biological activity prediction proved bromelain as a potential alpha-glucosidase inhibitor. Thus, bromelain might be helpful as an insulin-independent therapeutic molecule towards controlling and managing diabetes mellitus type 2.

Effects of endoplasmic reticulum stress, liver function, insulin resistance and vascular endothelial function in patients with nonalcoholic fatty liver disease.

It is aimed to compare whether there are differences in endoplasmic reticulum stress, liver function, insulin resistance, and vascular endothelial function in patients with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2DM). Forty patients with NAFLD, 38 patients with NAFLD combined with T2DM, and 30 patients with normal liver tissue were selected. They were set as Group A, Group B and Group C respectively. The expression level of glucose-regulated protein 94 (GRP94) and biochemical indicators such as alanine aminotransferase (ALT), free fatty acids (FFA), triglycerides (TG), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), fasting blood glucose (FBG), and fasting insulin (FINS) were measured. Also, the calculation of the homeostatic model assessment for insulin resistance (HOMA-IR) index was performed. The reactive hyperemia index (RHI) was detected to evaluate the vascular endothelial function of patients. The comparison between groups and multi-factor analysis of the influencing factors of RHI was conducted. Compared with Group C, the expressions in Group A and Group B were distinctly enhanced (P <0.05). Also, the expression of GRP94 protein in Group B was distinctly higher than that in Group A (P <0.05). The average optical density values of Groups A, B, and C were 0.327 ± 0.007, 0.350 ± 0.009, and 0.299 ± 0.006, respectively. A comparison between the three groups was performed. The differences had statistical significance (P <0.05). The differences in the TG, ALT, AST, GGT, FINS and HOMA-IR between Group A and Group B had statistical significance (P <0.05). The RHI values of Groups A, B, and C were 1.59 ± 0.23, 1.79 ± 0.32, and 2.05 ± 0.47, respectively. A comparison between the three groups was performed. The differences had statistical significance (P <0.05). FFA, ALT and FBG in patients with NAFLD are risk factors for endothelial dysfunction (P <0.05). The liver damage caused by NAFLD may be related to the expression of GRP94. FFA, ALT and FBG are risk factors for endothelial dysfunction in NAFLD patients.

Atherogenic index of plasma is an independent predictor of metabolic-associated fatty liver disease in patients with type 2 diabetes.

Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease, is the leading cause of liver disease that can ultimately lead to cirrhosis. Identifying a screening marker for early diagnosis of MAFLD in patients with type 2 diabetes (T2D) can reduce the risk of morbidity and mortality. This study investigated the association between the atherogenic index of plasma (AIP) and MAFLD in patients with T2D. A retrospective case-control study was conducted and medical records of patients with T2D were assessed. The baseline characteristics, anthropometric indices, laboratory measurements including liver functions tests, fasting blood sugar, HbA1C, lipid profile were documented. Out of 2547 patients with T2D, 824 (32.4%) had MAFLD. The multivariate logistic regression analysis showed a significant difference in female-to-male ratio (1.11 vs. 1.33, OR 0.347, P-value < 0.001), ALT (42.5 ± 28.1 vs. 22.4 ± 11.1, OR 1.057, P-value < 0.001), and AIP (0.6 ± 0.3 vs. 0.5 ± 0.3, OR 5.057, P-value < 0.001) between MAFLD and non-MAFLD groups, respectively. According to the AIP quartile, the prevalence of MAFLD increased significantly in patients with higher AIP quartiles (P-value < 0.001). Also, we found a cut-off of 0.54 for AIP in predicting MAFLD in patients with T2D (sensitivity 57.8%, specificity 54.4%). In this study, we found that AIP is a good and independent predictor for MAFLD in patients with T2D which could help physicians in early diagnosis and follow-up of patients with T2D.

Geriatric nutritional risk index is associated with retinopathy in patients with type 2 diabetes.

The geriatric nutritional risk index (GNRI) is a nutrition-related risk assessment tool and has been used in various clinical settings. The relationship between body mass index (BMI) and the associated risk of diabetic retinopathy (DR) remains inconclusive. We aimed to evaluate the association between GNRI and DR in patients with type 2 diabetes. We included a total of 1359 patients with type 2 diabetes who followed up in our diabetes clinic and underwent fundus photographic examinations from August 2006 to February 2014. DR was assessed by retinal ophthalmologists using comprehensive ophthalmologic examinations. Patients were divided into tertiles according to their GNRI category. Patients in a lower GNRI tertile tended to have a higher proportion of nonproliferative DR (NPDR) and proliferative DR (PDR) compared with those in the other tertiles. The risk of PDR was higher in patients included in GNRI tertile 1 (Odds ratio (OR) 2.252, 95% Confidence Interval (CI) 1.080-4.823, P 0.033) and GNRI tertile 2 (OR 2.602, 95% CI 1.323-5.336, P 0.007) compared with those in GNRI tertile 3. In patients with lower GNRIs, the prevalence of DR was higher than in those with higher GNRIs. When GNRI was compared with BMI using the area under the curve, overall accuracy was high in GNRI. The risk of PDR was high in patients with low GNRI and there is an inverse association between GNRI scores and prevalence of DR. GNRI might be a useful tool to predict DR in patients with type 2 diabetes.

Efficacy and safety of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy for the treatment of Chinese T2D patients with obesity.

Bariatric surgery is the most effective treatment for obese T2D. As one of the most effective bariatric surgeries, SADI-S was recently introduced in China, and there is limited evidence of its efficacy and safety in the treatment of obese T2D. The aim of this study is to investigate the safety and efficacy of SADI-S in the treatment of obese T2D in China. The clinical data of 32 obese T2D patients who underwent SADI-S was included in this study. Changes in weight-related indicators, diabetes-related indicators, and patient nutritional outcomes were analyzed. SADI-S was conducted successfully in all of the 32 cases without conversion to laparotomy or death. The incidence of surgical complications was 15.6% (532). The major complication rate was 6.3% (232). At 1 year after surgery, the BMI (kgm The SADI-S has excellent curative effect in the treatment of Chinese obese T2D, but the operation is challenging and the complication rate is high. Its long-term efficacy and safety require further study.

Real-life effects of adding weekly subcutaneous semaglutide to insulin for the treatment of type 2 diabetes mellitus.

This work aims to determine the real-life anthropometric and analytical benefits of adding subcutaneous semaglutide to previous insulin treatment in patients with type 2 diabetes. This is a descriptive, retrospective, open-label study describing the clinical and anthropometric characteristics of 117 patients diagnosed with type 2 diabetes followed-up on in the Endocrinology and Nutrition outpatient clinic of the Hospital Universitario Central de Asturias for 53 weeks after starting treatment with subcutaneous semaglutide (October-December 2019). All patients were on previous insulin treatment with or without oral antidiabetics. Of the 117 initial patients, 17 did not complete the study due to adverse effects (nausea, vomiting), the physicians decision, or loss to follow-up. Twelve months (week 53) after starting semaglutide, there was a decrease in HbA1c of 0.74% (95% CI 0.59-1.14, p < 0.05) as well as 3.61 kg of weight loss (95% CI 2.30-4.92, p < 0.05) and a decline in total insulin of 15.88 IU (95% CI 10.98-20.74, p < 0.05) from baseline figures. In patients without prior GLP-1 receptor analogs (GLP-1ra), the effect in terms of a reduction in HbA1c, weight, and the total insulin dose was statistically significant. However, in patients pre-treated with GLP-1ra only had improvements in terms of weight loss. No serious adverse events were observed. The addition of subcutaneous semaglutide to prior insulin treatment with or without oral antidiabetics safely led to a decrease in HbA1c, weight, and the insulin dose. This effect is greater in GLP-1ra naive patients.

Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes - A systematic review and meta-analysis.

The effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders. We conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomesadverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis. GLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05-1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00-1.43), using placebo as a comparator (1.22, 1.05-1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99-1.42) or with subjects enrolled from multiple countries (1.2, 0.99-1.46), the association appeared to be evident but did not reach statistical significance. GLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.

Sodium-glucose cotransporter 2 inhibitor-associated severe epididymo-orchitis.

A man in his late 50s, with uncontrolled type 2 diabetes mellitus (T2DM) and morbid obesity, presented to the hospital with complicated epididymo-orchitis. The onset of symptoms (scrotal pain, erythema and swelling) occurred after the use of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for 2 months. His baseline antidiabetic medications were insulin, glipizide and metformin. Initially, he had failed treatment of epididymo-orchitis with oral levofloxacin for 3 weeks, followed by 2 weeks of doxycycline therapy. At the presentation to the hospital, an ultrasound of the scrotum revealed scrotal and right testicular abscess. The patient underwent right inguinal orchiectomy. Postoperatively, pus culture was positive for

SGLT2i in heart failure can their benefits be expanded across the entire spectrum of ejection fraction

The publication of the EMPEROR-Preserved trial and data on the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with ejection fraction (EF)> 40% represent a significant step forward in the treatment of HF with preserved EF. Given these results, in February 2022 the US Food and Drug Administration approved the use of empaglifozin in adults with HF with reduced or preserved EF. However, more detailed analysis of the EMPEROR-Preserved trial led to doubts about the effect of empagliflozin in patients with an EF of> 60% this patient group is widely heterogeneous and, probably, a single phenotype cannot be considered in treatment goals or the clinical approach. Moreover, EF occurs on a continuum and classifications of HF according to arbitrary cut-points in EF do not appear consistent with recent evidence, which points to a gradual shift and considerable overlap in underlying mechanisms, phenotypes and treatment response over the spectrum of EF. Enhanced knowledge of pathophysiological mechanisms is essential to establish new therapeutic targets, interpret the results of clinical trials, and develop targeted and effective therapies.

Biopolymeric composite hydrogel loaded with silver NPs and epigallocatechin gallate (EGCG) effectively manages ROS for rapid wound healing in type II diabetic wounds.

Delayed wound healing in patients having type-II diabetes mellitus (T2DM) often results in a high rate of amputation. We report an innovative Guar Gum-based macroporous hydrogel (HG) infused with an antibacterial agent (Ag NPs), and antioxidant, epigallocatechin gallate (EGCG) to address rapid wound healing and interestingly could inhibit the associated pathophysical bone infection in a high-fat-diet-induced T2DM C57BL6 mice model. The HG-Ag-EGCG elicits scar-free wound healing in subcutaneous wounds and histopathological evidence confirmed HG-Ag-EGCG hydrogel patch elicits better wound healing through enhanced cell proliferation, mature connecting tissue fiber formation, minimum void spaces formation, and better re-epithelialization when compared with a market available hydrogel patch material (Luofucon®). Supportive of the in vivo outcomes, in vitro experiments delineated better-wound closure due to improved management of ROS by the HG-Ag-EGCG. Additionally, a favorable non-toxicity outcome assessed through both in vitro and in vivo conditions confirmed its potential applicability in clinical wound care management.

Monosodium glutamate in a type 2 diabetes context A large scoping review.

This scoping review aimed to map and elaborate the heterogenous and inconclusive body of evidence relating monosodium glutamate (MSG) and type 2 diabetes (T2DM). For this reason, multiple health outcomes related to T2DM were included and a systematic search was conducted. Experimental and observational trials between 1995 and January 2021 were collected. The tests were highly heterogenous in their samples, doses, route of exposures, durations, diets and conclusions. There was a pattern of negative effects of MSG at oral doses ≥2,000 mgkg of body weight, and by gavage or injection at any given dose. Evidence was lacking in many areas and most of the evidence relied on short term tests. Further research should focus on standardizing and justifying methodologies, conducting long term studies and toxicokinetic tests, and avoiding bias. Focusing on the gaps highlighted and investigating mechanisms of action of MSG is crucial. Evidence-based toxicology is encouraged.

