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Showing 80 of 2625 matching items (19450 indexed).
Nature
Nature, Published online: 03 September 2026; doi:10.1038/d41586-026-02781-1 Mice on GLP-1s also performed better on cognitive tasks than those on a calorie restricted diet . Plus, satellite images showed early warning signs of glacier collapse near the Nepal–Tibet border and the impact of people saying fewer words aloud.
Diabetes · ADA
We investigated whether ketogenesis is required for the metabolic benefits of intermittent fasting (IF) and whether these effects differ between sexes. We specifically asked whether ketogenesis drives IF-mediated protection against obesity and fatty liver disease in male and female mice. We found that IF reduced adiposity independently of ketogenesis in both sexes, but its antisteatotic and antifibrotic effects were ketogenesis-dependent in male mice and minimal in female mice. These findings reveal a sex-dependent ketogenesis-inflammation-fibrosis axis and highlight the need to consider sex and ketone metabolism when designing dietary or therapeutic interventions.
Diabetes care · ADA
Developing a path forward for sodium-glucose cotransporter (SGLT) inhibitor treatment for heart and kidney disease in people with type 1 diabetes (T1D) is essential. This article offers the perspective of experts from the fields of endocrinology, nephrology, and cardiology on available data for the efficacy and safety of SGLT inhibitors in T1D, how the far more extensive data from people with type 2 diabetes (T2D) and people without diabetes would be expected to translate to T1D, and what steps are required to advance toward regulatory approvals and clinical uptake of SGLT inhibitors in T1D for heart and kidney disease. Our conclusion is that the mechanisms driving efficacy of SGLT inhibitors for heart and kidney disease in T2D and nondiabetic disease are likely applicable to T1D and that in light of the data supporting efficacy in these populations, registrational trials in T1D might not require powering for traditional event-based outcomes and investigators may instead rely on suitable surrogate end points, allowing for more feasible trials. Investigators in these trials must also carefully collect data associated with diabetic ketoacidosis (DKA), the critical risk of SGLT inhibitor use in T1D. DKA risk mitigation is essential for SGLT inhibitor use in T1D; protocols to mitigate risk have been developed, but rigorous data on their effectiveness are lacking. We describe a roadmap to advance SGLT inhibitors for T1D heart and kidney disease, which includes the use of feasible trial designs based on surrogate end points and rigorous safety protocols to minimize DKA events.
Nature
Nature, Published online: 02 September 2026; doi:10.1038/d41586-026-02757-1 Older female mice given an anti-obesity medication lived longer and in better health than did mice not taking one.
Diabetes care · ADA
OBJECTIVE: To compare the risk of motility-related gastrointestinal (GI) events associated with commonly prescribed opioids among adults with type 2 diabetes (T2D) prescribed glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, a population in whom the GI safety of concomitant opioid use has not been well characterized. RESEARCH DESIGN AND METHODS: A population-based, new-user cohort study was conducted using U.S. insurance claims (2016-2025) among adults with T2D prescribed GLP-1RA therapy who initiated use of oxycodone, hydrocodone, or tramadol. We evaluated a composite of motility-related GI events, including severe constipation, bowel obstruction, and gastroparesis, and estimated 30-day weighted absolute risks, risk ratios (RRs), and risk differences (RDs) using propensity score-matching weights. RESULTS: Among 411,188 patients (mean age 62.8 years; 53.8% female) with T2D and using a GLP-1RA, 24.4% initiated use of oxycodone, 48.5% hydrocodone, and 27.1% tramadol. The weighted 30-day absolute risk of motility-related GI events was 0.51% for oxycodone, 0.35% for hydrocodone, and 0.33% for tramadol. Oxycodone was associated with a higher risk than hydrocodone (RR 1.48 [95% CI 1.30-1.69]; RD 0.17 [95% CI 0.11-0.22]) and tramadol (RR 1.55 [95% CI 1.33-1.79]; RD 0.18 [95% CI 0.12-0.24]). Hydrocodone and tramadol showed similar risks (RR 1.05 [95% CI 0.91-1.21]; RD 0.02 [95% CI -0.03 to 0.06]). CONCLUSIONS: Among adults with T2D who were using a GLP-1RA, initiation of oxycodone was associated with higher short-term risks of severe constipation and bowel obstruction compared with hydrocodone or tramadol. We did not observe differences in the risk of gastroparesis. Risks were similar between patients initiating hydrocodone and tramadol, although variation across secondary analyses warrants cautious interpretation.
Nature
Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is a heterogeneous and systemic disease that confers risk not only for cirrhosis and hepatocellular carcinoma (HCC) but also for extrahepatic complications including cardiovascular disease and chronic kidney disease. Over the past decade, numerous late-stage clinical trials have advanced the therapeutic landscape of MASH, culminating in a pivotal inflection point with accelerated approval of the thyroid hormone receptor-β (THRβ) agonist resmetirom and the glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide, establishing pharmacological options for patients with non-cirrhotic MASH and fibrosis. Concurrently, growing evidence indicates that MASH comprises distinct, partially overlapping disease subsets, ranging from liver-centric phenotypes with accelerated fibrogenesis and liver-related outcomes to cardiometabolic phenotypes characterized by insulin resistance and increased cardiovascular risk. This suggests that optimal treatment efficacy will require stratified and potentially combinatorial approaches. In addition to lifestyle interventions, a cornerstone of MASLD management, pharmacotherapies targeting metabolic dysfunction (including PPAR agonists, FGF21 analogues or incretin-based and glucagon-based therapies), fibrogenesis, inflammation and/or the gut-liver axis are emerging. In this Review, we summarize the therapeutic landscape for MASH and discuss how recent advances in disease phenotyping and biomarkers may enable a transition towards personalized therapy.
Nature
Pharmacological glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and is an effective therapy for type 2 diabetes and obesity. The use of GLP-1 medicines has revealed pleiotropic beneficial effects beyond glucose and weight control, but little is known about the underlying basis of the pleiotropic effects. Here, treatment of 20-month-old female C57BL/6 mice with the GLP-1R agonist semaglutide for 3 months improved physiological function, attenuated hallmarks of ageing and modulated nutrient sensors and conserved genetic regulators of ageing. Continued treatment extended mouse lifespan. These effects parallel key features of calorie restriction, a dietary intervention that slows ageing, extends lifespan and alleviates a wide spectrum of ageing-associated diseases. In a longitudinal study in direct comparison to matched calorie restriction, semaglutide treatment preserved baseline function and recapitulated many functional benefits of calorie restriction by attenuating age-associated decline, while also producing improvements above baseline and more favourable trajectories than calorie restriction in exploratory drive, spatial memory and glucose control. Together, these findings demonstrate that GLP-1R activation initiated late in life slows ageing and extends lifespan in female mice, supporting its function as a calorie restriction mimetic and providing a mechanistic framework that may help to explain its broad beneficial effects while revealing effects beyond those attributable to reduced calorie intake.
Nature
Metabolic dysfunction-associated steatotic liver disease (MASLD), including its progressive form metabolic dysfunction-associated steatohepatitis (MASH), represents the hepatic manifestation of metabolic syndrome and is increasingly recognized as a multi-organ disease. MASLD is now the most prevalent chronic liver disease worldwide and a rising indication for liver transplantation. MASLD incidence continues to increase, driven by sedentary lifestyles, the obesity epidemic and associated pathologies such as type 2 diabetes. MASH is a significant risk factor for fibrosis, cirrhosis and hepatocellular carcinoma (HCC)-a leading cause of cancer-related death. Over the past decade, substantial progress has been made in elucidating the molecular and cellular mechanisms driving MASLD initiation and progression. Key pathogenic processes include insulin resistance, genetic drivers, dysregulated hepatic lipid metabolism, lipotoxicity, adipose tissue dysfunction, immune-mediated inflammation, fibrogenesis and perturbations of the gut-liver axis. Increasingly, these mechanistic insights are informing clinical translation. Genetic risk variants and polygenic risk scores are beginning to enable improved risk stratification for disease progression and HCC. Furthermore, therapeutic strategies targeting defined metabolic pathways are emerging, including approaches that reduce hepatic lipogenesis or modulate mitochondrial metabolism. Here we highlight the state of the art of molecular and cellular mechanisms underlying MASH pathogenesis and its transition to HCC.
