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Summary: This study aimed to evaluate the efficacy and safety of duodenal–jejunal bypass liner (DJBL) for obesity and type 2 diabetes mellitus. A comprehensive search of electronic databases was conducted up to September 15, 2022. Thirty studies involving 1751 patients were included. At 12 months post‐implantation, the reduction in body mass index (BMI) was 4.8 kg/m2 (95% CI 4.1, 5.5), with an excess weight loss of 41.3% (95% CI 33.4%,49.2%) and a total weight loss of 13.1% (95% CI 10.1%, 16.0%). Significant decrease was observed in HbA1c and fasting glucose, with a standardized mean difference of − 0.72 (95% CI − 0.95, − 0.48) and − 0.62 (95% CI − 0.82, − 0.42), respectively. However, these improvements in weight loss and glycemic control were only partially sustained after explantation. In situ, DJBL significantly improves blood pressure and lipid levels. The pooled early removal rate was 19%, and the incidence of severe adverse events was 17%, including device migration (6%), gastrointestinal hemorrhage (4%), device obstruction (4%), and hepatic abscess (2%). DJBL offers significant improvement in weight loss and glycemic control, as well as cardiovascular parameters while in situ. Further studies are warranted to better understand the long‐term efficacy and safety of DJBL. The benefits of DJBL need to be carefully weighed against the risks in clinical decision‐making. [ABSTRACT FROM AUTHOR]

Aim: To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout‐related outcomes. Materials and Methods: Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3–5.1 mg/dL [>255.8–303.4 µmol/L], >5.1–5.8 mg/dL [>303.4–345.0 µmol/L], >5.8–6.9 mg/dL [>345.0–410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti‐gout medication was assessed. Results: The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6–260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (−0.02, 0.15) and −0.19 mg/dL (−0.25, −0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo‐adjusted LSM change (95% CI) from baseline in UA was −0.26 mg/dL (−0.36, −0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout‐related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002]). Conclusions: Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout‐related outcome events. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM). Research Design and Methods: A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement guidelines were followed for this meta‐analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta‐analysis was performed using random‐effect models. Results: Eighteen studies met the objectives of this meta‐analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15–1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30–1.65) for CV groups, HR 1.32 (95% CI 1.10–1.57) for HVS groups and HR 1.53 (95% CI 1.05–2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17–1.35), and 1.13 (95% CI 1.03–1.23), respectively. Also, each 1‐SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07–1.29). Conclusions: The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between changes in haemoglobin A1c (HbA1c) and the concurrent incidence of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients. Method: We conducted a retrospective cohort study among T2DM patients with HbA1c measurement after T2DM diagnosis between August 2009 and September 2010. The patients were classified into six subgroups based on baseline HbA1c (<7%; 7%–7.9%; ≥8%) and age (<65; ≥65 years), and then clustered into classes by HbA1c trajectory and CVD incidence over the 12‐year follow‐up period using joint latent class mixture models. We explored the HbA1c trajectories and CVD incidences in each latent class. Multinomial logistic regression was used to compare the baseline characteristics among different latent classes. Results: A total of 128 843 T2DM patients were included with a median follow‐up period of 11.7 years. Ten latent classes were identified in patients with baseline HbA1c ≥ 8% and age <65 years, while seven classes were identified in the other five groups. Among all the identified latent classes, patients with fluctuating HbA1c trajectories, characterized by alternating periods of increase and decrease, had higher CVD incidences. Male patients, and patients with higher baseline HbA1c and use of antidiabetic drugs were more likely to have a fluctuating HbA1c trajectory. More specifically, patients aged < 65 years with younger age or a smoking habit, and patients aged ≥ 65 years with a longer duration of T2DM were more likely to have a fluctuating HbA1c trajectory. Conclusion: We found that T2DM patients with fluctuating HbA1c trajectories could have a higher CVD risk. Different trajectory‐associated characteristics in age subgroups highlight the need for individualized management of T2DM patients. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add‐on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. Patients and Methods: In this multicentre, randomized, double‐blind, placebo‐controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable‐dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. Results: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was −0.70% (−7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2‐h postprandial plasma glucose, fasting insulin, uric acid and gamma‐glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. Conclusion: Dapagliflozin add‐on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions This study aims to investigate the relationship between long‐term visit‐to‐visit within‐person HbA1c variability and hospitalisation outcomes in adults with type 2 diabetes (T2D).We conducted a cohort study at a tertiary hospital in Singapore involving people aged 21 to 101 years with T2D who had ≥3 HbA1c tests over 2 years. HbA1c variability was assessed using coefficient of variation (CV), variability independent of the mean (VIM) and HbA1c variability score (HVS). A 1‐year follow‐up was performed after the last HbA1c measurement to identify all‐cause and potentially avoidable hospitalisations (PAH), categorised as overall, acute, chronic and diabetes composites.The study included 14 923 patients (mean age: 62.9 ± 12.9 years; 55% male). The median HbA1c variability was 8.6% CV (IQR: 5.1–14.3). Higher quartiles of HbA1c variability were associated with greater risks of PAH and all‐cause hospitalisations, independent of glycaemic control. Compared to Q1, for example, the risk ratios and 95% confidence intervals for diabetes‐related PAH based on HbA1c CV were as follows: Q2, 1.32 (0.93–1.88); Q3, 1.65 (1.18–2.31) and Q4, 2.16 (1.54–3.03). For all‐cause hospitalisations, they were as follows: Q2, 0.97 (0.90–1.05); Q3, 1.08 (1.00–1.17) and Q4, 1.16 (1.07–1.26). When stratified by glycaemic control, elevated risk of PAH persisted even in those with optimal glycaemic control. Consistent findings were observed using HbA1c VIM and HVS measures.In individuals receiving care at specialist outpatient clinics of a tertiary hospital, HbA1c variability is associated with a higher risk of PAH. Comprehensive diabetes management strategies addressing both glycaemic control and variability may offer benefits. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) remains a global health concern, causing a significant threat to world health. Oral anti‐diabetic drugs play a crucial role in effective management of diabetes. Numerous anti‐diabetic medications have been known for a long period, classified according to their chemical groups but because of their low pharmaceutical cost and long‐term efficacy, sulphonylurea (SU) continues to be a well‐positioned medication with a long history of clinical use in treating type 2 diabetes. Among various available SU, Gliclazide stands out due to its significant reduction in cardiovascular mortality and extremely low rate of severe hypoglycaemia. Numerous synthetic methodologies have been developed to create more efficient pathways resulting in less waste and cheaper manufacturing. The present review aims to summarise some recently reported literature for the synthesis of Gliclazide. We have made an effort to highlight their drawbacks and advantages in this comparative analysis. Here we tried to compile different synthetic routes via various methods to synthesise Gliclazide which will serve as a valuable foundation to make potential modifications to the present inventions. This effort ultimately aims to contribute to the enhancement of the society's health and welfare. [ABSTRACT FROM AUTHOR]

Introduction Objectives Methods Results Conclusion There is a paucity of data evaluating early initiation of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG).To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS.This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABG with follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4‐point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30‐day readmission rates, and subgroup analyses of key populations.A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41–1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45–1.01).Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium–glucose cotransporter‐2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome.We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135–145 mmol/L) and follow‐up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021.After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non‐steroidal anti‐inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow‐up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83–3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16–2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73–2.96) and all‐cause death (HR: 2.98; 95% CI: 2.17–4.11) after adjusting for clinically relevant factors. Non‐linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events.While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk. [ABSTRACT FROM AUTHOR]