A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women.

Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C160, C241 and C240 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C160C220C241C240 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C160 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.

Protein Biomarkers and Cardiovascular Outcomes in People With Type 2 Diabetes and Acute Coronary Syndrome The ELIXA Biomarker Study.

To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death. Biobanked serum from 4,957 ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial participants was analyzed. Forward-selection Cox models identified independent protein risk factors for major adverse cardiovascular events (MACE) and death that were compared with a previously validated biomarker panel. NT-proBNP and osteoprotegerin predicted both outcomes. In addition, trefoil factor 3 predicted MACE, and angiopoietin-2 predicted death (C 0.70 and 0.79, respectively, compared with 0.63 and 0.66 for clinical variables alone). These proteins had all previously been identified and validated. Notably, C statistics for just NT-proBNP plus clinical risk factors were 0.69 and 0.78 for MACE and death, respectively. NT-proBNP and other proteins independently predict cardiovascular outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNPs prognostic value.

Metabolic, Intestinal, and Cardiovascular Effects of Sotagliflozin Compared With Empagliflozin in Patients With Type 2 Diabetes A Randomized, Double-Blind Study.

Inhibiting sodium-glucose cotransporters (SGLTs) improves glycemic and cardiovascular outcomes in patients with type 2 diabetes (T2D). We investigated the differential impact of selective SGLT2 inhibition and dual inhibition of SGLT1 and SGLT2 on multiple parameters. Using a double-blind, parallel-group design, we randomized 40 patients with T2D and hypertension to receive the dual SGLT1 and SGLT2 inhibitor sotagliflozin 400 mg or the selective SGLT2 inhibitor empagliflozin 25 mg, with preexisting antihypertensive treatment, for 8 weeks. In an in-house testing site, mixed-meal tolerance tests (MMTTs) and other laboratory and clinical evaluations were used to study metabolic, intestinal, cardiovascular, and urinary parameters over 24 h. Changes from baseline in glycemic and blood pressure control intestinal, urine, and metabolic parameters and cardiovascular biomarkers were generally similar with sotagliflozin and empagliflozin. During the breakfast MMTT, sotagliflozin significantly reduced incremental area under the curve (AUC) values for postprandial glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) and significantly increased incremental AUCs for postprandial glucagon-like peptide 1 (GLP-1) relative to empagliflozin, consistent with sotagliflozin-mediated inhibition of intestinal SGLT1. These changes waned during lunch and dinner MMTTs. Both treatments significantly lowered GIP incremental AUCs relative to baseline over the 14 h MMTT interval the most vigorous effect was seen with sotagliflozin soon after start of the first meal of the day. No serious or severe adverse events were observed. Changes from baseline in glycemic and blood pressure control, cardiovascular biomarkers, and other parameters were comparable between sotagliflozin and empagliflozin. However, sotagliflozin but not empagliflozin inhibited intestinal SGLT1 after breakfast as shown by larger changes in postprandial glucose, insulin, GIP, and GLP-1 AUCs, particularly after breakfast. Additional study is warranted to assess the clinical relevance of transient SGLT1 inhibition and differences in incretin responses (NCT03462069).

Effect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue A meta-analysis.

Glucagon-like peptide-1 (GLP-1) analogues reduce body fat and cardiovascular events in patients with type 2 diabetes. Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and coronary events in type 2 diabetes. A systematic review and meta-analysis were performed from Glucagon-like peptide-1 analogues therapy on type 2 diabetes patients, reporting data from changes in EAT, after searching the PubMedMEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. It has been found a limited number of studies, a total of 4 studies (n 160 patients with GLP-1 analogues therapy) were included in the final analysis. Pooled analysis revealed that GLP-1 analogues reduce EAT (MD 1.83 mm -2.50 -1.10 P < 0.01). Compared with the patients before the treatment, the patients after the treatment had a smaller HbA1c (MD -1.10%-1.80 -0.30 p 0.0143) and body mass index was reduced (MD -2.20 kgm This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with Glucagon-like peptide-1 analogues.

Carotid intima media as predictor of liver fibrosis in type 2 diabetes mellitus with NAFLD.

Non Alcoholic Fatty Liver Disease (NAFLD) is common in type 2 Diabetes Mellitus (DM) that might progress to advance liver fibrosis. Early recognition of liver fibrosis may have clinical implication. Non invasive assessment tool for severity of liver fibrosis in NAFLD is expensive fibroscan. An alternate method of diagnosis will be very useful innovation. We aimed to evaluate Carotid Intima Media Thickness (CIMT) and its association with severity of liver fibrosis in patients with type 2 DM and NAFLD. Treatment naïve patients with type 2 DM were enrolled. Measurement of CIMT, hepatic ultrasound and fibroscan were done. Liver function tests included hepatic transaminases. The data obtained was subjected to statistical analysis using IBM SPSS version 20.0 software. Prevalence of NAFLD was 76% including 12% with moderate to advance liver fibrosis in patients with type 2 DM. CIMT was significantly higher in patients with NAFLD than with normal liver. CIMT positively correlated with severity of liver fibrosis measured by fibroscan. ROC curve analysis showed right CIMT value of 0.575 mm predicting liver fibrosis with sensitivity of 91.7% and specificity of 78.9%. Three fourth of patients with type 2 DM had NAFLD but small proportion had moderate to advance liver fibrosis. CIMT increased more in patients with NAFLD than with normal liver in T2DM. CIMT value of 0.575 mm has a good sensitivity to predict liver fibrosis and therefore, it can be a reliable marker of severity of Non Alcoholic Steato Hepatitis (NASH) in diabetes with NAFLD.

Appraising the causal role of smoking in multiple diseases A systematic review and meta-analysis of Mendelian randomization studies.

The causal association between cigarette smoking and several diseases remains equivocal. The purpose of this study was to appraise the causal role of smoking in a wide range of diseases by summarizing the evidence from Mendelian randomization (MR) studies. MR studies on genetic liability to smoking initiation or lifetime smoking (composite of smoking initiation, heaviness, duration, and cessation) in relation to circulatory system, digestive system, nervous system, musculoskeletal system, endocrine, metabolic, and eye diseases, and neoplasms published until February 15, 2022, were identified in PubMed. De novo MR analyses were performed using summary statistics data from genome-wide association studies. Meta-analysis was applied to combine study-specific estimates. Meta-analyses of findings of 29 published MR studies and 123 de novo MR analyses of 57 distinct primary outcomes showed that genetic liability to smoking (smoking initiation or lifetime smoking) was associated with increased risk of 13 circulatory system diseases, several digestive system diseases (including diverticular, gallstone, gastroesophageal reflux, and Crohns disease, acute pancreatitis, and periodontitis), epilepsy, certain musculoskeletal system diseases (including fracture, osteoarthritis, and rheumatoid arthritis), endocrine (polycystic ovary syndrome), metabolic (type 2 diabetes) and eye diseases (including age-related macular degeneration and senile cataract) as well as cancers of the lung, head and neck, esophagus, pancreas, bladder, kidney, cervix, and ovaries, and myeloid leukemia. Smoking liability was associated with decreased risk of Parkinsons disease and prostate cancer. This study found robust evidence that cigarette smoking causes a wide range of diseases. This work was supported by research grants from the Swedish Cancer Society (Cancerfonden), the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), and the Swedish Research Council (Vetenskapsrådet, 2019-00977). Stephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623Z16Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.

Systematic review of the impact of genistein on diabetes-related outcomes.

Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death worldwide, especially for individuals with diabetes. Although medications exist to treat symptoms of diabetes, lack of availability and high costs may deter their use by individuals with low incomes as well as those in low-income nations. Therefore, this systematic review was performed to determine whether genistein, a phytoestrogen found in soy products, could provide therapeutic benefits for individuals with diabetes. We searched PubMed and SCOPUS using the terms genistein, diabetes, and glucose and identified 33 peer-reviewed articles that met our inclusion criteria. In general, preclinical studies demonstrated that genistein decreases body weight and circulating glucose and triglycerides concentrations, whereas increasing insulin levels and insulin sensitivity. Genistein also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies utilizing genistein generally reported no significant relationship between genistein and body mass, circulating glucose, glycated hemoglobin (A1C) concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity and serum triglyceride concentrations and delayed the onset of type 2 diabetes. In summary, preclinical and clinical studies suggest that genistein may help delay the onset of type 2 diabetes and improve several symptoms associated with the disease. Although additional research is required to confirm these findings, the results highlighted in this review provide some evidence that genistein may offer a natural approach to mitigating some of the complications associated with diabetes.

Psychometric evaluation of three-factor eating questionnaire -R18 in aging Finnish men with increased risk for type 2 diabetes.

Deeper comprehension of eating-related behaviour (how and why people eat) can reveal new aspects to support health and prevent type 2 diabetes (T2D). However, such research is largely missing in aging men. The aim was to investigate suitability of the Three-Factor Eating Questionnaire-R18 (TFEQ-R18) in Finnish aging men which is widely used to examine factors cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). Study population consisted of 420 men aged 50-75, who completed the TFEQ-R18 at the baseline of the T2D-GENE lifestyle intervention study. Inclusion criteria were impaired fasting glucose (IFG) and body mass index ≥25 kgm The items loaded to the three factors (CR, UE, EE) as in previous studies, except two items at CR factor and one at UE factor, which were therefore omitted. UE was also discovered split into two sub factors (named as craving and loss-of-control), UE being a higher-order (h) factor. The resultant revised version was named as Three-Factor Eating Questionnaire Revised to 15-items with higher-order factor (TFEQ-R15h). The original 18-item version of the TFEQ was not optimal in the population consisting of Finnish aging men with elevated T2D risk. A modified 15-item version of the TFEQ could be used to describe EB in this population instead.

Preclinical Studies of Natural Products Targeting the Gut Microbiota Beneficial Effects on Diabetes.

Diabetes mellitus (DM) is a serious metabolic disease characterized by persistent hyperglycemia, with a continuously increasing morbidity and mortality. Although traditional treatments including insulin and oral hypoglycemic drugs maintain blood glucose levels within the normal range to a certain extent, there is an urgent need to develop new drugs that can effectively improve glucose metabolism and diabetes-related complications. Notably, accumulated evidence implicates that the gut microbiota is unbalanced in DM individuals and is involved in the physiological and pathological processes of this metabolic disease. In this review, we introduce the molecular mechanisms by which the gut microbiota contributes to the development of DM. Furthermore, we summarize the preclinical studies of bioactive natural products that exert antidiabetic effects by modulating the gut microbiota, aiming to expand the novel therapeutic strategies for DM prevention and management.

Benefits of telematic monitoring for weight loss in overweight and obese patients in times of confinement.