Diabetes care · ADA
Nature
Nature, Published online: 02 September 2026; doi:10.1038/d41586-026-02468-7 In one inbred strain of laboratory mice, late-life treatment with a GLP-1 drug extends lifespan. This effect might be more than just a consequence of calorie restriction.
Diabetes care · ADA
OBJECTIVE: Individuals with single islet autoantibody positivity exhibit a highly variable risk for type 1 diabetes progression. We evaluated whether metabolic measures identify those at higher progression risk. RESEARCH DESIGN AND METHODS: Among first- and second-degree relatives of persons with type 1 diabetes who screened and confirmed positive for a single autoantibody in the TrialNet Pathway to Prevention Natural History study, we used Cox proportional hazards models to assess associations between metabolic measures and time to progression, defined as the development of multiple autoantibody-positive or stage 3 type 1 diabetes. Random forest models were used to estimate the relative importance of each variable. Analyses were conducted in the overall cohort and stratified by age (0-8, ≥8-16, and ≥16 years). RESULTS: Individuals with single autoantibody positivity exhibited wide variation in metabolic function. Measures incorporating both oral glucose tolerance test-stimulated glucose and C-peptide to assess β-cell dysfunction showed strong and consistent associations with progression across age-groups and antibody profiles. Associations for traditional risk factors, isolated glucose or C-peptide measures, or indices of insulin resistance differed by age and autoantibody type. Data-driven cutoffs for combined metabolic measures identified small subsets at very high risk (>50% 2-year progression) and large low-risk groups with <10% 5-year progression. CONCLUSIONS: β-Cell dysfunction is present in many individuals with single autoantibody positivity and is associated with an increased risk of disease progression. Incorporating stimulated measures of β-cell function alongside age and autoantibody profiles may enable more personalized monitoring, help identify persons most likely to benefit from disease-modifying therapies, and delineate lower-risk individuals who require less intensive surveillance.
JAMA
This trial examined whether starting dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, 1 day prior to elective cardiac surgery reduces the risk of acute kidney injury (AKI) in the week following surgery compared with placebo.
JAMA network open
IMPORTANCE: Although modern radiotherapy (RT) techniques have reduced cardiac exposure, concerns regarding RT-induced heart disease persist. Identifying which patients are most vulnerable to cardiac toxic effects is crucial for personalized survivorship care. OBJECTIVE: To evaluate whether the association between tumor laterality and ischemic heart disease (IHD) risk varies by cumulative baseline cardiovascular risk burden. DESIGN, SETTING, AND PARTICIPANTS: This retrospective nationwide cohort study used data on 23 305 women in the Korean National Health Insurance Service database who underwent postoperative RT for breast cancer without prior IHD from January 1, 2002, to December 31, 2018. The median follow-up was 4.3 years (IQR, 2.5-6.5 years); data analysis was completed in March 2023. EXPOSURES: Treatment laterality (left-sided vs right-sided RT) and baseline cardiovascular risk burden (defined as a count of 6 factors: age ≥55 years, obesity, smoking, hypertension, diabetes, and dyslipidemia). MAIN OUTCOMES AND MEASURES: The cumulative incidence of IHD was estimated using competing-risk analysis. Subdistribution hazard ratios (sHRs) were calculated using Fine-Gray models. RESULTS: Of 23 305 patients (mean [SD] age, 51.7 [9.2] years), 11 723 (50.3%) received left-sided RT and 11 582 (49.7%) received right-sided RT. Left-sided RT was associated with a statistically significant increase in IHD risk (sHR, 1.11; 95% CI, 1.01-1.22; P = .04). No statistically significant difference in IHD risk between left- and right-sided RT was observed among patients with 0 to 2 cardiovascular risk factors, whereas left-sided RT was associated with significantly higher IHD risk among patients with 3 risk factors (adjusted sHR, 1.37; 95% CI, 1.10-1.71; Gray test P = .004). CONCLUSIONS AND RELEVANCE: In this cohort study of 23 305 women with breast cancer, excess cardiac risk associated with left-sided RT was concentrated among patients with 3 cardiovascular risk factors. These findings suggest that among patients with low baseline risk profiles, the difference in IHD risk between left- and right-sided treatment may be small, whereas those with high cardiovascular burden warrant prioritized access to advanced heart-sparing modalities and aggressive risk factor management.
The Journal of the American Academy of Orthopaedic Surgeons · AAOS
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) are used in diabetic patients for glycemic control. Yet, there has been a notable rise in their use for weight loss management in obese patients. This review critically appraises current evidence on perioperative implications of GLP-1 receptor agonists in TJA patients. The review discusses GLP-1 RA implications and use (physiology, pharmacology, pharmacodynamics, mechanisms of actions, and commonly used GLP-1 Ras), complications and adverse effects, considerations for the anesthesiologist, considerations for the TJA surgeon, and current clinical practice recommendations in 2025.
The New England journal of medicine
BACKGROUND: The effectiveness and safety of statins for the primary prevention of cardiovascular events and the extension of disability-free survival among older adults remain uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled trial at general medical practices across Australia. Community-dwelling adults at least 70 years of age with no history of cardiovascular disease, diabetes, or dementia were randomly assigned in a 1:1 ratio to receive atorvastatin at a dose of 40 mg once daily or identical placebo. The two primary end points were a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke, or coronary revascularization (to assess effects on major cardiovascular events) and a composite of death from any cause, dementia, or persistent physical disability (to assess effects on disability-free survival). Analyses were performed according to a hierarchical testing plan. RESULTS: A total of 9971 participants were enrolled: 4984 were assigned to receive atorvastatin and 4987 to receive placebo. The mean (±SD) age of the participants was 74.7±4.5 years, and 51.9% were women. After a median of 5.9 years, a primary cardiovascular event had occurred in 297 participants (10.9 events per 1000 person-years) in the atorvastatin group and in 412 participants (15.5 events per 1000 person-years) in the placebo group (hazard ratio, 0.70; 95% confidence interval [CI], 0.61 to 0.82; P<0.001). Death from any cause, dementia, or persistent physical disability occurred in 637 participants (21.6 events per 1000 person-years) in the atorvastatin group and in 676 participants (23.0 events per 1000 person-years) in the placebo group (hazard ratio, 0.94; 95% CI, 0.84 to 1.05; P = 0.25). Serious adverse events occurred in 131 participants (2.7%) in the atorvastatin group and in 129 (2.7%) in the placebo group, with musculoskeletal, hepatobiliary, and diabetes-related adverse events occurring more commonly in the atorvastatin group. CONCLUSIONS: Treatment with atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival among community-dwelling older adults without clinical cardiovascular disease. (Funded by the National Health and Medical Research Council and others; STAREE ClinicalTrials.gov number, NCT02099123.).