Recently, molecular hybridization strategy has paved a way to develop novel lead compounds for the α‐amylase targeted antidiabetic therapy. In this study, we disclosed a series of new hybrids of thiazolidine‐2,4‐diones with 2‐chloroquinoline‐3‐yl moiety as potential antidiabetic agents. The molecular structures of all the synthesized hybrids (15a–n) were confirmed by spectroscopic studies (FT‐IR, ESI‐MS, 1H, 13C NMR, and elemental analysis). When in vitro antidiabetic evaluation of these agents was carried out in a dose‐dependent manner, it was revealed that several compounds (15f–h, 15j, and 15n) were endowed with significant antidiabetic activities and exhibited more than 50% α‐amylase inhibition at a dose of 50 µg/mL. Particularly, hybrid 15n was found to be more potent than acarbose with 95% inhibition of α‐amylase and IC50 of 5.00 ± 0.18 µM under given conditions. Further, it was demonstrated that 15n bearing 2‐chloroquinolinyl and thiazolidin‐2,4‐dione scaffolds functionalized with 3‐OMe and 4‐OH groups was not only able to effectively bind with α‐amylase receptor site with best docking score (−9.644 kcal/mol) but also possessed drug‐likenesses properties with no violations of Lipinski rule. Overall, this study discovered new 2‐chloroquinolinyl‐thiazolidine‐2,4‐diones hybrids as novel α‐amylase inhibitors and compound 15n as promising lead for its further development as antidiabetic agent. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To explore the association between the non‐high‐density lipoprotein cholesterol (HDL‐C)/HDL‐C ratio (NHHR) and the risk of major adverse cardiovascular events (MACEs) and overall mortality in patients with type 2 diabetes mellitus (T2DM).NHHR, calculated as (total cholesterol – HDL‐C)/HDL‐C, was evaluated in 10,188 participants. Cox proportional hazard regression models were employed to assess the association of NHHR with future risk of MACEs and overall mortality. Restricted cubic spline analysis, smooth curve fitting and piecewise regression models were utilized to explore the non‐linear correlation and establish the threshold. Subgroup and interaction analyses verified the robustness of the findings. The area under the receiver operating characteristic area under the curve assessed the additional predictive value of NHHR beyond conventional risk factors.After adjusting for confounding factors, each 1‐unit increase in NHHR was associated with a 12% increased risk of MACEs (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.07–1.16; p < 0.0001), a 5% increase in overall mortality (HR: 1.05, 95% CI: 1.01–1.10; p = 0.0256), a 10% increase in cardiovascular disease mortality (HR 1.10, 95% CI: 1.03–1.18; p = 0.0074), an 12% increase in non‐fatal myocardial infarction (HR: 1.12, 95% CI: 1.05–1.18; p = 0.0002), and an 11% increase in non‐fatal stroke (HR: 1.11, 95% CI: 1.02–1.20; p = 0.0123). Analyses showed a non‐linear relationship between NHHR and MACEs in patients with T2DM (non‐linearity p < 0.001). A two‐stage linear regression model identified a threshold for MACEs at 6.28. Integration NHHR into the conventional model significantly enhanced predictive accuracy for MACEs.NHHR is a predictor of the risk of developing MACEs and overall mortality in patients with T2DM, with higher NHHR values independently associated with increased future MACE risks after full adjustment for confounders. [ABSTRACT FROM AUTHOR]

Background: Individuals with type 2 diabetes mellitus (T2DM) are prone to musculoskeletal complications, particularly in the upper extremities (UE), which can significantly impair their grip strength and UE muscle strength. This review will provide valuable insights for developing optimized exercise interventions aimed at enhancing upper limb functionality and improving patient outcomes. Aim: To determine the effect of different exercise training on grip strength & UE muscle strength in patients suffering from T2DM. Methodology: A comprehensive search from electronic databases was performed based on the selection criteria and 13 randomized controlled trials (RCT's) were included in the study. Mean changes in grip strength and UE muscle strength were the primary outcome measures. Included studies ranked high on the PEDro rating scale and eta‐analysis was performed by Rev Man 5.4 software. Results: Meta‐analysis results indicated that there was a statistically significant improvement in UE muscle strength of experimental group when compared to control group (mean differences [MD] = 2.91, 95% confidence interval = 0.12, 5.71; p = 0.04) with moderate heterogeneity (I2 = 49%, p < 0.07). Grip strength improved significantly in the experimental group when compared to the control group with (MD = 2.93, 95% CL = −0.00, 5.86; p = 0.05) and moderate heterogeneity (I2 = 66%, p < 0.08). Conclusion: This review indicated a positive role of supervised resistance & aerobic exercises on UE muscle strength in patients with T2DM. Due to lack of RCT's, grip strength needs to be explored by further investigations in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to examine the alterations in subcortical brain volume and cortical thickness among individuals diagnosed with Type 2 diabetes mellitus (T2DM) through the application of morphometry techniques and, additionally, to investigate the potential association between these modifications and insulin resistance (IR). Materials and methods: The present cross‐sectional study comprised a total of 121 participants (n = 48 with healthy controls [HCs] and n = 73 with T2DM) who were recruited and underwent a battery of cognitive testing and structural magnetic resonance imaging (MRI). FreeSurfer was used to process the MRI data. Analysis of covariance compared discrepancies in cortical thickness and subcortical brain volume between T2DM and HCs, adjusting for the potential confounding effects of gender, age, education, and body mass index (BMI). Exploratory partial correlations investigated links between IR and brain structure in T2DM participants. Results: Compared with HCs, individuals with T2DM demonstrated a cortical thickness decrease in the right caudal middle frontal gyrus, right pars opercularis, left precentral gyrus, and bilateral superior frontal gyrus. Furthermore, this study for T2DM found that the severity of IR was inversely related to the volume of the left putamen and left hippocampus, as well as the thickness of the left pars orbitalis, left pericalcarine, right entorhinal area, and right rostral anterior cingulate gyrus. Conclusion: The evidence for structural brain changes in T2DM was observed, and alterations in cortical thickness were concentrated in the frontal lobes. Correlations between IR and frontal cortical thinning may serve as a potential neuroimaging marker of T2DM and lead to various diabetes‐related brain complications. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has become a major chronic disease seriously affecting human health. Type 2 diabetes mellitus (T2DM) accounts for about 90% of DM patients, which is the largest type. Approximately 25–35% of T2DM patients develop kidney disease, which not only impacts the survival rate and quality of life but also, to the family and society, are of great economic burden. Early identification of high‐risk T2DM patients with kidney disease is crucial for initiating targeted prevention and treatment measures in time to reduce or delay the occurrence and progression of diabetic kidney disease. Previous studies have identified a variety of clinical predictors for the progression of renal function in T2DM patients, including proteinuria, estimated glomerular filtration rate, blood glucose, blood pressure, serum uric acid, dyslipidemia, obesity, smoking, duration of DM, age, gender, race, family history of DM, and diabetic retinopathy. Clinical prediction models based on conventional clinical indicators are instrumental in evaluating the risk of kidney disease in T2DM patients, assisting in patient risk stratification. This article systematically reviews the clinical prediction factors and prediction models associated with the progression of renal function in T2DM patients, providing a comprehensive and current reference for improved clinical assessment of the risk of renal function progression. [ABSTRACT FROM AUTHOR]