Introduction the pandemic originated by SARS-Cov-2 in 2019 led to eating habits and physical exercise changes due to home confinement measures. The follow-up of patients in treatment for weight loss through telematic consultation could be a useful tool to prevent treatment failure. Objective to describe the evolution of anthropometric parameters of patients under follow-up for weight loss through telematic consultation. Methods a two-stage prospective study (before and after confinement) with a telematic intervention in adult patients under regular follow-up for overweight and obesity. Demographic variables and body composition parameters were analyzed by bioimpendance. In addition, the differences in the presence of drug treatment with GLP-1 hormone (liraglutide or semaglutide) adjuvants were also analyzed. The variables were studied using Wilcoxons test, Mann-Whitney U-test, and Spearmans correlation. Significance was considered for p ≤ 0.05. Results a total of 97 patients were included, before confinement 42.3 % were overweight (BMI < 30 kgm2), 36.1 % were obese grade I (BMI 30-34.9 kgm2), 16.4 % were obese grade II (BMI 35-39.9 kgm2), and 5.2 % had BMI > 40 kgm2. In all, 30.9 % had prediabetes and 9.3 % had type-2 diabetes. Between both consultations, 81.4 % of patients lost 4.2 ± 3.4 % of their weight, with a significant mean decrease in fat mass of 3.16 ± 4.4 kg. The group on pharmacological treatment with GLP-1 hormone analogs presented a significantly higher average fat loss without significant loss of skeletal muscle mass. Conclusions telematic monitoring seems to be a useful tool to prevent weight gain in patients with restricted mobility. A telematic intervention that contains dietary advice and exercise, as a reinforcement to hypocaloric diet, helps to achieve weight loss with a predominant fat component. The presence of drug treatment with GLP-1 hormone analogues appears to significantly help maintain skeletal muscle mass during weight loss. Introducción la pandemia originada en 2019 por el SARS-CoV-2 supuso un cambio en los hábitos de alimentación y ejercicio físico por causa de las medidas de confinamiento domiciliario. El seguimiento de pacientes en tratamiento de pérdida de peso mediante una consulta telemática podría ser una herramienta útil para prevenir el fracaso terapéutico. Objetivo describir la evolución de los parámetros antropométricos de pacientes en seguimiento para pérdida de peso mediante una consulta telemática. Métodos estudio prospectivo en 2 tiempos (antes y después del confinamiento) de una intervención telemática sobre pacientes adultos en seguimiento habitual por sobrepeso y obesidad. Se analizaron las variables demográficas y los parámetros de composición corporal mediante bioimpendancia. Además se analizaron las diferencias en cuanto a presencia de tratamiento farmacológico adyuvante del tipo de los análogos de la hormona GLP1 (liraglutida o semaglutida). Las variables se estudiaron mediante la prueba de Wilcoxon, la U de Mann-Whitney y la correlación de Spearman. Se consideró la significación si p ≤ 0,05. Resultados se incluyeron 97 pacientes. Antes del confinamiento, el 42,3 % presentaban sobrepeso (IMC < 30 kgm2), el 36,1 % tenían obesidad de grado I (IMC 30-34,9 kgm2), el 16,4 % la tenían de grado II (IMC 35-39,9 kgm2) y el 5,2 % tenían un IMC > 40 kgm2. El 30,9 % presentaban prediabetes y el 9,3 % tenían diabetes de tipo 2. Entre ambas visitas presenciales, el 81,4 % de los pacientes perdieron un 4,2 ± 3,4 % del peso, con una disminución media significativa de la masa grasa de 3,16 ± 4,4 kg. El grupo en tratamiento farmacológico con análogos de la hormona GLP-1 presentó una pérdida de masa grasa media significativamente superior sin pérdida de masa muscular esquelética significativa. Conclusiones el seguimiento telemático parece una herramienta útil para prevenir la ganancia de peso en los pacientes con restricción de la movilidad. Una intervención telemática que contenga consejo dietético y ejercicio como refuerzo de la dieta hipocalórica ayuda a conseguir perder peso, predominando el componente graso. La presencia de un tratamiento farmacológico con análogos de la hormona GLP-1 parece ayudar significativamente al mantenimiento de la masa muscular esquelética durante la pérdida de peso.

Effect of 52 % low-sodium salt applied to CM-DASH Diet on atherosclerotic cardiovascular disease risks in patients with hypertension and type-2 diabetes.

Introduction hypertension and diabetes are chronic disorders associated with an increased risk of cardiovascular disease. Objectives to evaluate the effect of 52 % low-sodium salt applied to the Chinese-modified DASH (CM-DASH) diet on risk of atherosclerotic cardiovascular disease (ASCVD) in patients with hypertension and type-2 diabetes. Methods the low-sodium salt group (LSSG) took 5 gday of 52 % low-sodium salt plus CM-DASH diet for 8 weeks, while the normal-sodium salt group (NSSG) took the same dose of normal-sodium salt plus CM-DASH diet for 8 weeks. Blood tests, 24-hour urine tests, anthropometric measurements, and 10-year risk of ASCVD prediction were assessed. Results compared with baseline, both LSSG and NSSG showed a significant reduction in 10-year risk of ASCVD, but we did not find any statistically significant differences in 10-year risk of ASCVD between LSSG and NSSG. Conclusions our study shows that salt limits and DASH diets reduce the risk of cardiovascular disease whereas low-sodium salt containing 52 % sodium chloride did not significantly lower the risk of cardiovascular disease when compared to regular salt. Due to the limitations of the research, additional studies will be necessary to confirm our findings. Introducción la hipertensión y la diabetes son trastornos crónicos asociados a un mayor riesgo de enfermedad cardiovascular. Objetivos evaluar el efecto de la sal baja en sodio (52 %) aplicada a la dieta DASH modificada en China (CM-DASH) sobre los riesgos de enfermedad cardiovascular aterosclerótica (ECA) en pacientes con hipertensión arterial y diabetes de tipo 2. Métodos el grupo de sal baja en sodio (LSSG) tomó 5 gdía de sal baja en sodio al 52 % más dieta CM-DASH durante 8 semanas, mientras que el grupo de sal normal en sodio (NSSG) tomó la misma dosis de sal normal en sodio más dieta CM-DASH durante 8 semanas. Se evaluaron los análisis de sangre, los análisis de orina de 24 horas, las mediciones antropométricas y los riesgos de predicción de ECVA a 10 años. Resultados en comparación con el valor basal, tanto el LSSG como el NSSG mostraron una reducción significativa de los riesgos a 10 años de ECVA, mientras que no se encontraron diferencias estadísticamente significativas en los riesgos a 10 años de ECVA entre el LSSG y el NSSG. Conclusiones nuestro estudio muestra que los límites de sal y las dietas DASH reducen el riesgo de enfermedad cardiovascular mientras que la sal baja en sodio con un 52 % de cloruro sódico no redujo significativamente el riesgo de enfermedad cardiovascular en comparación con la sal normal. Debido a las limitaciones de la investigación, serán necesarios estudios adicionales para confirmar nuestros hallazgos.

Younger Age and Albuminuria are Associated with Proliferative Diabetic Retinopathy and Diabetic Macular Edema in the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study.

Evogliptin for the treatment option for type 2 diabetes an update of the literature.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have been the most widely used for type 2 diabetes (T2D) available worldwide since 2006. DPP-4 inhibitors exert their effects by inhibiting dipeptidyl peptidase-4 to increase the concentration of endogenous incretin hormones (incretin hormone analogues and incretin potentiators) and promote insulin secretion, thereby acting as a glucose regulator. Evogliptin is a new member of the DPP-4 inhibitor family with high selectivity and low risk of hypoglycemia, and extensive clinical data has been accumulated in its treatment of T2D since its introduction in October 2015. This review summarized the recently reported studies associated with the pharmacokinetics, pharmacodynamics, safety and tolerability, and clinical application of evogliptin for managing T2D. We searched the MEDLINE and PubMed databases with the titles evogliptin to identify all the information. The abstracts and posters of the annual meetings of ADA and EASD and clinicalTrials.gov. have been searched up to now. Evogliptin is a potent, orally effective, and highly selective DPP-4 inhibitor that is not only indicated for the treatment of T2D but may also be beneficial to arterial inflammation and atherosclerosis, with good safety and tolerance.

The glucose tolerance test in mice Sex, drugs and protocol.

To establish the impact of sex, dosing route, fasting duration and acute habituation stress on glucose tolerance test (GTT) measurements used in the preclinical evaluation of potential glucose-modulating therapeutics. Adult male and female C57Bl6J mice, implanted with HD-XG glucose telemetry devices, were fasted for 16 hours or 6 hours following acute habituation stress due to whole cage change, cage change with retention of used bedding or no cage change prior to intraperitoneal (IP) GTTs. To evaluate protocol refinement and sex on the ability of the GTT to detect drug effects, we administered 250 mgkg oral metformin or 10 nmolkg IP exendin-4 using optimized protocols. Female mice were less sensitive to human intervention when initiating fasting. Following a 6-hour fast, retention of bedding whilst changing the cage base promotes quicker stabilization of basal blood glucose in both sexes. Prolonged fasting for 16 hours resulted in an exaggerated GTT response but induced pronounced basal hypoglycaemia. Following GTT protocol optimization the effect of exendin-4 and metformin was equivalent in both sexes, with females showing a more modest but more reproducible GTT response. Variations in GTT protocol have profound effects on glucose homeostasis. Protocol refinement andor the use of females still allows for detection of drug effects, providing evidence that more severe phenotypes are not an essential prerequisite when characterizingvalidating new drugs.

Measuring the Awareness of Chronic Kidney Disease (CKD) with Environmental Evaluation among Adult Diabetic Patients in Hail Region, Saudi Arabia.

Chronic kidney disease (CKD) is one of the main chronic complications of T2DM that happens among T2DM patients who have uncontrolled glucose. Because CKD is considered a silent disease, the diagnosis is usually made at late stages when there will be few chances to prevent the adverse outcome. The goal of this study was to assess adult diabetic patients awareness of developing chronic kidney disease at the community level in Hail region, Saudi Arabia, in 2022. 400 DM patients responded to our survey (51% females vs 49% males). Patients who were diagnosed with type 2 diabetes were 23.8% and 40.5% had a diabetes duration of 5-15 years. Nearly half (46.8%) were considered as a poor level of awareness, 29.3% had a moderate, and 24% had a good awareness level. Factors associated with an increased level of awareness were being a bachelors degree, being unmarried, being a student, and having a doctor as a source of CKD information. There was a deficiency in the level of awareness among the diabetic patients in our region. Patients who were single with better education and who were well informed by the doctors about CKD information tend to be more aware of CKD as compared to other DM patients. Further research is warranted in order to establish the awareness level of DM patients regarding CKD and its complications.

Extending drug release from implants via transcutaneous refilling with solid therapeutics.

Long-acting (LA) implantable drug delivery systems (IDDS) offer an effective approach for the management or prevention of chronic conditions by sustained parenteral therapeutic administration. LA IDDS can and improve adherence to treatment regimens by minimizing dosing frequency. However, their clinical deployment is challenged by factors such as poor drug loading capacity, which limit their lifespan and require repeated surgical replacement for continued therapy. To address these challenges, and by leveraging previous work on nanofluidic systems, a reservoir-based IDDS that enables transcutaneous refilling of solid drug formulations through minimally invasive needle injection is presented. With thousand-fold higher drug loading efficiency, the implant affords minimal volume and aspect ratio suitable for discrete subcutaneous deployment. Key parameters for clinical acceptability, namely implant safety, access port robustness, and refilling method were systematically evaluated. The implant and refilling procedure are studied in rats and nonhuman primates with therapeutics used clinically for type 2 diabetes and human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). The ability to extend drug release and maintain equivalent pharmacokinetics (PK) profiles pre- and post-drug refilling is demonstrated. This technology presents a clinically viable LA approach to prolong drug release for lifelong prevention or management of chronic conditions.

Views on high-fat diet linked insulin resistance.