Journal of the American College of Cardiology · ACC
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab reduced the risk of a first major adverse cardiovascular event (MACE) in patients at high cardiovascular risk with no prior myocardial infarction (MI) or stroke in the VESALIUS-CV (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke) trial. Recurrent MACE is common and important to patients, clinicians, and health care systems. OBJECTIVES: The purpose of this study was to evaluate the effect of evolocumab on total (first and subsequent) MACE. METHODS: The VESALIUS-CV trial randomized patients with qualifying atherosclerosis or high-risk diabetes, no prior MI or stroke, and a low-density lipoprotein cholesterol ≥90 mg/dL on optimized lipid-lowering therapy to evolocumab or placebo. The dual primary endpoints were a composite of coronary heart disease death, MI, ischemic stroke, or ischemia-driven arterial revascularization (4-point [4-P] MACE) and 3-point (3-P) MACE (not including ischemia-driven arterial revascularization). In this prespecified analysis, all dual primary endpoint events (first and subsequent) were analyzed using negative binomial regression models. RESULTS: Among 12,257 patients followed for a median of 4.6 years, there were 1,654 first 4-P MACE and 1,107 subsequent events (67% more) for 2,761 total events. There were 779 first 3-P MACE and 146 subsequent events (19% more) for 925 total events. Evolocumab reduced the rate of first 4-P MACE by 19% (HR: 0.81; 95% CI: 0.73-0.89; P < 0.0001), was associated with a reduction of subsequent events by 25% (incidence rate ratio [IRR]: 0.75; 95% CI: 0.61-0.91), and reduced total events by 20% (IRR: 0.80; 95% CI: 0.71-0.90; P = 0.0002). Likewise for 3-P MACE, evolocumab reduced the rate of first events by 25% (HR: 0.75; 95% CI: 0.65-0.86; P < 0.0001), was associated with a reduction of subsequent events by 37% (IRR: 0.63; 95% CI: 0.42-0.94) and reduced total events by 27% (IRR: 0.73; 95% CI: 0.63-0.86; P = 0.0001). Based on annualized incidence rate differences over the full follow-up period, evolocumab was projected to prevent 31 first and 24 subsequent 4-P MACE, for 55 total events per 1,000 patients over 5 years (95% CI: for the total-event difference: 36-74). The corresponding estimates for 3-P MACE were 20 first and 5 subsequent events, for 25 total events per 1,000 patients over 5 years (95% CI: for the total event difference: 15-37). Results were consistent across key subgroups, including by statin intensity and presence of qualifying atherosclerosis. CONCLUSIONS: A substantial proportion of patients experiencing a cardiovascular event had more than 1 event. The addition of evolocumab reduced the total number of MACE, providing support for the role of intensive low-density lipoprotein cholesterol lowering to prevent first and subsequent MACE in patients at high cardiovascular risk and no prior MI or stroke. (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]; NCT03872401).
Diabetes care · ADA
OBJECTIVE: To examine the effect of the Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) diet (a DASH-style diet tailored for diabetes) on biomarkers of glycemia. RESEARCH DESIGN AND METHODS: In this controlled feeding trial, adults with type 2 diabetes were fed four diets in a random order: DASH4D diet and comparison diet (representative of a typical American diet), each with higher and lower sodium. Each feeding period lasted 5 weeks. Using a modified intention-to-treat approach, we estimated the effect of the DASH4D (versus comparison) diet on fructosamine, fasting glucose, and HbA1c with linear mixed-effects models. RESULTS: Among 101 participants (mean age 67 years, 65% female, 87% Black adults), compared with the comparison diet, the DASH4D diet significantly reduced end-of-period fructosamine (adjusted difference: -5.6 μmol/L, P = 0.002), fasting glucose (adjusted difference: -4.5 mg/dL; P = 0.02), and HbA1c (adjusted difference: -0.09 percentage points; P = 0.04). CONCLUSIONS: Our results support recommending the DASH4D diet for glycemic management in type 2 diabetes.
Diabetes care · ADA
Diabetes care · ADA
OBJECTIVE: Independent of clinical risk factors, performing well-day capillary ketone monitoring over a month predicts near-term diabetic ketoacidosis (DKA) risk. We aimed to determine the minimum frequency of tests needed to maintain similar accuracy. RESEARCH DESIGN AND METHODS: Using regression and machine-learning gradient-boosted tree (GBT) models on the Empagliflozin as Adjunctive to Insulin Therapy 2 (EASE 2) and EASE 3 trial repository (n = 1,410), we simulated the testing frequencies of capillary ketones over a 1-month interval for predicting DKA or severe ketosis in the next month. RESULTS: Compared with the baseline twice-weekly ketone testing frequency, once-weekly well-day ketone testing was the lowest frequency that maintained prediction accuracy in maximum ketone models (area under the receiver operating characteristic curve 0.692 vs. 0.678; P = 0.19) and GBT models (0.719 vs. 0.711; P = 0.38). CONCLUSIONS: Weekly well-day capillary ketone testing, using existing strips before they expire, may provide a practical approach to stratify baseline DKA risk while reducing testing burden.
Diabetes care · ADA
OBJECTIVE: We examined how cardiovascular health (CVH), measured by Life's Essential 8 (LE8), and genetic risk are jointly associated with risks of mild cognitive impairment (MCI), dementia, and related cognitive outcomes in people with diabetes. RESEARCH DESIGN AND METHODS: We analyzed 41,374 participants without dementia from the UK Biobank (UKB) and 9,766 from All of Us (AoU). LE8, comprising diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure, was scored from 0 to 100 and categorized as low, moderate, or high. Genetic risk was assessed using APOE ε4 alleles and polygenic risk scores (PRS) for Alzheimer disease. We used Cox regression to examine associations of LE8 with MCI and dementia and linear regression to assess MRI-based brain functional measures and cognitive test outcomes, adjusting for covariates. Interactions between LE8 and genetic risk were tested on multiplicative and additive scales. RESULTS: Over 15 years of follow-up (UKB), moderate or high CVH versus low CVH was associated with a lower risk of MCI (hazard ratio 0.82 [95% CI 0.71, 0.95], P < 0.05) but not with risk of all-cause dementia (0.97 [0.84, 1.11], P = 0.63). In participants at high genetic risk (high PRS), moderate or high CVH was associated with a lower risk of MCI (0.78 [0.62, 0.98], P for additive interaction < 0.05). AoU results were consistent. CONCLUSIONS: Better CVH was significantly associated with a lower risk of MCI in people with diabetes, accounting for genetic risk. The association between CVH and MCI and dementia was stronger among individuals with low or moderate genetic risk and appeared attenuated among those with high genetic risk.