Aims: Health education is integral to cardiometabolic disease (CMD) management. This study aimed to assess whether and how education preferences have changed over time, and whether trends differ by sociodemographic characteristics (education status, age, ethnicity, and sex). Methods: A cross‐sectional questionnaire was deployed across five counties in the East Midlands, UK between 2017 and 2022 to adults with CMD (type 2 diabetes, cardiovascular disease or cerebrovascular disease). Respondent demographic data were collected alongside health education preferences. Statistical analyses ascertained whether demographic characteristics influenced preferences. The distribution of preferences over time was charted to identify trends. Results: A total of 4301 eligible responses were collected. Face‐to‐face one‐to‐one education was preferred (first choice for 75.1% of participants) but popularity waned over the five‐year period. Trends were similar amongst demographic groups. Online education showed a U‐shaped trend: In 2017, 44% of respondents ranked it as acceptable, peaking at 53% in 2019, but declining again, to below base line, 43%, by 2022. This modality was more popular with participants aged younger than 65 years, but popularity in people older than 65 years increased over the study period. The popularity of printed information also declined over time across all demographic groups except those of South Asian ethnicity, for whom it remained static. Conclusions: The overwhelming preference for face‐to‐face one‐to‐one health education from a doctor or nurse highlights the importance of preserving access to this modality, even in the face of current NHS pressures and trends towards digitalisation. Trends are changing, and should continue to be monitored, including between different sociodemographic groups. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is widely recognized as a serious global public health concern with a substantial economic burden on patients, their families, and society. Accumulating evidence suggests that an etiologic role for serum microbiota and circulating metabolites in the pathogenesis of T2DM. This study aims to characterize the serum microbiota and circulating metabolites in cynomolgus monkeys with spontaneous T2DM, and provide a reference for the diagnosis and treatment of clinical T2DM. Methods: We collected serum samples of the 14 cynomolgus monkeys (15–20 years old, male) for serum microbiota analysis by 16S rRNA gene V3‐V4 region amplicon sequencing and circulating metabolites analysis by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, of which seven were spontaneous T2DM cynomolgus monkeys and seven were healthy controls. Results: Our results showed that the serum microbiota abundance and diversity were significantly increased in cynomolgus monkeys with spontaneous T2DM compared to healthy controls, the phyla of Cyanobacteria and Chloroflexi and the genera of Lactobacillus, rhodobacter and collinsella were also significantly increased. A total of 114 serum differentially expressed metabolites (DEMs) were identified, of which 22 were selected as potential biomarkers candidates related to spontaneous T2DM in cynomolgus monkeys by multivariate data analysis. In addition, serum levels of total SCFAs, acetate, butyrate, caproate, isobutyrate, and isovalerate were also significantly increased in the present study. The correlation network analyses have selected certain key DEMs, such as D‐Psicose, 4‐Oxoproline, D‐Glutamine, and Hydroxyphenyllactic acid, which may serve as potential biomarkers for distinguishing between T2DM and healthy controls. Conclusion: Our results provide preliminary insights on perturbed serum microbiota and circulating metabolites of cynomolgus monkeys with spontaneous T2DM. These findings would be useful to develop microbiota‐based strategies for T2DM prevention and control. [ABSTRACT FROM AUTHOR]

Impulsivity has been proposed to have an impact on glycemic dysregulation. However, it remains uncertain whether an unfavorable glycemic status could also contribute to an increase in impulsivity levels. This study aims to analyze associations of baseline and time‐varying glycemic status with 3‐year time‐varying impulsivity in older adults at high risk of cardiovascular disease. A 3‐year prospective cohort design was conducted within the PREDIMED‐Plus‐Cognition substudy. The total population includes 487 participants (mean age = 65.2 years; female = 50.5%) with overweight or obesity and metabolic syndrome. Insulin resistance (HOMA‐IR), glycated hemoglobin (HbA1c), presence of type 2 diabetes mellitus, and type 2 diabetes control were evaluated. Impulsivity was measured using the Impulsive Behavior Scale questionnaire and various cognitive measurements. Impulsivity z‐scores were generated to obtain Global, Trait, and Behavioral Impulsivity domains. Linear mixed models were used to study the longitudinal associations across baseline, 1‐year, and 3‐year follow‐up visits. HOMA‐IR was not significantly related to impulsivity. Participants with higher HbA1c levels, type 2 diabetes, and poor control of diabetes showed positive associations with the Global Impulsivity domain over time, and those with higher HbA1c levels were further related to increases in the Trait and Behavioral Impulsivity domains over the follow‐up visits. These results suggest a potential positive feedback loop between impulsivity and glycemic‐related dysregulation. [ABSTRACT FROM AUTHOR]

Aims/Introduction: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. Materials and Methods: This is a historical cohort study including 342,033 participants (aged 18–72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. Results: The median follow‐up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD−/CeVD−, CAD+/CeVD−, CAD−/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person‐years in non‐diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD−/CeVD−/non‐diabetes were 1.66 (95% confidence interval 1.55–1.78) in CAD−/CeVD−/type 2 diabetes and 1.84 (1.56–2.18) in CAD+/CeVD−/non‐diabetes. CeVD+ was linked to a 4‐7‐fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. Conclusions: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: This nationwide cohort study evaluated the impact of sodium–glucose co‐transporter‐2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i‐treated patients and those not receiving SGLT2i. Materials and Methods: Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow‐up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. Results: After propensity score matching, compared with the non‐SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34–0.88; p = 0.0131) and a significant reduction in all‐cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39–0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. Conclusions: Our findings indicate significantly lower risks of recurrent IS and all‐cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects. [ABSTRACT FROM AUTHOR]