Insulin resistance is linked to impaired cell metabolism and survival in the peripheral tissues, as well as increased oxidative stress and activated inflammatory responses. Chronic High fat diet insulin resistant to exposure results in liver damage, impaired glucose homeostasis, hyperinsulinemia, late pancreatic-cell failure to generate insulin due to cell exhaustion, and subsequent hyperglycaemia, all of which are hallmarks of Type 2 Diabetes Mellitus (T2DM). Therefore, it is of intrest to document a short review on the impact of a high-fat diet with insulin resistance.

Patient Work Personas of Type 2 Diabetes-A Data-Driven Approach to Persona Development and Validation.

Many have argued that a one-size-fits-all approach to designing digital health is not optimal and that personalisation is essential to achieve targeted outcomes. Yet, most digital health practitioners struggle to identify which design aspect require personalisation. Personas are commonly used to communicate patient needs in consumer-oriented digital health design, however there is often a lack of reproducible clarity on development process and few attempts to assess their accuracy against the targeted population. In this study, we present a transparent approach to designing and validating personas, as well as identifying aspects of patient work, defined as the combined total of work tasks required to manage ones health and the contextual factors influencing such tasks, that are sensitive to an individuals context and may require personalisation. A data-driven approach was used to develop and validate personas for people with Type 2 diabetes mellitus (T2DM), focusing on patient work. Eight different personas of T2DM patient work were constructed based physical activity, dietary control and contextual influences of 26 elderly Australian participants (median age 72 years) Both the original participants and the independent online cohort reported the personas to be accurate representations of their patient work routines. For the independent online cohort, 74% (97131) indicated personas stratified to their levels of exercise and diet control were similar to their patient work routines. Findings from both cohorts highlight aspects that may require personalisation include Personas made for a specific purpose can be very accurate if developed from real-life data. Our personas retained their accuracy even when tested against an independent cohort, demonstrating their generalisability. Our data-driven approach clarified the often non-transparent process of persona development and validation, suggesting it is possible to systematically identify whether persona components are accurate or. and which aspects require more personalisation and tailoring.

Potential effect of real-world junk food and sugar-sweetened beverage taxes on population health, health system costs and greenhouse gas emissions in New Zealand a modelling study.

Poor diet is a major risk factor for excess weight gain and obesity-related diseases, including cardiovascular diseases, type 2 diabetes mellitus, osteoarthritis and several cancers. This paper aims to assess the potential impacts of real-world food and beverage taxes on change in dietary risk factors, health gains (in quality-adjusted life years (QALYs)), health system costs and greenhouse gas (GHG) emissions as if they had all been implemented in New Zealand (NZ). Ten taxes or tax packages were modelled. A proportional multistate life table model was used to predict resultant QALYs and costs over the remaining lifespan of the NZ population alive in 2011, as well as GHG emissions. QALYs ranged from 12.5 (95% uncertainty interval (UI) 10.2 to 15.0 3% discount rate) per 1000 population for the import tax on sugar-sweetened beverages (SSB) in Palau to 143 (95% UI 118 to 171) per 1000 population for the excise duties on saturated fat, chocolate and sweets in Denmark, while health expenditure savings ranged from 2011 NZ$245 (95% UI 188 to 310 2020 US$185) per capita to NZ$2770 (95% UI 2140 to 3480 US$2100) per capita, respectively. The modelled taxes resulted in decreases in GHG emissions from baseline diets, ranging from -0.2% for the tax on SSB in Barbados to -2.8% for Denmarks tax package. There is strong evidence for the implementation of food and beverage tax packages in NZ or similar high-income settings.

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK.

To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity. General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases. 325 subjects engaged in the programme and had sufficient data for analysis. Baseline characteristics were age 47.8±12. 8 years body mass index (BMI) 36.1±6.8 kgm Long-term maintenance of weight loss after VLCD was rare in this single centre retrospective study 15 years later. Glucose intolerance developed in 21.4%. Lasting remission of type 2 diabetes or prevention of later glucose intolerance were not achieved. Vascular events were more frequent in those who lost most weight. Risk management during weight regain should be studied in future to assess potential for reduction in adverse cardiovascular outcomes.

Quantitative Ultrasound Assessment of Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is widespread chronic disease of the live in humans with the prevalence of 30% of the United States population. This prospective study enrolled a total of 31 patients with clinical suspicion of NAFLD to receive liver fat measurements by quantitative ultrasound and reference MRI measurements (proton density fat-fraction, PDFF). The following ultrasound (US) parameters based on both raw ultrasound RF (Radio Frequency) data and 2D B-mode images of the liver were analyzed with subsequent correlation with MRI-PDFF hepatorenal index, acoustic attenuation coefficient, Nakagami coefficient parameter, shear wave viscosity, shear wave dispersion and shear wave elasticity. Ultrasound parameters were also correlated with the presence of hypertension and diabetes. The mean (± SD) age and body mass index of the patients were 49.03 (± 12.49) and 30.12 (± 6.15), respectively. Of the aforementioned ultrasound parameters, the hepatorenal index and acoustic attenuation coefficient showed a strong correlation with MRI-PDFF derivations of hepatic steatosis, with Hepatorenal index and acoustic attenuation coefficient correlate well with MRI-PDFF-derived measurements of hepatic steatosis. Quantitative ultrasound is a promising tool for the diagnosis and assessment of patients with NAFLD.

A Comparative Study of the Effect of Two Procedures of Classic Roux-en-Y and Omega Bariatric Surgery on the Control and Management of Diabetes.

Patient management after bariatric surgery is important in controlling patients diabetes and recurrence prevention. This study aimed to meet the medical managements of patients with diabetes 6 months after the bariatric surgery. This cross-sectional study was performed on 77 type 2 diabetes patients candidates for bariatric surgery (Roux-en-Y RYGP and Omega). Postoperative implementation protocol was one-third of insulin for patients taking long-term insulin and the discontinuation of medications for patients of oral antidiabetic agents. Blood glucose (BG) level was checked regularly by the patients at home and the necessary medical management was applied. The weight, BG and HbA1C levels, and use of oral antidiabetic agents and insulin were assessed and recorded before 1, 3, and 6 months after the surgery. BG levels and HbA1C percentage in the 1 The long-term management and support of the patients by the implementation of a standard protocol after surgery are of great significance in obtaining the optimal outcome after bariatric surgery.

Peripheral Cytopenia and Its Associated Factors in Type 2 Diabetes Mellitus Patients, Northwest Ethiopia.

Hematological abnormalities are linked with diabetes mellitus (DM) and play a major role in diabetes-related micro- and macro-vascular complications. Therefore, this study aimed to investigate the magnitude of peripheral cytopenia and associated factors in type 2 diabetes (T2DM) patients. A cross-sectional study was conducted from March to May 2021 at the University of Gondar Comprehensive Specialized Hospital. A total of 357 T2DM participants were selected using a simple random sampling technique. A total of 3 mL of venous blood samples were collected using the vacutainer method for the complete blood count (CBC). A univariate and multivariate regression analysis were used to investigate the association between dependent and independent variables. P-value ˂0.05 was considered statistically significant. The magnitude of cytopenia, bicytopenia, and pancytopenia were 21% (95% CI 17.1, 25.53), 1.1% (95% CI 0.44, 2.85), and 0.56% (95% CI 0.01, 1.12), respectively. Furthermore, the magnitudes of anemia, leucopenia, and thrombocytopenia were 8.7% (95% CI 6.18, 12.06), 10.9% (95% CI 8.09, 14.59), and 5.3% (95% CI 3.43, 8.16), respectively. Being male (AOR 3.23 95% CI 1.43, 7.56), lack of exercise (AOR 2.70 95% CI 1.137, 6.43), and never married (AOR 3.90 95% CI 1.248, 12.18) were all associated with anemia. This study showed that T2DM causes disturbances in the hematological parameters and leads to a mild level of cytopenia. It is, therefore, suggested that hematological abnormalities, especially cytopenia, should be monitored and controlled on a regular basis in T2DM patients for better prognosis and quality of life.

Relevance of NLRP3 Inflammasome-Related Pathways in the Pathology of Diabetic Wound Healing and Possible Therapeutic Targets.

Wound healing is a major secondary complication in type 2 diabetes, which results in significant disability and mortality, imposing a significant clinical and social burden. Sustained activation of the Nod-like receptor protein (NLRP) inflammasome in wounds is responsible for excessive inflammatory responses and aggravates wound damage. The activation of the NLRP3 inflammasome is regulated by a two-step process the priminglicensing (signal 1) step involved in transcription and posttranslation and the protein complex assembly (signal 2) step triggered by danger molecules. This review focuses on the advances made in understanding the pathophysiological mechanisms underlying wound healing in the diabetic microenvironment. Simultaneously, this review summarizes the molecular mechanisms of the main regulatory pathways associated with signal 1 and signal 2, which trigger the NLRP3 inflammasome complex assembly in the development of diabetic wounds (DW). Activation of the NLRP3 inflammasome-related pathway, involving the disturbance in Nrf2 and the NF-

L-GSH Supplementation in Conjunction With Rifampicin Augments the Treatment Response to

Both active tuberculosis (TB) and asymptomatic latent

Cerebral Small Vessel Disease is Associated with Mild Cognitive Impairment in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, but the underlying cerebral small vessel disease (CSVD)-related structural brain correlates are unclear. The aim of this study was to investigate the relationship between various imaging markers of CSVD and mild cognitive impairment (MCI) in patients with T2DM. A total of 228 eligible participants with T2DM who were divided into MCI group and normal cognitive group based on neuropsychological assessment were enrolled in this retrospective study. White matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS) were evaluated based on brain magnetic resonance imaging (MRI). The total CSVD burden score was calculated by combining the above four markers of CSVD. Binary logistic regression analysis was used to evaluate the relationship between different imaging markers of CSVD and MCI in patients with T2DM. Kruskal-Wallis test and Jonckheere-Terpstra test were used to compare mean MoCA scores among individuals with varying CSVD markers. In the multivariate binary logistic regression analyses, moderate or severe total CSVD burden (OR 3.29, 95% CI 1.63-7.38, Different imaging markers of CSVD, particularly total CSVD burden, were associated with an increased risk of MCI and decline in MoCA scores in patients with T2DM. These findings may provide clues for future studies to explore early diagnostic imaging markers of cognitive impairment in relation to T2DM.

Knowledge of the Therapeutic Goals of Diabetes Care among Patients with Type 2 Diabetes at a Tertiary Hospital in Ethiopia.

A comprehensive cardiovascular risk control reduces diabetes-associated complications but achieving the triplet goals (blood glucose, blood pressure (BP), and low-density lipoprotein (LDL-C)) remains a clinical challenge. Patients knowledge of these diabetes therapeutic goals has been shown to improve glycemic control. However, this is not well studied in Ethiopia. A cross-sectional study was conducted from March to June 2020 in Tikur Anbessa Specialized Hospital among randomly selected 419 patients with type 2 diabetes. Data was collected using a pretested, structured questionnaire. A multivariable binary logistic regression was fitted to identify determinants of knowledge. The mean age (±SD) of study participants was 57.4 (±10.8) years and the median duration (IQR) of diabetes was 12 (7, 20) years. A quarter of them achieved fasting glycemic control, a fifth of them attained the A1c goal and only 3% achieved the triple targets. Patients who reported knowing their target goals for BP, fasting blood sugar (FBS), A1C, and LDL-C were 79.5, 77.3, 11.7, and 7.2% respectively. The factors associated with knowledge of the therapeutic goals were longer diabetes duration, increased household income, age, being divorced as compared to married, having no formal education, and primary education. The majority of participants knew their BP and FBS targets while only a minority understood their A1c and LDL-C targets. It highlighted the need for the provision of patient-centered diabetes education to improve knowledge of the therapeutic targets.