Diabetes care · ADA
OBJECTIVE: Energy restriction and weight loss are evidence-based, safe, and well-tolerated methods for lowering glycemia in type 2 diabetes. We assessed if imposed energy restriction or natural weight loss in the third trimester in women with gestational diabetes was associated with maternal and offspring weight postnatally. RESEARCH DESIGN AND METHODS: Women with gestational diabetes and BMI ≥25 kg/m2 were randomized to a standard- (2,000 kcal/day) or reduced-energy (1,200 kcal/day) diet from ∼29 to -36 weeks' gestation, with follow-up to 12 months postnatally. We performed both trial and cohort analyses, using adjusted linear and logistic regression and a Super-Imposition by Translation and Rotation model. RESULTS: Allocation to energy restriction did not alter antenatal or postnatal growth, with infants in both randomized groups having normal weight for age throughout the first year of life. In cohort analysis, women who lost weight in pregnancy (average loss of 3 kg) had lower adjusted weight at 3 but not 12 months. Infants exposed to pregnancy weight loss had lower risk of large-for-gestational age at birth and lower fat mass at 3 months, and no higher prevalence of low infant weight (<5% had weight for age < -2 SD). Infants exposed to weight loss in pregnancy showed no evidence of growth faltering or excessive catch-up or catch-down growth. CONCLUSIONS: Among women with gestational diabetes and high BMI, energy restriction or weight loss in pregnancy were associated with no adverse effects on offspring weight or growth in the first year. Future work will assess associations with child obesity at 3 years.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · AAO-HNS
OBJECTIVE: Microvascular free flap reconstruction is the gold standard for head and neck defects, but flap compromise remains a primary cause of reconstructive failure. This study aims to evaluate the pooled incidence of flap compromise and total flap failure, and to identify risk factors to optimize perioperative management. DATA SOURCES: A systematic search was conducted across PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science for studies published up to September 1, 2025. REVIEW METHODS: This meta-analysis followed the PRISMA guidelines. Two independent reviewers screened the literature, extracted data, and assessed study quality using the Newcastle-Ottawa Scale (NOS). Random-effects models were used to calculate pooled incidences and odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Forty-seven studies involving 30,002 free flaps were included. The pooled incidence of flap compromise was 8.2% (95% CI: 6.6%-9.9%), with a complete failure rate of 3.9% (95% CI: 3.2%-4.7%). Flap compromise was significantly associated with prior radiotherapy (OR = 3.98). Other significant non-modifiable factors included diabetes (OR = 2.20), advanced age (OR = 1.35), and high comorbidity scores (OR = 1.68). Importantly, several modifiable factors were identified as critical drivers, including fluid overload (OR = 2.57), prolonged operative time (OR = 2.14), low serum albumin (OR = 2.06), low BMI (OR = 1.75), and low hemoglobin (OR = 1.34). CONCLUSION: Free flap compromise remains a clinically significant complication. These findings support integrating modifiable physiological markers into preoperative risk stratification and implementing targeted, multidisciplinary optimization strategies to improve flap outcomes.
Journal of the American College of Cardiology · ACC
Diabetes care · ADA
Diabetes care · ADA
OBJECTIVE: The safety and efficacy of HTD1801 versus placebo were evaluated in participants with type 2 diabetes inadequately controlled with diet and exercise. RESEARCH DESIGN AND METHODS: Key entry criteria of this phase 3, randomized, placebo-controlled trial included type 2 diabetes (per World Health Organization guidelines), HbA1c 7.0-10.5% (53-91 mmol/mol), fasting plasma glucose ≤13.9 mmol/L, and ≥8 weeks of diet and exercise. Participants were randomized and treated 2:1 to HTD1801 1,000 mg twice daily (BID) (n = 271) or placebo (n = 136). The primary end point was the change from baseline in HbA1c at week 24. After completion of a 24-week, double-blind trial, participants could enter a 28-week open-label extension during which everyone received HTD1801 1,000 mg BID. Safety was assessed for 56 weeks. RESULTS: Baseline HbA1c was 8.5% (69 mmol/mol) in both groups. The primary end point was achieved: HTD1801-treated participants achieved a change in HbA1c of -1.3% versus -0.6% with placebo (least squares mean difference -0.7%; 95% CI -0.8, -0.5; P < 0.0001). After 24 weeks of HTD1801 treatment, significant improvements were observed in key cardiometabolic and inflammatory markers. HbA1c reductions were durable through 52 weeks. The most common adverse events were mild to moderate diarrhea (HTD1801: n = 26 participants [9.6%]; placebo: n = 1 participant [0.7%]); most of which occurred at treatment initiation. Longer-term safety (56 weeks) was consistent with safety findings of the double-blind trial. CONCLUSIONS: HTD1801 treatment produced sustained improvements in glycemic, cardiometabolic, and inflammatory parameters, supporting further evaluation as a well-tolerated oral therapy for patients with type 2 diabetes.
Diabetes care · ADA
Diabetes · ADA
Accurate diagnosis of diabetes has important therapeutic consequences, yet 10-15% of individuals with type 1 diabetes are autoantibody negative, leaving the etiology of diabetes unconfirmed. We estimated what proportion of autoantibody negative, clinically diagnosed type 1 diabetes is misdiagnosed nonautoimmune diabetes. Upwards of 7.6% of autoantibody negative individuals are nonautoimmune. Our findings support the use of autoantibody screening and genetic testing of autoantibody negative patients as standard of care for type 1 diabetes.
Diabetes care · ADA
OBJECTIVE: Selective glucagon-like protein 1 receptor (GLP-1R) agonists reduce body weight and improve cardiometabolic risk factors. However, whether dual GLP-1R and glucagon receptor (GCGR) agonism modifies these cardiometabolic effects remains unclear. Here, we assessed the effects of dual GLP-1R/GCGR agonists on cardiometabolic risk factors across randomized controlled trials. RESEARCH DESIGN AND METHODS: In this random-effects meta-analysis, Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, and Cochran Central Register of Controlled Trials (CENTRAL) were searched from database inception to 21 June 2026 for randomized controlled trials evaluating clinical efficacy of dual GLP-1R/GCGR agonists in adults with cardiometabolic disease with a treatment duration ≥12 weeks. The primary outcome was placebo-corrected change in body weight from baseline to end of treatment. Secondary outcomes were changes in waist circumference, atherogenic lipids (total cholesterol, LDL cholesterol, and triglycerides), glycated hemoglobin, and hemodynamic outcomes. Prespecified subgroup analyses evaluated effect modification by dose, treatment indication, and the use of an active comparator (selective GLP-1R agonists). RESULTS: A total of 6,593 records were identified, and 16 trials comprising 6,611 participants (47.3% male) were included. Dual GLP-1R/GCGR agonists significantly reduced body weight compared with placebo (-7.44% [95% CI -9.44, -5.43]; -7.27 kg [95% CI -9.28, -5.27]). Weight loss was accompanied by improvements across all cardiometabolic risk factors. Compared with selective GLP-1R agonists, dual GLP-1R/GCGR agonists were associated with a greater reduction in triglycerides (-0.28 mmol/L [95% CI -0.50, -0.06]). CONCLUSIONS: Dual GLP-1R/GCGR agonists consistently improved cardiometabolic risk factors across randomized clinical trials and may provide metabolic benefits beyond selective GLP-1R agonists. These findings support further evaluation in large-scale outcome studies.
JAMA
Diabetes · ADA
The exercise-induced hormone irisin plays an important role in the regulation of glucose homeostasis; however, its underlying mechanisms under insulin-deficient conditions remain unclear. We investigated whether irisin can directly regulate hepatic glucose metabolism and manage diabetic phenotypes in insulin-deficient Akita mice. Irisin improved diabetic phenotypes and was associated with enhanced glucose uptake (peroxisome proliferator-activated receptor-γ/GLUT2/GCK axis), increased glycogen storage (GSK-3β-dependent and GSK-3β-independent pathways), and reduced gluconeogenic activity, accompanied by increased AMPK phosphorylation independently of increases in insulin levels. These findings identify irisin as an insulin-independent regulator in hepatic glucose metabolism and suggest a potential therapeutic strategy for insulin-deficient diabetes.