Aim: To develop and test different machine learning algorithms for predicting nocturnal hypoglycaemia in patients with type 2 diabetes mellitus. Design: A retrospective study. Methods: We collected data from dynamic blood glucose monitoring of patients with T2DM admitted to the Department of Endocrinology and Metabolism at a hospital in Shanghai, China, from November 2020 to January 2022. Patients undergone the continuous glucose monitoring (CGM) for ≥ 24 h were included in this study. Logistic regression, random forest and light gradient boosting machine algorithms were employed, and the models were validated and compared using AUC, accuracy, specificity, recall rate, precision, F1 score and the Kolmogorov–Smirnov test. Results: A total of 4015 continuous glucose‐monitoring data points from 440 patients were included, and 28 variables were selected to build the risk prediction model. The 440 patients had an average age of 62.7 years. Approximately 48.2% of the patients were female and 51.8% were male. Nocturnal hypoglycaemia appeared in 573 (14.30%) of 4015 continuous glucose monitoring data. The light gradient boosting machine model demonstrated the highest predictive performances: AUC (0.869), specificity (0.802), accuracy (0.801), precision (0.409), recall rate (0.797), F1 score (0.255) and Kolmogorov (0.603). The selected predictive factors included time below the target glucose range, duration of diabetes, insulin use before bed and dynamic blood glucose monitoring parameters from the previous day. Patient or Public Contribution: No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular disease (CVD) risk, but whether T2DM directly causes adverse cardiac remodelling is uncertain. We performed a comprehensive Mendelian randomization (MR) analysis to investigate the causal relevance of T2DM to CVD outcomes and cardiac structure/function. Methods and results: Bidirectional two‐sample MR was conducted using summary‐level data from European‐ancestry genome‐wide association studies. The T2DM GWAS data included 80 154 cases and 853 816 controls from the DIAGRAM consortium. Outcomes included coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure, atrial fibrillation, and various quantitative cardiac imaging traits assessed by magnetic resonance imaging. MR analysis revealed causal associations between genetic predisposition to T2DM and increased risk of CAD (odds ratio [OR] 1.104, 95% confidence interval [CI] 1.078–1.130, P = 2.59e‐16), MI (OR 1.129, 95% CI 1.094–1.166, P = 6.02e‐14) and stroke (OR 1.086, 95% CI 1.064–1.109, P = 1.02e‐14). These associations were validated in the FinnGen cohort (CAD: OR 1.117, 95% CI 1.075–1.158, P = 1.56e‐9; MI: OR 1.132, 95% CI 1.083–1.184, P = 4.27e‐8; stroke: OR 1.138, 95% CI 1.107–1.170, P = 3.52e‐20). Multivariable MR show consistent findings (CAD: OR 1.063, 95% CI 1.031–1.097, P = 1.11e‐4; MI: OR 1.088, 95% CI 1.042–1.135, P = 1.12e‐4; stroke: OR 1.066, 95% CI 1.032–1.101, P = 1.18e‐4) after adjusting for cardiometabolic traits. T2DM was causally associated with higher left ventricular mass index (β = 0.473, 95% CI 0.193 to 0.752, P = 0.001), lower indexed right atrial minimum (β = −0.048, 95% CI −0.073 to −0.022, P = 2.1e‐5), and maximum (β = −0.042, 95% CI −0.065 to −0.019, P = 4.12e‐5) areas. The effects on right atrial size remained significant after adjusting for risk factors (minimum area: β = −0.041, 95% CI −0.072 to −0.010, P = 0.009; maximum area: β = −0.039, 95% CI −0.069 to −0.008, P = 0.012). Both apolipoprotein A1 and SBP are important mediators in the causal relationship between T2DM and left ventricular mass index. No reverse causal associations were identified. Conclusions: Our MR study demonstrates that genetic liability to T2DM plays causal roles in CAD, MI, stroke, and cardiac structure changes including left ventricular hypertrophy and reduced right atrial dimensions. These findings provide genetic evidence supporting glycaemic control in T2DM to mitigate cardiovascular complications and adverse cardiac remodelling. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusion Tirzepatide, a dual agonist of glucagon‐like peptide receptor and glucose‐dependent insulinotropic polypeptide receptor, is expected to exhibit high clinical efficacy in obese type 2 diabetic patients. We evaluated the effects of tirzepatide on pancreatic β‐cells and the liver, an insulin‐target organ, in a mouse model of obese type 2 diabetes mellitus.Obese type 2 diabetic db/db mice (BKS.Cg−/+ Leprdb/+ Leprdb/Jcl*) were used in this study. Starting at 7 weeks of age, mice were treated with tirzepatide (30 nmol/kg, subcutaneous injection twice a week) or semaglutide (200 nmol/kg, subcutaneous injection twice a week). The control group received phosphate‐buffered saline (40–50 μL/subcutaneous injection twice a week). After 4 weeks of drug administration, pancreatic β‐cells and the liver were removed and examined.Compared to the control group, blood glucose and body weight were significantly reduced in the group that received either tirzepatide or semaglutide (p < 0.001 and p < 0.05, respectively). Fasting insulin was significantly higher in the semaglutide and tirzepatide groups compared to the control group (p < 0.001). β‐Cell mass and quality of insulin granules in β‐cells similarly increased in the semaglutide and tirzepatide groups compared to the control group (p < 0.05 and p < 0.001, respectively). The fat staining area in the liver in oil red O staining and the liver–spleen ratio in computed tomography showed improvement only in the tirzepatide group (p < 0.001 and p < 0.005, respectively). Liver macrophage M1/M2 ratio similarly improved with semaglutide and tirzepatide (p < 0.05).Tirzepatide and semaglutide exhibited similar potent glucose‐lowering effects. At concentrations used in the present experiments, tirzepatide exhibited more beneficial effects on β‐cell‐related gene expression, insulin granule count and glucose‐stimulated insulin secretion compared to semaglutide. In addition, tirzepatide exhibited a stronger favourable effect on hepatic fat deposition and improved inflammation in the liver. This is the first report showing that tirzepatide, a novel diabetes drug, exhibits a superior effect on pancreatic β‐cells and the liver of obese type 2 diabetic mice. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusion The prevalence of the coexistence of low muscle mass and obesity is increasing, particularly with a rising trend observed in patients diagnosed with type 2 diabetes mellitus (T2DM). However, the association between the coexistence of low muscle mass and obesity and diabetic complications remains unclear. This study aimed to investigate these associations in patients with T2D.A retrospective study was conducted, including 2387 hospitalized patients with T2DM. Data on demographic characteristics, biochemical parameters, diabetic complications and body composition was from electronic health records. The participants were categorized as control, low muscle mass, obesity and the coexistence of the low muscle mass and obesity groups according to the body compositions evaluated by dual‐energy X‐ray absorptiometry. Multiple logistic regression models were applied to assess the associations between the pattern of body composition and complications of diabetes.After adjustment for potential confounders, compared with patients in the control group, the odds ratios [95% confidence intervals (CIs)] of macrovascular complications of diabetes were 0.62 (95% CI, 0.27–1.39) for those in the low muscle mass group, 1.12 (95% CI, 0.59–2.11) in the obesity group, and 2.43 (95% CI, 1.16–5.07) in the coexistence of the low muscle mass and obesity group, respectively; the odds ratios (95% CIs) of microvascular complications of diabetes were 0.86 (95% CI, 0.52–1.43) for those in the low muscle mass group, 0.82 (95% CI, 0.53–1.26) in the obesity group, and 1.21 (95% CI, 0.69–2.15) in the coexistence of the low muscle mass and obesity group, respectively.According to our findings, the coexistence of low muscle mass and obesity, rather than low muscle mass or obesity alone, was significantly associated with a higher prevalence of macrovascular complications in hospitalized patients with T2DM. This association was not observed for diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Methods Results Conclusions To assess the risk of difference between 2 h post‐load plasma glucose (2 h‐PG) and fasting plasma glucose (FPG) on incident prediabetes/type 2 diabetes (T2DM) among normoglycemic individuals.Among 4,971 individuals aged ≥20 years, the associations of the difference between 2 h‐PG and FPG with outcomes were examined using multivariable‐adjusted Cox regression analysis. Participants were categorized into three groups: a low post‐load group (2 h‐PG ≤ FPG, as the reference group); a high post‐load group (2 h‐PG > FPG and ≥75th percentile of the difference); and a medium post‐load group (2 h‐PG > FPG and <75th percentile of the difference), which was further categorized into three groups by equal ranges.Over a median of 11.5 years of follow‐up, 2,331 new cases of prediabetes/type 2 diabetes and 360 cases of type 2 diabetes occurred. Greater risks of incident prediabetes/type 2 diabetes in second (9–16 mg/dL) and third (17–24 mg/dL) medium post‐load, as well as high post‐load (≥25 mg/dL) categories, were found, with hazard ratios (95% confidence intervals) of 1.26 (1.11–1.44), 1.32 (1.15–1.51), and 1.69 (1.51–1.90), respectively; the issue was more prominent among women (P for interaction = 0.005). The risk of incident type 2 diabetes was also higher for these categories. After further adjustment for the homeostasis model assessment of insulin resistance, result remained essentially unchanged. Even among individuals with low normal FPG (i.e., <90 mg/dL), ≥9 mg/dL difference between 2 h‐PG and FPG increased the risk of composite prediabetes/ type 2 diabetes.Greater levels of 2 h‐PG as low as 9 mg/dL than FPG among normoglycemic individuals is a harbinger of prediabetes/type 2 diabetes development. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Early post‐transplant hyperglycaemia (EPTH) and post‐transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5‐year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre‐transplant T2DM with adverse transplant‐related outcomes.Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia.A total of 141 patients were included, of whom 25 had pre‐existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre‐existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5‐year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre‐existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three‐fold increased likelihood of death compared to patients that remained free from diabetes.EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre‐existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5‐year survival compared to patients who remained free from diabetes during follow‐up. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions The 2023 Delphi consensus recommended the use of new term, metabolic dysfunction‐associated steatotic liver disease (MASLD), aiming conceptual shift from the conventional non‐alcoholic fatty liver disease (NAFLD). The association between NAFLD and type 2 diabetes mellitus (T2DM) development is well known. This study aimed to examine the correlation between MASLD and T2DM development, comparing their utility as predictors.This retrospective cohort study obtained data from a medical health checkup program conducted at Asahi University Hospital, Japan, between 2004 and 2021. Logistic regression analysis was used to assess the association between MASLD and incident T2DM over 5 years. To compare the predictive utility of NAFLD and MASLD, receiver operating characteristic curves were drawn, followed by area under the curve (AUC) comparisons.In total, 15,039 participants (59.6% males; median [interquartile range {IQR}] age, 44 [38, 50] years) were included. Out of 2,682 participants meeting the criteria for MASLD, 234 individuals (8.7%) developed T2DM. Multivariate analysis revealed a significantly elevated risk of T2DM in MASLD compared with the reference healthy group (without steatotic liver disease or cardiometabolic risk), presenting an OR of 127.00 (95% CI 40.40–399.00, P < 0.001). The concordance rate of diagnosis between NAFLD and MASLD was 98.7%. The AUC values were 0.799 for NAFLD and 0.807 for MASLD, respectively. Comparative analysis of the AUC showed a statistical difference between NAFLD and MASLD (P < 0.001).MASLD was shown to be a significant risk factor for incident T2DM, exhibiting a potentially higher predictive capacity than conventional NAFLD. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions To conduct a systematic review in order to better understand the association of glycaemic risk factors and diabetes duration with risk of heart failure (HF) in individuals with type 2 diabetes (T2D).We identified longitudinal studies investigating the association of glycaemic factors (glycated haemoglobin [HbA1c], HbA1c variability, and hypoglycaemia) and diabetes duration with HF in individuals with T2D. Hazard ratios and odds ratios were extracted and meta‐analysed using a random‐effects model where appropriate. Risk of bias assessment was carried out using a modified Newcastle–Ottawa Scale. Egger's test along with the trim‐and‐fill method were used to assess and account for publication bias.Forty studies representing 4 102 589 people met the inclusion criteria. The risk of developing HF significantly increased by 15% for each percentage point increase in HbA1c, by 2% for each additional year of diabetes duration, and by 43% for having a history of severe hypoglycaemia. Additionally, variability in HbA1c levels was associated with a 20%–26% increased risk of HF for each unit increase in the metrics of variability (HbA1c standard deviation, coefficient of variation, and average successive variability). All included studies scored high in the risk of bias assessment. Egger's test suggested publication bias, with trim‐and‐fill analyses revealing a significant 14% increased risk of HF per percentage point increase in HbA1c.Glycaemic risk factors and diabetes duration significantly contribute to the heightened risk of HF among individuals with T2D. A reduction in risk of HF is anticipated with better management of glycaemic risk factors. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Abnormalities in specific echocardiographic parameters and cardiac biomarkers have been reported among individuals with diabetes. However, a comprehensive characterization of diabetic cardiomyopathy (DbCM), a subclinical stage of myocardial abnormalities that precede the development of clinical heart failure (HF), is lacking. In this study, we developed and validated a machine learning‐based clustering approach to identify the high‐risk DbCM phenotype based on echocardiographic and cardiac biomarker parameters.Among individuals with diabetes from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of cardiovascular disease and other potential aetiologies of cardiomyopathy (training, n = 1199), unsupervised hierarchical clustering was performed using echocardiographic parameters and cardiac biomarkers of neurohormonal stress and chronic myocardial injury (total 25 variables). The high‐risk DbCM phenotype was identified based on the incidence of HF on follow‐up. A deep neural network (DeepNN) classifier was developed to predict DbCM in the ARIC training cohort and validated in an external community‐based cohort (Cardiovascular Health Study [CHS]; n = 802) and an electronic health record (EHR) cohort (n = 5071). Clustering identified three phenogroups in the derivation cohort. Phenogroup‐3 (n = 324, 27% of the cohort) had significantly higher 5‐year HF incidence than other phenogroups (12.1% vs. 4.6% [phenogroup 2] vs. 3.1% [phenogroup 1]) and was identified as the high‐risk DbCM phenotype. The key echocardiographic predictors of high‐risk DbCM phenotype were higher NT‐proBNP levels, increased left ventricular mass and left atrial size, and worse diastolic function. In the CHS and University of Texas (UT) Southwestern EHR validation cohorts, the DeepNN classifier identified 16% and 29% of participants with DbCM, respectively. Participants with (vs. without) high‐risk DbCM phenotype in the external validation cohorts had a significantly higher incidence of HF (hazard ratio [95% confidence interval] 1.61 [1.18–2.19] in CHS and 1.34 [1.08–1.65] in the UT Southwestern EHR cohort).Machine learning‐based techniques may identify 16% to 29% of individuals with diabetes as having a high‐risk DbCM phenotype who may benefit from more aggressive implementation of HF preventive strategies. [ABSTRACT FROM AUTHOR]