Pyogenic Liver Abscess Presenting as an Initial Manifestation of Underlying Hepatocellular Cancer A Case Report in Ethiopia.

An adult patient presented with right abdominal pain and fever to a primary care physician and abdominal ultrasound was performed. With an initial diagnosis of a liver abscess, he was discharged from the hospital after treatment with antibiotics and drainage of the collection. However, the patient had persistent clinical findings on the same site which was later confirmed as Hepatocellular cancer. A 40 years old male patient who was known to have Type 2 Diabetes and Hypertension for 10 years on oral medications referred to the GastroenterologyHepatology unit with right upper quadrant pain, loss of appetite, nausea, vomiting of ingested matter, and significant weight loss. On further inquiry, he had been admitted six months back for similar complaints and was managed with antibiotics and drainage of an abscess collection.The multi-phasic abdominal CT scan and raised alphafetoprotein confirmed Hepatocellular Cancer which initially has presented as a pyogenic liver abscess. Hepatocellular cancer should be suspected and early diagnosis should be made in individuals presenting with a liver abscess and having risk factors for liver cancer.

Gestational Diabetes Mellitus and Energy-Dense Diet What Is the Role of the InsulinIGF Axis

Gestational diabetes mellitus (GDM), is one of the most important pregnancy complications affecting approximately 15% of pregnant women. It is related to several gestational adverse outcomes in the fetus,

Metabolic Stress Impairs Pericyte Response to Optogenetic Stimulation in Pancreatic Islets.

Pancreatic islets are highly vascularized micro-organs ensuring whole body glucose homeostasis. Islet vascular cells play an integral part in sustaining adequate insulin release by beta cells. In particular, recent studies have demonstrated that islet pericytes regulate local blood flow velocity and are required for maintenance of beta cell maturity and function. In addition, increased metabolic demand accompanying obesity alters islet pericyte morphology. Here, we sought to explore the effects of metabolic stress on islet pericyte functional response to stimulation in a mouse model of type 2 diabetes, directly in the pancreas

Ramadan Fasting and Maternal and Fetal Outcomes in Pregnant Women with Diabetes Mellitus Literature Review.

There is an emerging Muslim and diabetic population in the United States and other Western countries and majority of pregnant women and patients with diabetes mellitus choose to fast during Ramadan. Fasting during Ramadan in pregnant women with diabetes may represent a perfect storm of metabolic disturbances including hyperglycemia, hypoglycemia and ketosis. Recent continuous and flash glucose monitoring data suggests increased glycemic variability (fasting hypo- and post-Iftar hyperglycemia) in non-pregnant patients with diabetes during Ramadan. Only five small-scale studies, predominantly focused on women with gestational diabetes mellitus in Muslim-majority nations have explored maternal glycemic outcomes during Ramadan which is associated with lower mean blood glucose levels and higher frequency of fasting hypoglycemia. Data is limited however on important clinical outcomes such as symptomatic and serious hypoglycemia requiring hospitalization. Results have been conflicting regarding maternal Ramadan fasting and association with fetal outcomes in women without diabetes. Only one recently published study reported on perinatal outcomes in pregnant women with gestational diabetes which found no effect of Ramadan exposure on mean birthweight or macrosomia frequency but lower neonatal hypoglycemia prevalence, however a significant limitation was lack of documentation of maternal fasting status. At this stage, due to paucity of data, the current medical recommendation is against Ramadan fasting for pregnant Muslim women with diabetes. Large-scale population-based studies are warranted regarding maternal and fetal outcomes in pregnant fasting women with diabetes and such studies should characterize maternal fasting status and have meaningful and consistent clinical outcomes. High-quality data derived from these studies can assist clinicians in providing more evidence-based advice to safely navigate both mother and fetus through a potentially challenging pregnancy.

Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice.

The impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure. In this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months. A total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p<0.01), a reduction in the proportion of patients with New York Heart Association functional class III (40.4% to 16.2%, p<0.01), and a reduction in N-terminal pro-brain natriuretic peptide levels (969.5 ± 653.5 vs 577.4 ± 322.1 pgmL, p<0.01). Emergency department visits due to heart failure, hospitalizations due to heart failure, and all-cause hospitalizations also declined. Additionally, significant reductions in glycated hemoglobin (-1.4%) and body weight (-12.7 kilograms) were observed as well as a de-intensification of antidiabetic therapy. Moreover, semaglutide was safe and well-tolerated. In obese patients with type 2 diabetes and heart failure, the use of once-weekly semaglutide was safe and clinically efficacious, improving health and functional status. Nevertheless, more strong evidence on glucagon-like peptide-1 receptor agonists in heart failure is required.

Prediabetes Adherence to Nutrition Visits Decreases HbA1c in Children and Adolescents.

Prediabetes, the precursor of type 2 diabetes (T2D), is on the rise in the US, but the determinants of its progression are poorly characterized in youth. To determine the impact of nutrition visits, as a surrogate marker of lifestyle modification, on the trajectory of prediabetes over a 4-year period. Adherence to nutrition visits could reduce BMI and lower HbA1c. A 4-year retrospective study of 108 youth with prediabetes who were recommended to receive medical nutrition therapy every 3 months following their diagnosis. Subjects were divided into 2 groups the non-adherent group who had ≤1 nutrition visityear, and the adherent group with ≥2 nutrition visitsyear. There were 46 male subjects, mean age 12.4 ± 3.6y and 62 female subjects, mean age, 13.3 ± 3.0y, p0.2. The adherent group (n44, 41.5%) had higher BMI z-scores, but similar values for HbA1c, metformin use, and racialethnic composition compared to the non-adherent group. Overall, 18(17.0%) subjects progressed to T2D in 4y and consisted of 14(22.6%) of the 62 non-adherent subjects and 4(9.1%) of the 44 adherent subjects. The non-adherent subjects progressed to T2D at a mean duration of 25.8 ± 12.6 months while the adherent subjects progressed at a mean duration of 34.9 ± 11.8 months. The hazard ratio of progression from prediabetes to T2D for the non-adherent versus adherent group was 3.88 (95%CI 1.26-11.98, p0.02). The results remained significant after adjusting for age, sex, raceethnicity, BMI, and metformin use. Adherence to nutrition visits was associated with a 4-fold reduction in the likelihood to progress from prediabetes to T2D in US youth.

Identification of Up-Regulated ANXA3 Resulting in Fracture Non-Union in Patients With T2DM.

Diabetes mellitus is a metabolic disorder that increases fracture risk and interferes with bone formation and impairs fracture healing. Genomic studies on diabetes and fracture healing are lacking. We used a weighted co-expression network analysis (WGCNA) method to identify susceptibility modules and hub genes associated with T2DM and fracture healing. First, we downloaded the GSE95849, GSE93213, GSE93215, and GSE142786 data from the Gene Expression Omnibus (GEO) website, analyzed differential expression genes and constructed a WGCNA network. Second, we screened out 30 hub genes, which were found to be enriched in neutrophil activation, translational initiation, RAGE receptor binding, propanoate metabolism, and other pathways through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses. Third, we searched for genes related to bone metabolism and fracture healing in the published genome-wide single nucleotide polymorphism (SNP) data, built a protein-protein interaction (PPI) network with hub genes, and found that they were associated with metabolic process, blood vessel development, and extracellular matrix organization.

Association between thyroid hormones and skeletal muscle and bone in euthyroid type 2 diabetes patients.

The impact of thyroid hormones within their normal ranges on skeletal muscle and bone in patients with type 2 diabetes mellitus (T2DM) remains unknown. The purpose of this study was to investigate the relationships of thyroid hormones with muscle and bone in euthyroid patients with T2DM. This cross-sectional study included 344 euthyroid T2DM patients. Muscle mass and bone mineral density were measured by dual-energy X-ray absorptiometry. The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxin (FT4) were measured by electrochemiluminescence immunoassay. The results revealed that FT3 was positively correlated with body mass index (BMI) in male patients after age correction. In men, FT4 was negatively correlated with body weight, BMI, total muscle mass, appendicular skeletal muscle mass (ASM), and ASM index (ASMI), while FT3FT4 was positively correlated with body weight, BMI, total muscle mass, ASM, and ASMI after age correction. In women, FT4 was negatively correlated with ASM and ASMI, while FT3FT4 was positively correlated with ASM and ASMI after age correction. FT3FT4 was significantly lower in men with low muscle mass than in those with normal muscle mass. The age-adjusted odds for incident low muscle mass comparing the lowest and highest FT3FT4 increased in men. FT3FT4 was positively correlated with ASM and ASMI in both men and women. Therefore, FT3FT4 may be a parameter indicative of low muscle mass in euthyroid men with T2DM.

Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status A cross-sectional study using the UK Biobank data.

Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting. A cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status. A total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% ( Male smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria. University of Sheffield.

Effects of Yoga on Blood Glucose and Lipid Profile of Type 2 Diabetes Patients Without Complications A Systematic Review and Meta-Analysis.

Type II diabetes mellitus (T2DM) has become a worldwide public health problem. Although it has been empirically established that physical activity is a promising therapeutical approach to the prevention and management of T2DM, the effectiveness of yoga on T2DM has not yet reached an agreement across studies and also needs an updated synthetic examination. The purpose of this study was to examine the effect of yoga training on diabetes-related indicators compared with usual care. The review protocol of this study has been registered in the PROSPERO with a registration number CRD42021267868. A systematic literature search through electronic databases was conducted to identify yoga-based intervention (i.e., randomized controlled trial RCT e.g., yogic postures, movements, breathing, and meditation) studies reporting outcomes on glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PPBG), total cholesterol (TC), triglycerides (TG), and body mass index (BMI). A number of two researchers manually reviewed and assessed each article using the Cochrane Risk of Bias Tool 2.0. The literature search identified 296 eligible entries, of which 13 were finalized after screening using predefined inclusion and exclusion criteria. The extracted data (group mean and standard deviation at posttest) were synthesized using random-effects meta-analyses. Finally, potential moderators were explored using subgroup analysis and sensitivity analysis. The standardized mean difference for the effects of yoga was significant on HbA1c (MD -0.47 95%CI -0.77, -0.16 The findings suggest that yoga can improve the biochemical indices of blood glucose and the lipid profile of patients with T2DM. Therefore, yoga can be prescribed as an effective and active complementary treatment for T2DM. However, this study only tested yoga as a short-term treatment. In the future, rigorous RCTs with a larger sample size may be carried out to examine the long-term effect of yoga on T2DM. httpswww.crd.york.ac.ukPROSPEROdisplayrecord.phpRecordID267868, identifier CRD42021267868.

The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators A systematic review and network meta-analysis.

Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D. Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons. Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, -1.30% 95%CI -1.44, -1.16, P < 0.05) and body weight (MD, -3.17 kg 95%CI -3.89, -2.45, P < 0.05) compared to placebo (MD, HbA1c -0.32% 95%CI -0.49, -0.15, P < 0.05 MD body weight -2.56 kg 95%CI -3.41, -1.71, P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD -0.26% 95%CI -0.44, -0.07, P < 0.05) and body weight (MD -1.08 kg 95%CI -2.04, -0.12, P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide. Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.

The Significance of Exposure to Pregestational Type 2 Diabetes in Utero on Fetal Renal Size and Subcutaneous Fat Thickness.