Diabetes care · ADA
Asia confronts a disproportionately high diabetes burden, characterized by aggressive pathophysiology and early-onset complications. For addressing this crisis, established therapeutic agents are actively leveraged across Asia via multifaceted approaches, e.g., developing fixed-dose combinations to improve adherence or optimizing drug structures to enhance therapeutic profiles. Concurrently, Asian innovators are advancing emerging target-based agent classes into clinical use, including glucagon-like peptide 1 multiagonists, glucokinase activators, pan-peroxisome proliferator-activated receptor modulators, AMP-activated protein kinase/NOD-like receptor family pyrin domain-containing 3 dual targeted compound, glimins-class oral small molecule, and G-protein-coupled receptor 119 receptor agonist, etc. Technologies such as antisense oligonucleotide (ASO) inhibitors targeting glucagon receptor, stem cell therapy, and microbiome-based glycemic management are also being clinically validated in Asia. Meanwhile, devices such as continuous glucose monitoring, automated insulin delivery systems, and noninvasive glucose monitors are advancing toward broader clinical adoption. This review critically synthesizes Asia's contemporary strategies against diabetes, spanning from the optimization of established target-based agents to the breakthroughs of novel therapeutics and the advancement of maturing technologies and devices. This evolution reflects Asia's accelerating transition from a major clinical trial hub and product consumer to a global driver and leader in innovative glucose-lowering drug development. Propelled by pioneering drug innovators, surging research and development investment, and robust multistakeholder collaboration across industry, academia, and health care, the region is fostering a dynamic innovation ecosystem. Through synergistically advancing the research and application of glucose-lowering therapeutics alongside context-adapted implementation, Asia's practical experience delivers a referable approach for diabetes management across the globe and promotes sustained innovation within diabetology.
Diabetes care · ADA
OBJECTIVE: The Baricitinib in New-Onset Type 1 Diabetes (BANDIT) trial showed that baricitinib treatment for 48 weeks preserved β-cell function and lowered insulin requirements and glucose in recent-onset type 1 diabetes. We aimed to determine the durability of these effects following treatment cessation. RESEARCH DESIGN AND METHODS: The following posttreatment outcomes of the randomized, double-blind, placebo-controlled BANDIT trial were analyzed: C-peptide and glucagon responses to a mixed meal, HbA1c, continuous glucose monitoring (CGM) measures, CD8+ T-cell phenotype and function, and adverse events. RESULTS: Of 91 randomized participants, 88 (58 baricitinib and 30 placebo) completed the week 96 follow-up. Mean ± SEM C-peptide was significantly greater in baricitinib-treated participants at week 72 (0.54 ± 0.05 vs. 0.38 ± 0.06 pmol/mL; P = 0.015) but not at week 96 (0.43 ± 0.05 vs. 0.35 ± 0.06 nmol/L; P = 0.336). No significant between-group differences in insulin dose, HbA1c, or CGM measures were observed during follow-up. Post hoc comparisons showed that when the study drug was ceased at week 48, baricitinib-treated adults (n = 28) experienced full preservation of β-cell function whereas C-peptide decreased relative to baseline by 0.09 pmol/mL in baricitinib-treated children (n = 32; P = 0.022). Baricitinib did not resolve paradoxical glucagon increase after a mixed meal. Decreased frequency and cytokine signaling of effector memory CD8+ T cells observed at week 48 resolved by week 96. CONCLUSIONS: The benefits of oral baricitinib in type 1 diabetes wane over 48 weeks following treatment cessation. Durable benefit is likely to require continuous treatment.
Diabetes care · ADA
Diabetes care · ADA
Adrian Vella had never seen snow before. Growing up on the island of Malta, he spent his childhood swimming and snorkeling in the Mediterranean with his family. But after accepting a position at the Mayo Clinic, Vella took the long flight to Rochester, Minnesota. A new country, a new career, a new climate. “This was 1995, one of Minnesota’s coldest winters on record,” he says. “So I was dropped in
Diabetes care · ADA
Graphical Abstract Continuous glucose monitoring is presented from established glycemic benefits to intermediate outcomes, uncertain long-term outcomes, and research challenges. Known effects include lower glycated hemoglobin, more time in range, less hypoglycemia, and lower glycemic variability. Intermediate outcomes include reduced severe hypoglycemia, fewer hospitalisations, and improved qualit
Diabetes care · ADA
We read with great interest the study by Di Marco et al. ( 1 ) published in Diabetes Care . By integrating observational analyses with genetic evidence, the authors investigated the relationships among diabetes, metabolic factors, and alterations in lung function. We commend the authors for their important work; however, we would like to raise several methodological considerations and suggestions.
Diabetes care · ADA
We read with great interest the recent editorial by Kahn et al. ( 1 ) that highlighted threats to the biomedical research infrastructure of the U.S. While the concerns raised are compelling, we believe that these challenges extend beyond the U.S. and reflect broader vulnerabilities affecting biomedical research systems globally.
Diabetes care · ADA
Graduate Program, People’s hospital of Yuxi Cityyys2024-20
Diabetes care · ADA
Sichuan Hospital Management and Development Research CenterSCYG2025-1
Diabetes care · ADA
We read with interest the report by Ostrominski et al. ( 1 ), which used two target-trial emulations to compare tirzepatide with dulaglutide or semaglutide among patients with type 2 diabetes and established atherosclerotic cardiovascular disease. The study is timely and carefully constructed. Our concern is not whether a statistical contrast was observed but what that contrast represents: superio
Diabetes care · ADA
We read with great interest about the study by Pop-Busui et al. ( 1 ), which demonstrated the prognostic value of natriuretic peptide (NP) levels in a large, real-world cohort of 116,466 individuals with diabetes. While the association between NP levels and future risk is compelling, the definition used for incident heart failure (HF) raises important questions regarding potential bias.
Diabetes care · ADA
Gestational diabetes mellitus (GDM), traditionally defined as hyperglycemia first detected during pregnancy less than overt diabetes, is associated with greater risk of pregnancy complications and cardiometabolic disease and is one of the most common medical complications of pregnancy, now affecting over 15% of women globally ( 1 , 2 ).
Diabetes · ADA
“They say first impressions are important,” John Ussher says. He remembers giving a research presentation during his undergraduate years at the University of Alberta, his first time speaking publicly in front of a room full of professors. “There was no laser pointer,” he says. “I had a wooden stick, I was nervous, and I was waving it so wildly that I nearly whacked anyone sitting in the front row.
Diabetes care · ADA
Gestational diabetes mellitus (GDM) has long been viewed as a metabolic condition first recognized during pregnancy. However, research now demonstrates that underlying metabolic abnormalities are detectable during the preconception period in individuals who subsequently develop GDM and that GDM carries long-term implications for both mothers and offspring. In this article, I provide an overview of the work that my colleagues and I have conducted over the past 25 years, aimed at understanding when GDM risk emerges, how risk can be modified, and how intrauterine exposure to hyperglycemia and its treatment influences health across the life course. This work spans population-based epidemiology, preconception biomarker studies, efficacy prevention trials, and pragmatic interventions embedded within an integrated health care system. Together, these findings affirm Norbert Freinkel's concept of fuel-mediated teratogenesis and underscore the need for precision prevention and treatment strategies that address biological, behavioral, and social determinants of health risk factors.
Diabetes Care · ADA
Diabetes · ADA
Diabetes · ADA
German Center for Diabetes Research
Diabetes care · ADA
We thank Zhang et al. ( 1 ) for their comments on our work on pulmonary function and diabetes, particularly regarding the Mendelian randomization (MR) analysis assessing the causal effect of HOMA of insulin resistance (HOMA-IR) on lung function ( 2 ).