Introduction Methods Ethics and Dissemination Trial Registration Structured diabetes self‐management education (DSME) is internationally recommended for people with type 2 diabetes to support self‐management and to prevent associated long‐term complications. ‘Attendance’ at DSME is currently benchmarked as having completed a registration form and at least one active engagement with programme content, and ‘completion’ measured against ≥60% completion, despite landmark trials reporting outcomes based on the full completion of a programme. Little is known about the effectiveness of DSME on the psychological and emotional health of people with diabetes who complete less than the full DSME programme. We report a protocol for a single‐centre randomised feasibility study to assess the impact of differing completion rates of a face‐to‐face DSME programme on patient reported outcomes of self‐care, diabetes distress and quality of life in people with type 2 diabetes.A randomised feasibility study in 120 people with type 2 diabetes due to attend a secondary care diabetes clinic in the North West UK for DSME. Participants will be randomised into one of the four groups: Group 1 full DSME programme, Group 2 60%, Group 3 10% and Group 4 0% (delayed education). Psychometric questionnaire scores will be evaluated at baseline and 3–4 months post‐intervention. Measures of feasibility (eligibility, recruitment and retention rates) will be reported.The DIABETES‐PRO study was approved by the London–Surrey Borders Research Ethics Committee (24/LO/0235). Results will be shared with study participants and published in peer‐reviewed journals.Clinicaltrials.gov NCT06419907. [ABSTRACT FROM AUTHOR]