To determine the relationship between exposure to pregestational type 2 diabetes (T2D) and renal size and subcutaneous fat thickness in fetuses during routine obstetrical ultrasound. This was a case-control study (January 1, 2019 to December 31, 2019). Routine obstetrical ultrasounds performed between 18 and 22 weeks gestation at a tertiary-care fetal assessment unit were reviewed. Cases comprised ultrasounds of fetuses exposed to pregestational T2D in utero. The control group was assembled from ultrasounds of healthy controls. Postprocessing measurements of fetal renal size and abdominal wall thickness from stored images were performed by two independent observers, and findings were compared between groups. There were 54 cases and 428 ultrasounds of healthy controls. The mean maternal age of cases was 32.1 years (SD 6.2) compared to 33.2 years (SD 5.3) for healthy controls, and the majority of ultrasounds were performed in multiparous patients (83%). At the 18 to 22 week ultrasound, there was a significant reduction in renal size amongst fetuses exposed to maternal T2D in utero compared to controls among cases, the mean renal width was 8.0 mm (95% CI 7.8-8.1) compared to 11.4 mm (95% CI 10.6-12.7) in controls ( Fetal renal size in cases exposed to pregestational T2D is significantly smaller compared to controls, and subcutaneous abdominal wall fat is significantly thicker. Given emerging evidence about the developmental origins of disease, further study is needed to correlate the association between fetal renal size and fat distribution in the fetus and the long-term risk of chronic renal disease and diabetes in these offspring.

Fourniers Gangrene in an HIV-Positive Patient on Empagliflozin for the Treatment of Diabetes Mellitus.

Fourniers gangrene is a severe polymicrobial infection that results in necrosis of the perineal and genital fasciae with rapid progression. This case report describes a 55-year-old male with a past medical history of HIV, type 2 diabetes, and hypertension who was diagnosed with Fourniers gangrene after the administration of empagliflozin (Jardiance). The patient presented with a worsening ulcer of the right groin and was diagnosed with Fourniers gangrene based on clinical and radiographic findings. He underwent surgical debridement of the wound. The patient was treated with empiric vancomycin, piperacillin-tazobactam, and clindamycin. Wound cultures grew

Bariatric Surgery With Roux-En-Y Gastric Bypass or Sleeve Gastrectomy for Treatment of Obesity and Comorbidities Current Evidence and Practice.

With the growing prevalence of obesity in the global population, alternative measures for weight loss and treatment of comorbidities must be considered due to the increasing difficulty of conservative management alone. Here we discuss the benefits of bariatric surgery on weight loss as well comorbidities that are present in a majority of obese patients. Methods In this review, we discuss the current practice and evidence of bariatric surgery as it pertains to weight loss and the beneficial effect on comorbidities commonly present in obesity. Our review found that bariatric surgery with either the roux-en-y gastric bypass or laparoscopic sleeve gastrectomy can result in weight loss of up to 80% of excess weight. We also found that bariatric surgery has a profound effect on multiple comorbidities such as type 2 diabetes mellitus, hypertension, and hyperlipidemia through remission of the disease. Bariatric surgery serves as an efficacious alternative for treatment of obesity and comorbidities.

Renal Autologous Cell Therapy to Stabilize Function in Diabetes-Related Chronic Kidney Disease Corroboration of Mechanistic Action With Cell Marker Analysis.

Chronic kidney disease (CKD) is a worldwide disease without cure. Selected renal cells (SRCs) can augment kidney function in animal models. This study correlates the phenotypical characteristics of autologous homologous SRCs (formulated product called Renal Autologous Cell Therapy REACT) injected into patients kidneys with advanced type 2 diabetes-related CKD (D-CKD) to clinical and laboratory findings. A total of 22 adults with type 2 D-CKD underwent a kidney biopsy followed by 2 subcortical injections of SRCs, 7 ± 3 months apart. There were 2 patients who had only 1 injection. We compared annualized estimated glomerular filtration rate (eGFR) slopes pre- and post-REACT injection using the 2009 CKD-EPI formula for serum creatinine (sCr) and the 2012 CKD-EPI Creatinine-Cystatin C equation and report clinicallaboratory changes. Fluorescent Activated Cell Sorting (FACS) Analysis for renal progenitor lineages in REACT and donor vascular endothelial growth factor A (VEGF-A) analysis were performed. Longitudinal parameter changes were analyzed with longitudinal linear mixed effects model. At baseline, the mean diabetes duration was 18.4 ± 8.80 years, glycated hemoglobin (Hgb) was 7.0 ± 1.05, and eGFR was 40.3 ± 9.35 mlmin per 1.73 m Our cell marker analysis suggests that SRCs may enable REACT to stabilize and improve kidney function, possibly halting type 2 D-CKD progression.

The magnitude of type 2 diabetes mellitus and cardiovascular disease risk factors among young adults in urban settings a cross-sectional survey in Mwanza, Tanzania.

traditionally, non-communicable diseases were diseases of public health concern in developed countries. Due to economic transition, they are becoming more prevalent in low and middle-income countries. Despite the trend, little has been done in the population of young adults of developing countries. This research aimed to explore the magnitude of type 2 diabetes mellitus, hypertension, dyslipidemia, and abdominal obesity among the young adult population in an urban setting of Tanzania. the current research used a cross-sectional community-based design, involving apparently healthy young adults aged 18 to 34 years, not known to have diabetes, hypertension, or dyslipidemia. Data on socio-demographic characteristics, medical history, anthropometry, blood pressure, and lipids were obtained per standard operating procedures and analyzed using STATA 13. Association between outcome variables (type 2 diabetes mellitus, hypertension, dyslipidemia, and abdominal obesity) and predictor variables (age, sex, education level, occupation, and economic status) were assessed by logistic regression. 245 young adults with a median age of 21 (interquartile range IQR 18-25) were recruited. Prevalence of diabetes mellitus and of impaired glucose tolerance (IGT) were 7.8% and 15.5% respectively. Abdominal obesity and dyslipidemia were present in 11.8% and 45.1% respectively. 34.3% had hypertension and the risk was significantly higher in males compared to females (OR 1.8, 95%CI 1.1, 3.1). The atherogenic coefficient was significantly associated with abdominal obesity other atherogenic indices did not show significant associations with current disease conditions. alarmingly high prevalence of diabetes mellitus, impaired glucose tolerance, hypertension, abdominal obesity, and dyslipidemia were observed among young adults in Mwanza. This study highlights the need for concerted efforts for interventions targeting young adults in combating diabetes and cardiovascular disease (CVD) risk factors in Tanzania.

Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mgkg and 400 mgkg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (

Cost-Effectiveness Analysis of Group vs. Weblog Telecommunication (Web Tel) Nutrition Education Program on Glycemic Indices in Patients With Non-Insulin Dependent Diabetes Mellitus Type 2 A Randomized Controlled Trial.

This a randomized controlled trial study with a cost-effectiveness analysis that aimed to compare the cost-effectiveness of group nutrition education with that of Web-Tel nutrition education in the glycemic control of patients with non-insulin-dependent type 2 diabetes mellitus (T2DM). The study was conducted on 105 patients with T2DM for 3 months in Quds health centre of Bushehr province, Iran. The participants were classified based on age and disease severity (hemoglobin A1c level) then, they were randomly assigned to one of the three groups group education, Web-Tel education, and the control group using block randomization method. The clinical (intermediate) outcome was changes in hemoglobin A1c (HbA1c). Patients perspective was adopted, and a deterministic one-way sensitivity analysis was conducted to identify the effects of uncertainties. The results indicated that the expected effectiveness was 0.46, 0.63, and 0.4 the mean costs was 27,188, 5,335, and 634 purchasing power parity (PPP) dollars for group education, Web-Tel education, and the control group, respectively. The incremental cost-effectiveness ratio (ICER) of Web-Tel education vs. the control group was positive and equal to $21, 613.04 PPP since it was less than three times of the threshold, the Web-Tel education method was considered as a more cost-effective method than the control group. On the other hand, the ICER of group education vs. control group was $447,067 PPP and above the threshold, so group education was considered as a dominated method compared with the control group. In conclusion, considering the ICER, Web-Tel education is a more cost-effective method than the other two and can be used as the first priority in educating patients with T2DM. The present study was registered in Thailand Clinical Trials Registry (TCTR20210331001).

Impact of Eating Speed on Muscle Mass in Older Patients With Type 2 Diabetes A Prospective Study of KAMOGAWA-DM Cohort.

Maintenance of muscle mass is important for sarcopenia prevention. However, the effect of eating speed, especially fast, normal, or slow speed, on muscle mass changes remains unclear. Therefore, the purpose of this prospective study was to investigate the effect of eating speed on muscle mass changes in patients with type 2 diabetes (T2DM). This study included 284 patients with T2DM. Based on a self-reported questionnaire, participants were classified into three groups fast-, normal-, and slow-speed eating. Muscle mass was assessed using a multifrequency impedance body composition analyzer, and skeletal muscle mass (SMI) decrease (kgm The proportions of patients with fast-, normal-, and slow-speed eating were, respectively, 50.5%, 42.9%, and 6.6% among those aged <65 years and 40.4%, 38.3%, and 21.3% among those aged ≥65 years. In patients aged ≥65 years, the rate of SMI decrease in the normal (0.85 95% confidence interval, CI -0.66 to 2.35) and slow (0.93 95% CI -0.61 to 2.46) speed eating groups was higher than that in the fast speed eating group (-1.08 95% CI -2.52 to 0.36). On the contrary, there was no difference in the rate of SMI decrease among the groups in patients aged <65 years. Compared with slow speed eating, the adjusted odds ratios of incident muscle loss defined as rate of SMI decrease (%) ≥0.5% due to fast- and normal-speed eating were 0.42 (95% CI 0.18 to 0.98) and 0.82 (95% CI 0.36 to 2.03), respectively. Slow-speed eating is associated with a higher risk of muscle mass loss in older patients with T2DM.

Obesity-Related Chronic Kidney Disease Principal Mechanisms and New Approaches in Nutritional Management.

Obesity is the epidemic of our era and its incidence is supposed to increase by more than 30% by 2030. It is commonly defined as a chronic and metabolic disease with an excessive accumulation of body fat in relation to fat-free mass, both in terms of quantity and distribution at specific points on the body. The effects of obesity have an important impact on different clinical areas, particularly endocrinology, cardiology, and nephrology. Indeed, increased rates of obesity have been associated with increased risk of cardiovascular disease (CVD), cancer, type 2 diabetes (T2D), dyslipidemia, hypertension, renal diseases, and neurocognitive impairment. Obesity-related chronic kidney disease (CKD) has been ascribed to intrarenal fat accumulation along the proximal tubule, glomeruli, renal sinus, and around the kidney capsule, and to hemodynamic changes with hyperfiltration, albuminuria, and impaired glomerular filtration rate. In addition, hypertension, dyslipidemia, and diabetes, which arise as a consequence of overweight, contribute to amplifying renal dysfunction in both the native and transplanted kidney. Overall, several mechanisms are closely related to the onset and progression of CKD in the general population, including changes in renal hemodynamics, neurohumoral pathways, renal adiposity, local and systemic inflammation, dysbiosis of microbiota, insulin resistance, and fibrotic process. Unfortunately, there are no clinical practice guidelines for the management of patients with obesity-related CKD. Therefore, dietary management is based on the clinical practice guidelines for the nutritional care of adults with CKD, developed and published by the National Kidney Foundation, Kidney Disease Outcome Quality Initiative and common recommendations for the healthy population. Optimal nutritional management of these patients should follow the guidelines of the Mediterranean diet, which is known to be associated with a lower incidence of CVD and beneficial effects on chronic diseases such as diabetes, obesity, and cognitive health. Mediterranean-style diets are often unsuccessful in promoting efficient weight loss, especially in patients with altered glucose metabolism. For this purpose, this review also discusses the use of non-classical weight loss approaches in CKD, including intermittent fasting and ketogenic diet to contrast the onset and progression of obesity-related CKD.