Diabetes care · ADA
National Center for Advancing Translational Sciences10.13039/100006108K12TR004416Novo Nordisk10.13039/501100004191
Diabetes care · ADA
Roche Diagnostics Corporation
The Journal of the American Academy of Orthopaedic Surgeons · AAOS
BACKGROUND: Diabetes mellitus (DM) is a well-established risk factor for complications after surgical fixation of ankle fractures. Elevated hemoglobin A1c (HbA1c) has been associated with worse outcomes; however, it remains unclear whether HbA1c alone predicts perioperative risk independent of a formal DM diagnosis and treatment status. This study evaluated whether elevated preoperative HbA1c (≥8.0%) in patients without a documented diagnosis or pharmacologic treatment of DM is associated with increased early postoperative complications compared with patients with established DM. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2021 to 2024) was queried for patients undergoing open reduction and internal fixation of ankle fractures. Patients were stratified into four cohorts based on diabetes diagnosis/treatment status and glycemic control: (1) undiagnosed/untreated, HbA1c < 8.0%; (2) undiagnosed/untreated, HbA1c ≥ 8.0%; (3) diagnosed/treated, HbA1c < 8.0%; and (4) diagnosed/treated, HbA1c ≥ 8.0%. Propensity score matching (1:1) on age and sex yielded 388 matched patients (n = 97 per group). Primary outcomes were 30-day mortality, readmission, and revision surgery. Secondary outcomes included surgical site infection, organ-space infection, and medical complications. Multivariable logistic regression adjusted for residual differences in body mass index and comorbidities. RESULTS: Thirty-day mortality was rare (0.8%) and did not differ between groups (P = 0.381). Significant differences were observed in revision surgery (P = 0.006), superficial surgical site infection (P = 0.003), and organ space infection (P = 0.019). Patients with diagnosed/treated uncontrolled DM had higher odds of these complications compared with those with elevated HbA1c but no documented DM diagnosis or treatment (undiagnosed/untreated uncontrolled) (all P < 0.05). CONCLUSION: Patients with poorly controlled established diabetes had higher rates of early postoperative complications after ankle fracture open reduction and internal fixation compared with those with elevated HbA1c but no earlier diabetes diagnosis or treatment. Assessment of the presence and treatment status of diabetes may provide more meaningful perioperative risk stratification than HbA1c level alone. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
Diabetes care · ADA
Diabetes care · ADA
Division of Diabetes, Endocrinology, and Metabolic Diseases10.13039/100017618R01DK125780
Diabetes care · ADA
OBJECTIVE: Waist circumference-based measures can improve diabetes risk assessment beyond BMI. Yet, evidence to guide their integration into screening guidelines in low- and middle-income countries (LMICs) is limited, particularly to assess risk among individuals at intermediate BMI ranges. We evaluated the associations of waist circumference (WC), relative fat mass (RFM), and BMI with diabetes across 82 LMICs. RESEARCH DESIGN AND METHODS: Individual-level data were analyzed from nationally representative surveys across 82 LMICs, comprising 598,883 adults aged ≥25 years with a BMI of 18.5-29.9 kg/m2. Associations of anthropometric measures with diabetes were estimated as risk ratios using Poisson regression and area under the curve (AUC), stratified by sex and geographic region. RESULTS: Pooled diabetes prevalence was 9.1% (95% CI 8.51-9.68). Overall, risk of diabetes was greatest for WC and RFM at the highest quintile, compared with BMI. The AUC for WC and RFM as a classifier of diabetes status was higher than the AUC for BMI in men (AUC: WC 0.69, RFM 0.69, BMI 0.64) and women (AUC: WC 0.69, RFM 0.69, BMI 0.63). Generally, the AUC for RFM was higher than the AUC for BMI and either higher than or equal to WC across regions and sex. CONCLUSIONS: WC and RFM outperformed BMI as classifiers of diabetes status among adults with a BMI of 18.5-29.9 kg/m2 across 82 LMICs. Inclusion of WC-based measures in diabetes screening guidelines could improve timely diabetes detection and resource allocation in LMICs among individuals at intermediate BMI ranges.
Diabetes · ADA
Despite extensive research on the role of the hepatocyte growth factor (HGF)/c-Met pathway in β-cells and glucose homeostasis, the endogenous source of HGF in islets remains unclear. This study characterizes the pancreatic source of HGF and its physiological requirement in vivo. Pericytes were identified as the primary endogenous source of HGF in human and mouse islets. Pericytic HGF loss causes glucose intolerance by impairing insulin production through the regulation of key β-cell genes. Establishing β-cell mass during embryogenesis and pregnancy depends on mesenchymal/pericytic HGF. This study establishes the islet vasculature as a source of trophic factors required for glycemic control.
Diabetes · ADA
We believed that baseline serum metabolomic signatures can predict response to immunotherapies to identify which individuals will benefit most from treatment. We aimed to identify whether baseline serum metabolomic profiles can distinguish responders from nonresponders to teplizumab. Fifteen metabolites were identified as significantly different. Our findings suggest that baseline serum metabolomic signatures could be used to predict which newly diagnosed type 1 diabetes patients will respond to teplizumab, enabling more personalized treatment decisions.
Diabetes care · ADA
OBJECTIVE: To evaluate the clinical utility of incorporating a type 1 diabetes genetic risk score (T1DGRS) into monogenic diabetes gene panel testing for individuals referred for suspected maturity-onset diabetes of the young (MODY) from routine clinical practice. RESEARCH DESIGN AND METHODS: We studied 1,129 individuals treated with insulin referred for MODY genetic testing. All underwent gene panel testing that included 10 variants to calculate T1DGRS. We compared T1DGRS distributions with reference populations to estimate the T1D prevalence within referred individuals. We defined age-specific T1DGRS thresholds to identify probable T1D (positive predictive value ≥80%) and applied them in individuals genetically unsolved MODY to assess its utility as a pregenetic testing triage tool. RESULTS: T1DGRS in MODY referral individuals was intermediate between reference populations with and without T1D, consistent with an estimated 20% (95% CI 14.9-25.2%) T1D in this real-world setting. After genetic testing, no excess T1DGRS was observed in individuals with genetically solved MODY, whereas those with unsolved MODY showed enrichment consistent with 26.0% T1D, with highest values in children (76.2%) and lowest in adults (16.8%). Age-specific T1DGRS thresholds identified 16.1% (95% CI 13.8-18.5%) of genetically unsolved MODY as probable T1D. As a pretesting tool, T1DGRS showed limited discrimination overall (area under the curve [AUC] 0.60) but performed well in children aged <10 years (AUC 0.83), where >50% of tests could be avoided without missing MODY. CONCLUSIONS: Incorporating a T1DGRS into routine MODY gene panel testing is feasible and clinically valuable. This approach broadens genomic diagnostics beyond monogenic disease by identifying T1D in individuals with genetically unsolved MODY. Pregenetic testing utility is age dependent and may reduce unnecessary testing in pediatric patients.
Diabetes · ADA
Subcellular accumulation of lipids is linked to insulin resistance, but changes in localization from weight loss or exercise training have not been thoroughly explored. We evaluated the independent effects of two insulin-sensitizing interventions, weight loss and exercise training, on lipid subcellular distribution in fractionated skeletal muscle, muscle mitochondrial function, and gene expression. Exercise training increased cytosolic storage of diacylglycerols and sphingolipids, and weight loss increased cytosolic sphingosine and decreased mitochondrial/endoplasmic reticulum triacylglycerol and diacylglycerol accumulation. Exercise training prevented the negative effects of mitochondrial lipids on mitochondrial function. Changes in specific subcellular lipid storage help explain muscle insulin sensitization following lifestyle interventions.