Background: This study aimed to test the efficacy of patient‐centered self‐management intervention (PACE‐SMI) to improve HbA1c, self‐efficacy, and self‐care behaviors in adults with type 2 diabetes mellitus (T2DM). Methods: In this multicenter, parallel two‐arm randomized controlled trial, 612 adults with T2DM and HbA1c ≥ 7% were enrolled and assigned to the control group (n = 310) and the intervention group (n = 302) using stratified permuted block randomization. The control group received usual care, whereas the intervention group received usual care plus nurse‐led, theory‐driven, culturally tailored PACE‐SMI, comprising eight weekly sessions of individualized education, counseling, behavioral training, and home visit. Outcomes were assessed at baseline, postintervention, and 3 months follow‐up. Results: Data at 3 months were provided by 583 participants (control: n = 295, intervention: n = 288). Per‐protocol analysis showed that the intervention group had a lower mean HbA1c (8.49% [standard deviation (SD), 1.58]) than the control group (8.74% [SD, 1.62]), with small yet statistically significant mean difference of 0.25% (95% confidence interval [CI], −0.01 to 0.51; Cohen's d = 0.16; p = 0.03). Self‐efficacy and self‐care behaviors significantly improved in the intervention group (116.89 [SD, 25.50] and 70.01 [SD, 17.97]) compared to the control group (75.43 [SD, 18.99] and 51.54 [SD, 12.04]), with mean differences of 41.48 (95% CI, 37.83–45.13; Cohen's d = 1.84; p < 0.0001) and 18.56 (95% CI, 16.08–21.04; Cohen's d = 1.22; p < 0.0001), respectively. Linear regression analysis indicated the effect of PACE‐SMI on HbA1c was significantly mediated by improvements in self‐efficacy and self‐care behaviors (R2 = 0.232, p < 0.001). Conclusion: PACE‐SMI led to modest but significant improvement in HbA1c and substantial enhancements in self‐efficacy and self‐care behaviors in adults with T2DM. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Dulaglutide is a relatively unpopular GLP‐1 receptor agonist used for weight loss. This case demonstrates that dulaglutide may be beneficial for weight loss in morbidly obese patients with multiple comorbidities after thoroughly evaluating its efficacy, benefits, and long‐term adverse effects through clinical trials. We present a case of a 27‐year‐old ex‐sumo wrestler with bipolar II disorder, morbid obesity, hypertension, Type 2 Diabetes Mellitus (DM), and a Body Mass Index (BMI) of 49.66 kg/m2. He was non‐compliant with lifestyle modifications and resistant to conventional treatments, including metformin, and was also using multiple antipsychotic drugs. After introducing dulaglutide, he achieved a 40 kg (−21%) weight loss and a BMI reduction of 10.3 kg/m2 over 6 months, with no side effects and improved glycemic control, demonstrating dulaglutide's efficacy for weight loss in such challenging presentations. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus and overweight/obesity increase healthcare costs. Both are also associated with accelerated aging. However, the contributions of this accelerated aging to increased healthcare costs are unknown. Methods: We use data from a 8‐year longitudinal cohort followed at 16 U.S. clinical research sites. Participants were adults aged 45–76 years with established type 2 diabetes and overweight or obesity who had enrolled in the Action for Health in Diabetes clinical trial. They were randomly (1:1) assigned to either an intensive lifestyle intervention focused on weight loss versus a comparator of diabetes support and education. A validated deficit accumulation frailty index (FI) was used to characterize biological aging. Discounted annual healthcare costs were estimated using national databases in 2012 dollars. Descriptive characteristics were collected by trained and certified staff. Results: Compared with participants in the lowest tertile (least frail) of baseline FI, those in the highest tertile (most frail) at Year 1 averaged $714 (42%) higher medication costs, $244 (22%) higher outpatient costs, and $800 (134%) higher hospitalization costs (p < 0.001). At Years 4 and 8, relatively greater increases in FI (third vs. first tertile) were associated with an approximate doubling of total healthcare costs (p < 0.001). Mean (95% confidence interval) relative annual savings in healthcare costs associated with randomization to the intensive lifestyle intervention were $437 ($195, $579) per year during Years 1–4 and $461 ($232, $690) per year during Years 1–8. These were attenuated and the 95% confidence interval no longer excluded $0 after adjustment for the annual FI differences from baseline. Conclusions: Deficit accumulation frailty tracks well with healthcare costs among adults with type 2 diabetes and overweight or obesity. It may serve as a useful marker to project healthcare needs and as an intermediate outcome in clinical trials. [ABSTRACT FROM AUTHOR]

Aims: The aim of this work is to compare empagliflozin systemic exposure between patients with heart failure (HF) and patients with type 2 diabetes (T2D). Methods: Analysis of covariance (ANCOVA) compared steady state trough concentrations of empagliflozin 10 mg in EMPEROR‐reduced (patients with HF with reduced ejection fraction [HFrEF]) and EMPA‐REG OUTCOME (patients with T2D at high cardiovascular risk) after adjusting for eGFR and body weight. Results: The difference in geometric Mean (gMean) empagliflozin steady state trough concentration of 10 mg empagliflozin between EMPEROR‐reduced and EMPA‐REG OUTCOME was 1.47‐fold (95% confidence interval [CI]: 1.33, 1.63). Additionally, ANCOVA for the sub‐group of patients with both T2D and HF conditions revealed a difference in gMean steady state trough concentration of 1.53‐fold (95% CI: 1.26, 1.85). In both patients with HFrEF and HF with preserved EF (HFpEF), there was no major difference in empagliflozin steady state trough exposure by New York Heart Association (NYHA) classification or by use of angiotensin receptor‐neprilysin inhibitor as comedication. A weak positive correlation was observed for NT‐proBNP at Week 12 and empagliflozin steady state trough concentration in both patients with HFrEF and HFpEF (Pearson correlation r = 0.19). Conclusions: Plasma concentrations of empagliflozin in patients with HF were higher compared to patients with T2D, but the exposure resulting from the 10 mg dose was still below the exposure resulting from the dose of 25 mg approved in patients with T2D. The difference in exposure was attributable to demographic characteristics and HF‐induced pathophysiological changes. Overall, the results confirm 10 mg as the appropriate empagliflozin dose in patients with HF. [ABSTRACT FROM AUTHOR]