Interaction of Human Resistin with Human Islet Amyloid Polypeptide at Charged Phospholipid Membranes.

An X-ray reflectivity study on the interaction of recombinant human resistin (hRes) with fibrillation-prone human islet amyloid polypeptide (hIAPP) at anionic phospholipid Langmuir films as model membranes is presented. Aggregation and amyloid formation of hIAPP is considered the main mechanism of pancreatic β-cell loss in patients with type 2 diabetes mellitus. Resistin shows a chaperone-like ability, but also tends to form aggregates by itself. Resistin and hIAPP cross multiply metabolism pathways. In this study, we researched the potential protective effects of resistin against hIAPP-induced lipid membrane rupture. The results demonstrate that resistin can inhibit or prevent hIAPP adsorption even in the presence of aggregation-promoting negatively charged lipid interfaces. Moreover, we found strong hydrophobic interactions of resistin at the bare buffer-air interface.

Diagnostic and prognostic value of the electrocardiogram in stable outpatients with type 2 diabetes.

Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation, which could be exacerbated by type 2 diabetes mellitus (DM). We hypothesized that neutrophils in patients with DM and patients with HFpEF withwithout DM contribute to low-grade inflammation through the release of pro-inflammatory cytokines. Venous blood was withdrawn from patients with DM (n 22), HFpEF (n 15), HFpEF with DM (n 13), and healthy controls (CTL) (n 21). Levels of circulating cytokines and in vitro cytokines released by isolated neutrophils were assessed by enzyme-linked immunosorbent assay. Compared with CTL, there was a significant decrease in circulating nitric oxide in patients with DM (p ≤0.001), HFpEF (p ≤0.05), and HFpEF with DM (p ≤0.001) up to 44%. Circulating soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels increased (up to 2.5-fold and 1.9-fold, respectively p ≤0.001) in patients with HFpEF and patients with HFpEF and DM, whereas soluble E-selectin only increased in patients with HFpEF and DM (1.4-fold, p ≤0.001). Circulating vascular endothelial growth factor levels were similar in CTL and patients with DM but were decreased in patients with HFpEF withwithout DM (up to 94% p ≤0.001). Circulating C-reactive protein, interleukin (IL)-8, IL-6, and IL-receptor antagonist increased in all patient groups with a maximum of 3.3-fold, 4.7-fold, 4.8-fold, and 1.6-fold, respectively, in patients with HFpEF and patients with DM. In vitro, lipopolysaccharide increased neutrophils IL-6 release from HFpEF with DM (3.7-fold p ≤0.001), and IL-8 release from DM and HFpEF with DM versus CTL (2.8-fold and 10.1-fold, respectively p ≤0.001). IL-1 receptor antagonist and vascular endothelial growth factor release from HFpEF neutrophils significantly decreased up to 87.0% and 92.2%, respectively, versus CTL. Neutrophils from patients with DM and HFpEF release more cytokines than CTL. This increase in pro-inflammatory status may explain the greater event rate in patients with HFpEF and DM.

Generating pancreatic beta-like cells from human pluripotent stem cells.

Diabetes is a major healthcare burden globally, affecting over 463 million people today, according to the International Diabetes Federation. The most common types of diabetes are Type I diabetes (T1D) and Type II diabetes (T2D), characterized by hyperglycemia due to autoimmune destruction of β cells (T1D) and β cell dysfunction, usually on a background of insulin resistance (T2D). There is currently no cure for diabetes, and patients with T1D require lifelong insulin therapy. Additionally, while most cases of T2D can be managed by lifestyle and diet modifications, with or without antidiabetic drugs, severe cases of T2D may also require insulin therapy. The only means to restore stable euglycemia in these patients is now via whole pancreas or islet transplantation. However, this is limited by the scarcity of donors. In recent years, advances in human pluripotent stem cell (hPSC) technologies and pancreatic β cell differentiation protocols have opened up new potential avenues for cell replacement therapies for diabetes. These advances have also created opportunities to use hPSC-derived β-like cells for studies of disease mechanisms and drug discovery, which in turn have the potential to lead to better therapies for diabetes patients. Here, we describe the protocol used in our laboratory to generate β-like cells from hPSCs to study the mechanisms underlying various types of diabetes.

Butyrate oxidation attenuates the butyrate-induced improvement of insulin sensitivity in myotubes.

Skeletal muscle insulin resistance is a key pathophysiological process that precedes the development of type 2 diabetes. Whereas an overload of long-chain fatty acids can induce muscle insulin resistance, butyrate, a short-chain fatty acid (SCFA) produced from dietary fibre fermentation, prevents it. This preventive role of butyrate has been attributed to histone deacetylase (HDAC)-mediated transcription regulation and activation of mitochondrial fatty-acid oxidation. Here we address the interplay between butyrate and the long-chain fatty acid palmitate and investigate how transcription, signalling and metabolism are integrated to result in the butyrate-induced skeletal muscle metabolism remodelling. Butyrate enhanced insulin sensitivity in palmitate-treated, insulin-resistant C2C12 cells, as shown by elevated insulin receptor 1 (IRS1) and pAKT protein levels and Slc2a4 (GLUT4) mRNA, which led to a higher glycolytic capacity. Long-chain fatty-acid oxidation capacity and other functional respiration parameters were not affected. Butyrate did upregulate mitochondrial proteins involved in its own oxidation, as well as concentrations of butyrylcarnitine and hydroyxybutyrylcarnitine. By knocking down the gene encoding medium-chain 3-ketoacyl-CoA thiolase (MCKAT, Acaa2), butyrate oxidation was inhibited, which amplified the effects of the SCFA on insulin sensitivity and glycolysis. This response was associated with enhanced HDAC inhibition, based on histone 3 acetylation levels. Butyrate enhances insulin sensitivity and induces glycolysis, without the requirement of upregulated long-chain fatty acid oxidation. Butyrate catabolism functions as an escape valve that attenuates HDAC inhibition. Thus, inhibition of butyrate oxidation indirectly prevents insulin resistance and stimulates glycolytic flux in myotubes treated with butyrate, most likely via an HDAC-dependent mechanism.

Alpha-1 antitrypsin A novel biomarker and potential therapeutic approach for metabolic diseases.

It is well recognized that chronic low-grade systemic inflammation and autoimmunity contribute to the pathogenesis of metabolic syndrome, its associated diseases (e.g. type 2 diabetes, non-alcoholic fatty liver disease) and type 1 diabetes, respectively. Consequently, anti-inflammatory agents might play a role in managing these immune associated metabolic diseases. Alpha-1 antitrypsin (AAT), an endogenous acute phase protein being used for treatment of AAT deficiency (a rare genetic disease), has multiple functions including anti-inflammatory, immunomodulatory, anti-apoptosis and cytoprotective effects. In this review, we summarized basic and clinical studies that reported potential therapeutic role of AAT in metabolic syndrome associated diseases and type 1 diabetes. Studies that demonstrated AAT had the possibility to be used as a novel biomarker to predict these immune associated metabolic diseases were also included.

Dietary protein and multiple health outcomes An umbrella review of systematic reviews and meta-analyses of observational studies.

Numerous studies have evaluated the effects of dietary protein on specific health outcomes. The aim of our umbrella review was to summarize the existing evidence between the intake of dietary proteins and multiple health outcomes, and assess their strength and validity. Our study was registered at PROSPERO (No. CRD42021255938). We systematically searched PubMed, Embase, and Web of Science databases from inception to May 18, 2021, to identify relevant systematic reviews and meta-analyses of observational studies. The validated A Measurement Tool to Assess Systematic Reviews for assessing the methodological quality of included systematic reviews was utilized. For each association, we estimated the summary effect size using fixed and random effects methods, and the 95% confidence and prediction intervals. We also evaluated heterogeneity, evidence of small-study effects, and excess significance bias. Overall, 16 articles with 58 meta-analyses were included. All studies were categorized as over moderate quality. On employing the random-effects model, fourteen (24.1%) meta-analyses were found to be significant at P < 0.05, whereas only one (1.7%) remained significant at P < 10 Although the intake of dietary protein was associated with certain health outcomes, the strength of evidence was limited for most outcomes. Moreover, the source of dietary protein is an important factor that requires better consideration in future studies.

Study of toxoplasmosis in type 2 diabetic patients using ELISA and B1 nested-PCR methods.

Toxoplasma gondii (T. gondii) is a ubiquitous, opportunistic organism, which actually infects all warmblooded animals. Diabetes is a silent, irritating metabolic disorder among which type 2 diabetes includes over 90% of cases globally. This case-control study was aimed to detect T. gondii infection in type 2 diabetic patients in Khuzestan province, southwest of Iran. Serological enzyme-linked immunosorbent assay (ELISA) and molecular polymerase chain reaction (PCR) method targeting B1 gene were employed to comparatively detect the parasitic infection among 377 diabetic patients and 200 non-diabetic subjects during 2016-2018. Considerably higher anti-T. gondii antibodies were determined in case group 44.29% (167377), than in control group 19% (38200) (P<0.05). Among diabetic patients, 153 (40.58%) were seropositive for IgG and 14 (3.71%) were seropositive for IgM, while 35 (17.5%) and 3 (1.5%) healthy people were seropositive regarding IgG and IgM, respectively (P<0.05). By nested PCR, B1 gene was identified in 36 out of 167 (21.55%) and 5 out of 38 (13.15%) of the seropositive samples of case and control groups, respectively. The prevalence of anti-T. gondii antibodies and DNA in diabetic patients was significantly higher than in non-diabetic patients. Thus, it could be recommended to routinely evaluate the chronicity of the infection in diabetic patients.

Effect and mechanism of glycerol monostearate dimer (GMS-D) and baking-treatment on the structure, in vitro digestion of gelatinized potato starch-GMS-D.

With the increasing progress of society and in-depth scientific research, dietary regulations, especially sustained glucose releases, are regarded as an effective and significant way to lighten or even cut the emergence of diabetes. In this research, the starch-lipid complex gelatinized potato starch-glycerol monostearate dimer (GPS-GMS-D) was developed to provide a low-glycemic index functional food component for type 2 diabetes. Briefly, the higher complexation index (CI, 71.02%), lower rapidly digestible starch (RDS, 35.57%), and lower estimated glycemic index (eGI, 52.34%) were referred to as GPS-GMS-D. It was assumed that the solid V-type crystal structure, induced with the helix between GMS-D and GPS due to high amylose, high saturation, and low steric hindrance, contributed to the lower digestibility. In addition, baking treatment for 5 min was systematically exerted to improve the flavor of GPS-GMS-D with a relatively high CI (59.98%) and low eGI (54.15%). It was believed that rapid dehydration and close interaction during baking treatment could slow down the decomposition of GPS-GMS-D and conversions of starch fractions. Therefore, these results suggested that the as-developed GPS-GMS-D was a promising low GI functional dietary food component for diabetes mellitus, and a suitable baking post-thermal treatment was successfully proposed to enhance the flavor of GPS-GMS-D. PRACTICAL APPLICATION The higher amylose and solid V-type crystal structure in gelatinized potato starch-glycerol monostearate dimer (GPS-GMS-D) would induce the formation of slowly digestive starch (SDS) and resistant starch (RS) to suppress enzymatic hydrolysis. Moreover, the flavor of GPS-GMS-D was enhanced with appropriate and moderate thermal processing (baking), which was likely to improve the quality of life of a person with diabetes. Thus, we believe that GPS-GMS-D is a promising functional food component for diabetes mellitus.