Diabetes care · ADA
OBJECTIVE: The epidemiology of diabetes and its complications is changing due to increasingly younger ages of diagnosis and increased life expectancy. How this changing landscape affects health care use, and for which conditions, is unclear. We examined age-specific excess burdens of cause-specific inpatient and emergency department (ED) visits associated with diabetes. RESEARCH DESIGN AND METHODS: We used 2019 Behavioral Risk Factor Surveillance System, National Inpatient Sample, and Nationwide Emergency Department Sample data to derive national U.S. estimates of inpatient admissions and ED visits in adults with and without diabetes. Complications were categorized as traditional, conditions emerging as diabetes associated, or other conditions co-occurring with diabetes. We calculated age-standardized absolute risk differences (ARDs) in people with versus without diabetes to identify leading causes of diabetes-related hospital use by age and setting. RESULTS: Traditional complications were dominated by sepsis, cardiorenal disease, acute kidney failure, myocardial infarction, and stroke, with ARDs ranging from 296 to 2,623 per 100,000 people with diabetes. Emerging conditions included pneumonia, device- and procedure-related complications (ARD range 125-473), and schizoaffective or other mental health disorders in younger adults only (ARD range 80-312). Other conditions included respiratory and fluid/electrolyte disorders across all ages (ARD range 100-363), while digestive and urinary disorders were more prominent in older adults (ARD range 229-482). ED visits showed a similar pattern, with lower ARD than inpatient admissions (ARD range 101-707). CONCLUSIONS: Diabetes drives substantial, age-specific excess inpatient and ED use, increasingly due to nontraditional rather than classic vascular and renal complications.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · AAO-HNS
OBJECTIVE: To evaluate glucagon-like peptide 1 receptor agonists for obstructive sleep apnea compared with controls. DATA SOURCES: CINAHL, Cochrane Library, PubMed, and Scopus. REVIEW METHODS: A PRISMA-compliant search was conducted from database inception through October 2025. Randomized controlled trials evaluating glucagon-like peptide 1 receptor agonist use (liraglutide and tirzepatide) for obstructive sleep apnea were included. The primary outcome was the change in apnea-hypopnea index. Data on apnea-hypopnea index, body weight, waist circumference, blood pressure, inflammatory markers, and adverse events were extracted and stratified by continuous positive airway pressure use. Outcomes were summarized as mean differences (Δ) with 95% confidence intervals (CI). Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. RESULTS: Of 3,836 articles screened, five studies met the inclusion criteria, comprising 948 patients (479 GLP-1; 469 control). Glucagon-like peptide 1 receptor agonists reduced apnea-hypopnea index by 12.4 events/hour more than controls (95% CI: -17.2 to -7.7; P < .00001), independent of continuous positive airway pressure use. Glucagon-like peptide 1 receptor agonists produced greater weight loss (Δ: -12.5%; 95% CI: -22.0% to -3.0%; P = .01) and reduced waist circumference (Δ: -3.3 cm; 95% CI: -4.4 to -3.2; P < .00001). Systolic and diastolic blood pressure decreased by 4.5 mmHg (95% CI: -6.4 to -2.7) and 1.30 mmHg (95% CI: -2.59 to -0.01), respectively. Gastrointestinal adverse events were more common with glucagon-like peptide 1 receptor agonists. CONCLUSION: Glucagon-like peptide 1 receptor agonists produced clinically meaningful improvements in obstructive sleep apnea severity, independent of continuous positive airway pressure use.
The Cochrane database of systematic reviews · Cochrane
RATIONALE: Obesity and its associated comorbidities, particularly type 2 diabetes (T2D), have reached epidemic dimensions globally. Both conditions are related to an increased risk of serious health outcomes and impose a substantial burden on those affected. Metabolic and bariatric surgery (MBS) may offer a therapeutic option for achieving sustained weight loss, improving comorbidities and thereby enhancing long-term quality of life. OBJECTIVES: To investigate the medium- and long-term benefits and harms of different MBS procedures compared with each other and to non-surgical treatment on outcomes relevant to adults with obesity and T2D, and to obtain a clinically meaningful ranking of these interventions by considering both randomised controlled trials (RCTs) and cohort studies. SEARCH METHODS: We searched MEDLINE, Cochrane CENTRAL, CINAHL, LILACS, BASE as well as the WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 25 June 2024. We did not apply any language restrictions. ELIGIBILITY CRITERIA: We included RCTs and both prospective and retrospective cohort studies with a minimum follow-up of three years in adults (≥ 18 years) with obesity (body mass index ≥ 30 kg/m² or ethnic-specific cut-off values) and T2D. Eligible interventions include MBS procedures (i.e. laparoscopic adjustable gastric banding [LAGB], sleeve gastrectomy [SG], Roux-en-Y gastric bypass [RYGB], one-anastomosis gastric bypass [OAGB], gastric plication [GCP], biliopancreatic diversion with duodenal switch, and their variations) or non-surgical treatment (i.e. lifestyle intervention, medical treatment [LI/MT]). OUTCOMES: Critical outcomes were medium- (≥ 3 to < 5 years) and long-term (≥ 5 years) weight loss (%), waist circumference (cm), T2D remission (complete, partial), and serious adverse events (SAE). Important outcomes included all-cause mortality, T2D complications, glycaemic control (glycated haemoglobin (HbA1c) in %) and health-related quality of life (HRQoL). RISK OF BIAS: We used the Risk of Bias 2 (RoB 2) tool for RCTs and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for cohort studies. SYNTHESIS METHODS: We performed random-effects network meta-analyses based on the frequentist approach and ranked treatments by P scores. We rated the certainty of evidence according to the GRADE approach for long-term outcomes (≥ 5 years). INCLUDED STUDIES: We included 18 studies (with 70 reports) with 15,282 participants in this review. Of these, 13 studies were RCTs (n = 911) and five were cohort studies (n = 14,371). Two RCTs compared MBS with LI/MT, ten compared two or three different MBS procedures and one with a 3-arm design investigated two different MBS procedures as well as LI/MT. All cohort studies compared different MBS procedures. The networks were based on the following MBS procedures: RYGB, SG, OAGB, LAGB, GCP, and LI/MT. SYNTHESIS OF RESULTS: NMA results (8 RCTs; n = 491) suggest greater long-term weight loss after RYGB compared to LI/MT (MD -16.95%; 95% CI -24.19 to -9.71). OAGB (MD -12.10%; 95% CI -22.85 to -1.34) and SG (MD -9.40 %; 95% CI -17.45 to -1.34) may also result in greater weight loss compared to LI/MT, but the evidence is very uncertain. A reduction in waist circumference at long-term follow-up (6 RCTs; n = 348) is likely higher after RYGB compared to LI/MT (MD -12.34 cm; 95% CI -17.88 to -6.81). OAGB (MD: -13.28 cm; 95% CI -22.04 to -4.53) and SG (MD-9.08 cm; 95% CI -15.74 to -2.43) may also lead to a higher reduction in waist circumference compared to LI/MT, but the evidence is very uncertain. The evidence is very uncertain about the effects of MBS procedures compared to LI/MT on long-term complete T2D remission (9 RCTs; n = 536). All MBS procedures (8 RCTs; n = 588) may result more often in partial T2D remissions than LI/MT, but the evidence is very uncertain. The evidence is very uncertain about the effect of all MBS procedures compared to LI/MT on SAE (9 RCTs; n = 598) and all-cause mortality in the long term (7 RCTs; n = 520). RYGB may reduce total long-term T2D complications compared to LI/MT (Rate ratio (RaR) 0.17; 95% CI 0.03 to 0.89; 5 RCTs; n = 356), but the evidence is very uncertain. Based on NMA results (10 RCTs; n = 612), RYGB may reduce HbA1c compared to LI/MT (MD -1.44%; 95% CI -2.26 to -0.63). OAGB (MD -2.01%; 95%CI -3.42 to -0.60) and SG (MD -1.01%; 95%CI -1.94 to -0.08) may also reduce HbA1c compared to LI/MT, but the evidence is every uncertain. Both RYGB and SG may increase mental and physical components of HRQoL compared to LI/MT (both 2 RCTs; n = 118), but evidence is very uncertain. The inclusion of cohort studies in the analyses of percentage weight loss, partial type 2 diabetes remission, SAE, and all-cause mortality confirmed the main findings. For most outcomes, the main reasons for downgrading certainty of evidence were related to risk of bias and imprecision. AUTHORS' CONCLUSIONS: In people with obesity and T2D, RYGB, OAGB and, to a lesser extent, SG may lead to long-term improvements in body weight, waist circumference, partial T2D remission, and HbA1c compared with LI/MT. However, due to imprecise results, the magnitude of the effects often remains uncertain or very uncertain. For other outcomes, especially complete T2D remission, SAE, all-cause mortality and T2D complications, the evidence is mainly very uncertain, due to a low numbers of participants and events. When interpreting these findings, it should be noted that cohort studies were not, as originally planned, included in the certainty of evidence assessment, as these studies were judged to have a high or critical risk of bias. Larger and well-designed studies may contribute to diminishing the existing uncertainties and enhancing our confidence in the findings. FUNDING: This Cochrane review was funded by the German Federal Ministry of Education and Research (BMBF) (grant number: 01KG2201). REGISTRATION: Protocol (2024) DOI: https://doi.org/10.1002/14651858.CD015622 PROSPERO ID: CRD42023457363.