Aim: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long‐term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Methods: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end‐stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. Results: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%–30% decrease, 14.4% (n = 1199) experienced a 0%–30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin‐to‐creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: −3.6 ± 10.9, −2.0 ± 9.5, −1.1 ± 8.6, and −0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61–4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48–0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. Conclusion: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long‐term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To investigate the effect of patient characteristics on imeglimin effectiveness in Japanese patients with type 2 diabetes mellitus. Materials and Methods: Data were pooled from two randomized, placebo‐controlled, 24‐week, double‐blind studies of imeglimin monotherapy in Japanese adults with type 2 diabetes mellitus, with the proportion of responders (glycated hemoglobin [HbA1c] < 7.0%) and sustained responders (i.e., achieved and maintained response) in the imeglimin 1,000 mg twice daily group calculated at each visit. Patient factors significantly (P < 0.05) correlated with response were explored through multivariate logistic regression. Subgroup analyses compared the efficacy of imeglimin in patients with a HbA1c improvement less than or equal to −0.3% (early responders) versus greater than −0.3% (early non‐responders) at week 4. Results: A total of 38.0% of imeglimin‐treated patients and 7.2% of placebo‐treated patients were responders (P < 0.001, number needed to treat = 4). The proportion of sustained responders at weeks 4, 8, 12, 16 and 20 was 10.6, 19.0, 24.0, 25.7 and 29.1%, respectively (>70% of responders at each visit). Improvements in HbA1c and fasting glucose were significantly greater in early responders versus early non‐responders from week 4; between‐group differences remained significant to week 24. Older age (odds ratio 1.09, 95% confidence interval 1.04–1.14; P < 0.001); treatment‐naïve status vs previous treatment (odds ratio 3.70, 95% confidence interval 1.55–8.82; P = 0.003), and lower baseline HbA1c (odds ratio 0.06, 95% confidence interval 0.02–0.16; P < 0.001) predicted response. Conclusions: A significantly higher proportion of patients receiving imeglimin 1,000 mg twice daily monotherapy were responders versus placebo. Most (>70%) were sustained responders, suggesting that response is fairly predictable. Older age, treatment‐naïve status and early treatment response significantly predicted imeglimin effectiveness. [ABSTRACT FROM AUTHOR]

Objective: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). Design, Patients and Measurements: This retrospective single‐centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut‐off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. Results: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p =.001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = −.117, r = −.131, r =.117, p <.001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p <.001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76–7.52, p =.001). Conclusion: Albuminuria is more frequently observed in patients with hypomagnesemia. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) is responsible for advanced glycation end‐product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography–mass spectrometry (GC–MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC–MS. Validated GC–MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM. Highlights: MG is a determinant of carbonyl stress in T2DM patients.The substrates of MG were analysed by GC–MS in T2DM with and without ACS.The validated GC–MS methods were sensitive, accurate, precise and reliable.Plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol are associated with ACS risk in T2DM. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd‐exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd‐exposed rats had increased liver cholesterol levels, insulin receptor beta (IRβ) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats. [ABSTRACT FROM AUTHOR]

Our meta‐analysis aimed to quantify the association between Hidradenitis suppurativa (HS) and several risk factors including obesity, smoking, and type 2 diabetes mellitus (T2DM). We searched PubMed, Scopus, Embase, Web of Science, and cumulative index to nursing and allied health literature for articles reporting either the odds ratio (OR) or the numbers of HS cases associated with obesity, smoking, or T2DM, and including HS negative controls. Risk of bias was assessed against the risk of bias in non‐randomized studies of interventions tool. Data synthesis was done using the random effects model with heterogeneity being evaluated with I2 statistic. Twenty‐three studies with a total of 29 562 087 patients (average age of 36.6 years) were included. Ten studies relied on country‐level data, while six studies collected their data from HS clinics. The analysis showed a significant association between HS and female sex (OR 2.34, 95% CI 1.89–2.90, I2 = 98.6%), DM (OR 2.78, 95% CI 2.23–3.47, I2 = 98.9%), obesity (OR 2.48, 95% CI 1.64–3.74, I2 = 99.9%), and smoking (OR 3.10 95% CI 2.60–3.69, I2 = 97.1%). Our meta‐analysis highlights HS links to sex, DM, obesity, and smoking, with emphasis on holistic management approach. Further research is needed on molecular mechanisms and additional risk factors for improved patient care. [ABSTRACT FROM AUTHOR]

Background: The response of patients with Type 2 diabetes mellitus (T2DM) to metformin may be a variation because of genetic differences in solute carrier (SLC) transporter proteins and other effect factors, which have an important effect on how metformin is processed in the body and its efficiency for glycaemic control. Aim: This study was conducted to investigate the impact of certain genetic variants of the organic cation transporter genes OCT3 (SLC22A3 rs12194182 and rs8187722) and MATE2 (SLC47A2 rs12943590) and their association with glycaemic parameters in patients with T2DM who respond poorly to metformin. Patients and Methods: This cross‐sectional study involved 150 Iraqi cases with T2DM who were prescribed a daily dose of (1000 mg/day) metformin for a minimum of 3 months. Various parameters included are as follows: demographic data, glycaemic parameters and three SNPs: rs12943590 variant of SLC47A2, rs12194182 and rs8187722 variant of SLC22A3 using the standard PCR‐sequencing technique. Results: Thirty‐nine patients (26.17%) were responders, whereas 111 patients (73.82%) could not respond to metformin treatment. Upon analysing the genotypes of the rs12943590 variants of SLC47A2, rs12194182 and rs8187722 SNPs of SLC22A3, the present findings revealed a nonsignificant association of genetic variations in all SNPs with metformin response. SLC47A2 (rs12943590) showed nonsignificant associations of the GG, AA and AG genotyping; SLC22A3 (rs12194182) showed nonsignificant associations of the TT, TC and CC genotyping; and SLC22A3 (rs8187722) showed nonsignificant associations of the AA, CC and AC genotyping between two groups. Conclusion: Variations in genes SLC22A3 and SLC47A2 did not have a significant role in the response of patients with T2DM to metformin (1000 mg/day). [ABSTRACT FROM AUTHOR]

Aims: To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This cross‐sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular‐kidney‐metabolic (CKM) syndrome stage. Side‐stream dark‐field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine‐learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points. Results: Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima–media thickness (IMT), brachial‐ankle pulse wave velocity (ba‐PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut‐off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA. Conclusions: Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Physical activity is an important behaviour for managing the ten times increased risk of type 2 diabetes after gestational diabetes. Previous studies exploring physical activity promotion in healthcare focus on general practitioners but have not explored the gestational diabetes pathway. Therefore, this paper explores the barriers to and suggestions for, activity promotion along the gestational diabetes healthcare pathway.The paper was written in accordance with the Standards for Reporting Qualitative Research. Patient and Public Involvement with women who had lived experiences of gestational diabetes informed purposeful sampling by identifying which healthcare professional roles should be targeted in participant recruitment. Participants were recruited through word‐of‐mouth, that is, email and connections with local healthcare service leads. Twelve participants took part in semi‐structured one‐to‐one interviews, analysed using reflexive thematic analysis.Participants included a Public Health Midwife (n = 1), Diabetes Midwifes (n = 3), Diabetes Dietitian (n = 1), Diabetes Consultants (n = 2), Diabetes Specialist Nurse (n = 1), general practitioners (n = 2), Practice nurse (n = 1) and a Dietitian from the UK National Diabetes Prevention Program (n = 1). Six themes were generated: ‘management of gestational diabetes takes precedent’, ‘poor continuity of care’, ‘lack of capacity to promote PA’, ‘beliefs about the acceptability of PA promotion’, ‘resources to support conversations about PA’ and ‘adapting healthcare services for women post‐gestational diabetes’.During pregnancy messaging around physical activity is consistent, yet this is specific for managing gestational diabetes and is not followed through postnatally. Improvements in continuity of care are necessary, in addition to ensuring the availability and links with wider exercise and activity schemes. [ABSTRACT FROM AUTHOR]