Impact of chronic hepatitis on cardiovascular events among type 2 diabetes patients in Taiwan pay-for-performance program.

To investigate the impact of chronic hepatitis on cardiovascular events in patients with type 2 diabetes mellitus (T2DM). This nationwide retrospective cohort study included 152,709 adult patients (> 20 years) with T2DM enrolled in the National Health Insurance Diabetes Pay-for-Performance Program from 2008 to 2010 and followed up until the end of 2017. Patients were categorized into groups with hepatitis B, hepatitis C, fatty liver disease, and patients without chronic hepatitis. The incidence of cardiovascular events in patients with T2DM and hepatitis C (79.91000 person-years) was higher than that in patients with diabetes combined with other chronic hepatitis, or without chronic hepatitis. After adjusting for confounding factors, T2DM with fatty liver (adjusted hazard ratio HR 1.10 95% confidence interval CI 1.07-1.13) and hepatitis C (adjusted HR 1.09 95% CI 1.03-1.12) demonstrated a significantly higher risk of cardiovascular events. The adjusted visit-to-visit coefficient of variation of HbA1c and fasting blood glucose were associated with a high risk of cardiovascular events (HRs of the highest quartile were 1.05 and 1.12, respectively). Chronic hepatitis affects cardiovascular events in adult patients with T2DM. Glucose variability could be an independent risk factor for cardiovascular events in such patients.

Resistance Training as a Countermeasure in Women with Gestational Diabetes Mellitus A Review of Current Literature and Future Directions.

Gestational diabetes mellitus (GDM) poses a significant health concern for both mother and offspring. Exercise has emerged as a cornerstone of glycemic management in GDM. However, most research regarding this topic examines aerobic training (AT), despite substantial evidence for the effectiveness of resistance training (RT) in improving dysregulated glucose in other groups of people with diabetes, such as in type 2 diabetes mellitus (T2DM). Thus, the purpose of this paper is to review research that examined the impact of RT on markers of glucose management in GDM, and to discuss future research directions to determine the benefits of RT in GDM. Based on the current evidence, RT is effective in reducing insulin requirement, especially in overweight women, reducing fasting glucose concentrations, and improving short-term postprandial glycemic control. However, the number of studies and findings limit conclusions about the impact of RT on risk of GDM, fasting insulin concentrations, insulin resistance, β-cell function, and intra-exercise glucose management. Overall, current evidence is accumulating to suggest that RT is a promising non-pharmacological tool to regulate circulating glucose concentrations in women with GDM, and a potential alternative or supplement to AT.

A new perspective on diabetes distress using the type 2 diabetes distress assessment system (T2-DDAS) Prevalence and change over time.

To establish cut-points and thresholds for elevated diabetes distress document change over time and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS). A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational threshold approach defined elevated SOURCE scores. 471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8 % (69.9 % over 6 months). Elevated SOURCE scores varied from 30.6 % (StigmaShame) to 76.4 % (Management) 87.5 % indicated at least 1 elevated SOURCE score. Most (77.1 %) reported multiple elevated SOURCES. 81.8 % with elevated CORE distress at baseline remained elevated at 6 months. MCID analyses yielded - 0.25 as significant change. Few differences between insulin- and non-insulin users occurred. Elevated CORE distress is highly prevalent and persistent over time most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

A comprehensive risk assessment for nocturnal hypoglycemia in geriatric patients with type 2 diabetes A single-center case-control study.

To evaluate the overall association between clinically significant nocturnal hypoglycemia (CsNH) and risk factors in geriatric patients with type 2 diabetes. Overall, 606 geriatric with type 2 diabetes were evaluated for CsNH using Freestyle Libre Pro® (Abbott Diabetes Care, Tokyo, Japan) during October 2018-February 2020. We defined CsNH as blood glucose level <54 mgdL (3.0 mmolL). We investigated clinical characteristics and efficacies of hypoglycemic agents and insulin and analyzed CsNH risk factors using univariate and multivariate logistic regression analyses. We enrolled 152 patients each for the CsNH and non-nocturnal hypoglycemia groups. Insulin use (OR 3.77 95 % CI 1.92-7.67 P 0.0002), age (OR 1.06 95 % CI 1.01-1.12 P 0.0492), estimated glomerular filtration rate (OR 0.97 95 % CI 0.95-0.98 P 0.0492), and fasting blood glucose level (OR 0.94 95 % CI 0.91-0.94 P < 0.0001) were independent CsNH risk factors. The combined results demonstrated a higher predictability of CsNH than each of the individual risk factors. We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

Effect of Sodium-Glucose Cotransporter Inhibitors on Major Adverse Cardiovascular Events and Hospitalization for Heart Failure in Patients With Type 2 Diabetes Mellitus and Atrial Fibrillation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to lower cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risks. Here, we aimed to evaluate the effect of SGLT2 inhibitors on major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, myocardial infarction, or ischemic stroke and hospitalization for heart failure in patients with T2DM and atrial fibrillation (AF). Using the Korean National Health Insurance Service database, we identified 40,268 patients with T2DM and AF who were newly prescribed oral hypoglycemic drugs (2,977 patients with SGLT2 inhibitors and 37,291 patients without SGLT2 inhibitors) between 2014 and 2018. After 1 4 propensity score matching, patients who received SGLT2 inhibitors (n 2,958) and those who did not receive SGLT2 inhibitors (n 10,691) were enrolled, and followed up until December 31, 2018. During a mean follow-up duration of 2.1 ± 1.4 years, the risk of major adverse cardiovascular events was similar between the 2 groups (hazard ratio HR 0.96, 95% confidence interval CI 0.76 to 1.21). There were no significant differences between the 2 groups for cardiovascular mortality, myocardial infarction, or ischemic stroke. However, patients who received SGLT2 inhibitors had significantly lower risks of hospitalization for heart failure (HR 0.70, 95% CI 0.53 to 0.93) and all-cause mortality (HR 0.74, 95% CI 0.56 to 0.98) than those who did not receive SGLT2 inhibitors. In conclusion, in this real-world cohort of Asian patients with T2DM and AF, use of SGLT2 inhibitors was associated with a lower risk of hospitalization for heart failure.

All-cause mortality prediction in T2D patients with iTirps.

Mortality in the type II diabetic elderly population can sometimes be prevented through intervention, for which risk assessment through predictive modeling is required. Since Electronic Health Records data are typically heterogeneous and sparse, the use of Temporal Abstraction and time intervals mining to discover frequent Time Intervals Related Patterns (TIRPs) is employed. While TIRPs are used as features for a predictive model, the temporal relations between them in general, and among each TIRPs instances are not represented. We introduce a novel TIRP based representation called integer-TIRP (iTirp) in which the TIRPs become channels containing values that represent the TIRP instances that were detected at each time point. Then the iTirp representation is fed into a Deep Learning architecture, that learns this kind of temporal relations, using a Recurrent Neural Network or a Convolutional Neural Network. Additionally, a predictive committee is introduced in which raw data and iTirp data are concatenated as inputs. Our results show that iTirps based models outperform the use of deep learning with raw data, resulting in 82% AUC.

A technology assisted precision ketogenic diet intervention for cardio-renal-metabolic health in overweight or obese adults Protocol for a randomized controlled trial.

The obesity epidemic is a public health concern, as it is associated with a variety of chronic conditions. The ketogenic diet has drawn much scientific and public attention. However, implementation is challenging and its effect on cardio-renal-metabolic health is inconclusive. This study will assess the feasibility, acceptability, and preliminary efficacy of a technology-assisted ketogenic diet on cardio-renal-metabolic health. This is a single center, 6-month, stratified, randomized controlled trial. A total of 60 overweightobese adults (18 years old) will be enrolled, including 20 without type 2 diabetes (T2D) and without chronic kidney disease (CKD) 20 with T2D, but without CKD and 20 with early-stage CKD. Participants will be stratified based on health conditions and randomized into a ketogenic diet (n 30) or a low-fat diet group (n 30). Health education involving diet and physical activity will be delivered both digitally and in-person. Mobile and connected health technologies will be used to track lifestyle behaviors and health indicators, as well as provide weekly feedback. The primary outcome (weight) and the secondary outcomes (e.g., blood pressure, glycemic control, renal health) will be assessed with traditional measurements and metabolomics. Mobile and connected health technologies provide new opportunities to improve chronic condition management, health education attendance, planned lifestyle changes and engagement, and health outcomes. The advancement of bioinformatics technology offers the possibility to profile and analyze omics data which may advance our understanding of the underlying mechanisms of intervention effects on health outcomes at the molecular level for personalized and precision lifestyle interventions.

The role of Kimmelstiel-Wilson nodule in the kidney outcome in patients with diabetic kidney disease A two-center retrospective cohort study.

In the current study, we aimed to investigate the predictive value of the Kimmelstiel-Wilson (K-W) nodule for the risk of ESKD in patients with type 2 diabetes mellitus (T2DM). In the two-center retrospective study, clinical and pathological parameters were compared between DKD patients with and without K-W nodules. Furthermore, we used Cox regression analysis to explore the predictive value of the K-W nodule for the risk of ESKD. Compared with DKD patients without K-W nodules, patients with K-W nodules had a significantly higher level of proteinuria 5.1(3.1, 8.0) g24 hr vs. 2.4(1.1, 4.4) g24 hr, p < 0.001. Patients with K-W nodules had significantly higher interstitial fibrosis and tubular atrophy (IFTA) and arteriosclerosis scores than those without (p 0.001 and p 0.006). Kaplan-Meier analysis showed that the probability of developing ESKD was significantly higher in patients with K-W nodules than in those without (log-rank test, p < 0.001). However, after adjusting closer variables, the K-W nodule was not an independent predictor for the risk of ESKD (p > 0.05). In T2DM patients with DKD, the K-W nodule was associated with a more severe phenotype, and to some extent, associated with poorer renal outcome, but might not be an independent risk factor for the progression of ESKD.

Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to severe COVID-19 patients, irrespective of pre-existing glycemic status.

To compare admission-blood-glucose (ABG) or stress-hyperglycemia-ratio (SHR) performs better in predicting mortality and worse outcomes in COVID-19 patients with (DM) and without known Type 2 Diabetes Mellitus (UDM). ABG and SHR were tested for 451 patients with moderate-severe COVID-19 infection DM 216,47.9% pre-diabetes 48,10.6%, UDM 187,41.4%,who were followed-up to look for in-hospital-mortality (primary outcome) and secondary outcomes (ICU stay or mechanical ventilation, hospital-acquired-sepsis and multiple organ dysfunction syndrome MODS). Those with and without SHR ≥ 1.14 were compared logistic regression was done to identify predictors of outcomes, with subgroup analysis based on pre-existing DM status and COVID-19 severity. Those who died (n 131) or developed ≥ 1 secondary outcomes (n 218) had higher prevalence of SHR ≥ 1.14, ABG ≥ 180 mgdl and higher median SHR (p SHR better predicts mortality and adverse outcomes than ABG in patients with COVID-19, irrespective of pre-existing chronic glycemic status.