Background Methods Results Discussion Registration To assess the efficiency of periodontal treatment (PT) in improving diabetes‐related outcomes in adults with type 2 diabetes mellitus (T2DM) and periodontitis, providing an updated and comprehensive synthesis from economic evaluations (EE).Seven databases and one register were independently searched by two reviewers for articles published up to 8 May 2024. Studies that assessed the efficiency of PT versus no treatment or other dental treatments were included. Risk of bias was assessed using the Cochrane RoB 2, ROBINS‐I and ECOBIAS tools for the first stage of EE and the CHEERS checklist and NICE quality appraisal tool for overall EE. Qualitative and quantitative syntheses of the articles were conducted and assessed using the GRADE approach.Eleven studies were included. PT reduces total healthcare costs, including inpatient and outpatient, diabetes‐related costs and other drug costs (low to moderate certainty). A total incremental net benefit of USD 12 348 (2022 currency, 95% CI 12 195–12 500) was estimated from three high‐quality model‐based cost‐utility analyses (high certainty).The inclusion of PT in the comprehensive treatment of patients with T2DM and periodontitis is cost‐effective. Future research is required to ensure the transferability of these findings and inform decision makers from different countries.PROSPERO CRD42023443146. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the mechanism by which irisin affects β‐cell pyroptosis in type 2 diabetes mellitus (T2DM). The in vivo T2DM model was established by raised with high‐fat diet and intraperitoneally injection of streptozocin. Min6 cells were divided into four groups: negative control (NC), high glucose (HG), HG + irisin, and HG + irisin+3‐MA. The cell viability was determined by CCK‐8 assay. Dual‐luciferase gene reporter assay was conducted to confirm the binding between miR‐19b‐3p and SOCS3. The expression level of FNDC5 and GSDMD was visualized using the immunofluorescence assay. The protein level of FNDC5, Beclin1, LC3II/I, NLRP3, cleaved‐caspase‐1, GSDMD‐N, STAT3, p‐STAT3, and SOCS3 was determined by Western blotting. The secretion of irisin, lactate dehydrogenase (LDH), and insulin was checked by ELISA. In vivo results showed that pathological changes in islet tissues with declined number of β cells, elevated FBG value, decreased FIN and HOMA‐β value, elevated autophagy‐associated proteins expressions, and activated NLRP3 signaling in T2DM mice, which were dramatically reversed by FNDC5 overexpression. Furthermore, the declined level of miR‐19b‐3p and p‐STAT3, as well as the upregulation of SOCS3, was greatly rescued by FNDC5 overexpression. The in vitro data confirmed the binding site between SOCS3 and miR‐19b‐3p. SOCS3 was downregulated and p‐STAT3 was upregulated in miR‐19b‐3p mimic‐treated Min6 cells. In HG‐stimulated Min6 cells, the elevated cell viability, increased production of insulin, decreased release of LDH, and inactivated NLRP3 signaling induced by irisin were abolished by miR‐19b‐3p inhibitor and STAT3 inhibitor. The increased level of autophagy‐related proteins and activated SOCS3/STAT3 axis induced by irisin in HG‐stimulated Min6 cells were abolished by miR‐19b‐3p inhibitor. The inhibitory effect of irisin against NLRP3 signaling in HG‐stimulated Min6 cells was abrogated by 3‐MA. In conclusion, irisin alleviated the pyroptosis of β cells in T2DM by inhibiting NLRP3 signaling through miR‐19b‐3p/SOCS3/STAT3 axis mediated autophagy. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM‐related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high‐fat diet combined with a single streptozotocin injection in 7‐week‐old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end‐products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE‐RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM. [ABSTRACT FROM AUTHOR]

Aim: To date, there are limited clinical studies and real‐world evidence investigating whether sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase‐4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials and Methods: This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time‐course changes in the FLI values were also assessed. Results: This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18‐1.38), 1.24 (95% CI 1.13‐1.37) and 1.19 (95% CI 1.05‐1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow‐up period. Conclusion: SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head‐to‐head comparisons from clinical studies, our study, using real‐world data, may support physicians' decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pityriasis versicolor (PV), a cutaneous fungal infection, most commonly affects adolescents and young adults and is associated with hyperhidrosis and humid weather. Understanding other factors associated with PV might help improve diagnostic and treatment practices. Objectives: PV's associations with patient demographics, comorbidities and medication exposures were assessed using the All of Us Database, a large, diverse, national database from the United States. Methods: A case–control study with multivariable analysis was performed. Results: We identified 456 PV case‐patients and 1368 control‐patients. PV case‐patients (vs. control‐patients) were younger (median age [years] (standard deviation): 48.7 (15.4) vs. 61.9 (15.5); OR: 0.95, CI: 0.94–0.96) and more likely to be men versus women (42.8% vs. 33.9%, OR: 1.45, CI: 1.16–1.79) and Black (19.5% vs. 15.8%, OR: 1.35, 95% CI: 1.02–1.80) or Asian (4.6% vs. 2.7%, OR: 1.86, CI: 1.07–3.24) versus White. PV case‐patients more frequently had acne (5.3% vs. ≤1.5%, OR: 5.37, CI: 2.76–10.48) and less frequently had type 2 diabetes mellitus (T2DM) (14.7% vs. 24.7%, OR: 0.52, CI: 0.39–0.70) and hypothyroidism (OR: 10.3% vs. 16.4%, OR: 0.59, CI: 0.42–0.82). In multivariable analysis, PV odds were significantly higher in those with acne and lower in those with T2DM, older age and female sex. Conclusions: Our results may be used as a basis for future studies evaluating whether acne treatment may decrease PV risk. Physicians could educate patients with acne about PV, including strategies to control modifiable PV risk factors, such as avoidance of hot and humid environments and avoidance of use of topical skin oils. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. Materials and Methods: The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet β‐cell function, insulin resistance and comprehensive management measures. Results: Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0–4.0 years). The baseline HbA1c was 11.2% (IQR 9.2–12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3–6.1%]) in the half‐year course group and the highest in the 4‐year course group (9.0 [IQR 6.8%–11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of β‐cell function, and a lower proportion with a controlled diet, moderate‐intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of β‐cell function at follow up, continuous moderate‐intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control. Conclusions: Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet β‐cell function. A good lifestyle, especially moderate‐intensity exercise, can help such cases better control their blood glucose level. [ABSTRACT FROM AUTHOR]

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel‐group, open‐label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty‐two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long‐term safety profile and efficacy have not been specifically studied in this population. [ABSTRACT FROM AUTHOR]

Background: Beta 2‐microglobulin (β2‐MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2‐MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2‐MG and LVH in T2DM patients. Methods: The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non‐LVH groups based on echocardiography results. Serum β2‐MG levels were measured, and participants were categorized into four groups (Q1–Q4) by their serum β2‐MG quartile. The relationship of serum β2‐MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. Results: The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2‐MG level corresponded to a 1.17‐fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05–1.31); p = 0.006]. When considering β2‐MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09–1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36–2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between β2‐MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of β2‐MG for LVH in T2DM patients. Conclusion: Elevated serum β2‐MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development. [ABSTRACT FROM AUTHOR]