Diabetes · ADA
Skeletal muscle insulin resistance is linked to lipid metabolism, yet whole-tissue analyses obscure how subcellular lipid remodeling contributes to metabolic dysfunction. We investigated whether Western diet induces compartment-specific changes in skeletal muscle lipid classes and fatty acid (FA) composition and how these relate to metabolic health. Western diet disrupts the relationship between lipids and metabolism. Diacylglycerol FA composition reflected dietary supply. Phospholipid remodeling was class and compartment specific. Lipid droplet-localized 1,3-diacylglycerol, phosphatidylethanolamine, and phosphatidylglycerol reflected muscle health. These results highlight subcellular lipid organization as a key determinant of muscle insulin resistance and provide a framework for identifying early lipid signatures relevant to human diabetes research.
Diabetes care · ADA
The International Diabetes Federation estimated that in 2024, 215 million adults-more than one-third of the global diabetes population-were living with diabetes within the Western Pacific Region (WPR), which includes nations with some of the highest prevalence worldwide. Rapid urbanization and economic development have profoundly reshaped lifestyles, which interact with biological predispositions resulting in an earlier onset of type 2 diabetes. These predispositions are not uniform across the heterogeneous populations within the WPR. Asian individuals tend to have a β-cell secretory failure phenotype with type 2 diabetes arising at lower adiposity, distinct from the high-adiposity phenotype with pronounced insulin resistance common among Pacific peoples. Improvements in diabetes care in high-income countries have reduced vascular complications and improved survival, shifting the clinical profile of individuals with type 2 diabetes toward an older population characterized by multimorbidity. In contrast, low-income settings continue to face a high prevalence of type 2 diabetes, compounded by limited access to medications and diagnostic tools, shortage of trained health care professionals, and other logistical barriers to care. In this diverse region where countries are at different stages of health care development, there are considerable opportunities for sharing of best practices through collaborative and translational research. These may include social and public health policies, health care delivery, use of registers to track disease patterns and care standards, and use of technologies to support self-management. For implementation of these actions, a major shift is required, toward prevention, capacity building, and demonstrating the impact of value-based prevention and data-driven care.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · AAO-HNS
OBJECTIVE: To estimate Bell's palsy incidence and evaluate the prevalence and associations with diabetes and other cardiometabolic conditions. STUDY DESIGN: Population-based cohort study. SETTING: Clalit Health Services, the largest healthcare provider organization in Israel (2005-2022). METHODS: Bell's palsy cases were identified by ICD-10 code G51.0 (n = 11,255). To optimize specificity, individuals with secondary facial palsy codes or competing acute etiologies within ±30 days were excluded. Members without Bell's palsy served as controls. Annual incidence per 100,000 person-years. Multivariable logistic regression adjusted for age, gender, socioeconomic status, and ethnicity; Bonferroni correction applied. Age-stratified and ≥40-year sensitivity analyses were performed. Systemic corticosteroid dispensing was evaluated in peri-index and extended capture windows. RESULTS: Among 5,489,298 members, 11,255 were diagnosed with Bell's palsy (median age, 51 years); about one-third occurred at ages 50 to 69 years. Incidence was ~18 per 100,000 person-years. Diabetes was more prevalent among cases than controls (21% vs 6%; standardized mean difference [SMD] = 0.45) and independently associated with Bell's palsy (adjusted odds ratio [aOR], 1.63), persisting across age groups and in the ≥40-year sensitivity analysis. Diabetic retinopathy and nephropathy were also associated (aOR 1.97 and 1.41). Stroke, smoking and obesity were also independently associated with Bell's palsy. Hypertension was more prevalent among cases but was not independently associated after Bonferroni correction and age-restricted analyses. CONCLUSION: Bell's palsy incidence remained stable throughout the 18-year study period and was associated with diabetes and diabetes-related complications. While current guidelines do not recommend routine HbA1c testing in patients with Bell's palsy, our findings support considering targeted diabetes screening and assessment of glycemic status and diabetes-related complications.
Diabetes care · ADA
Type 1 diabetes imposes a significant burden through morbidity, mortality, and high health care costs while also generating additional health, economic, and social costs, ranging from mental health conditions to risk of financial hardship to social stigma. Many of these outcomes may also spill over to families and caregivers. The economic literature increasingly recognizes the importance of including broader societal impacts in economic evaluations, including some guidelines for assessment of health interventions. However, in practice, societal impacts are incorporated in a limited way in assessments of type 1 diabetes therapies, most commonly through certain productivity-related measures, with limited consideration of broader impacts. In this article, we review the wider impacts of type 1 diabetes and examine how recent evaluations of novel technologies apply different perspectives. We find that economic assessments inconsistently incorporate broader societal impacts, such as psychosocial effects, informal caregiving, and long-term economic consequences. Consideration of a broader range of societal impacts may provide a more comprehensive evidence base for evaluating type 1 diabetes treatments and technologies, including in decisions related to their development, distribution, and reimbursement.
Diabetes · ADA
Childhood obesity shows large differences in body composition and health risk that are not well captured by BMI or simple metabolic classifications, prompting the need for more precise characterization. This study aimed to determine whether a data-driven framework integrating detailed body composition measures could better describe obesity-related phenotypic heterogeneity and its relationship with cardiometabolic risk in children. We delineated a continuous body composition manifold encompassing fat-dominant, lean-dominant, and concomitant high-mass phenotypes, which captured diverging cardiometabolic risk trajectories and yielded modest incremental improvements in risk prediction. These findings support more precise risk stratification and provide a practical tool to improve early identification and prevention of obesity-related health complications in children.
Diabetes care · ADA
OBJECTIVE: Many adults with type 1 diabetes (T1D) have overweight or obesity, underscoring the need for effective dietary weight loss strategies in this population. Time-restricted eating (TRE) has emerged as a popular approach for weight loss; however, its efficacy and safety in T1D have not been evaluated. We examined whether TRE is more effective for reducing body weight than standard care (daily calorie restriction [CR]), or compared with a control group, in adults with T1D and overweight or obesity. RESEARCH DESIGN AND METHODS: Participants were randomized to one of three groups for 6 months: 8-h TRE (eating only between 12:00 p.m. and 8:00 p.m., without calorie counting) versus CR (25% energy restriction daily), and compared with a no-intervention control group. The primary outcome was percent change in body weight by month 6. RESULTS: Thirty-two participants were randomized. By month 6, body weight did not change significantly in the TRE group (-2.19% [95% CI -5.70, -1.31]) or CR group (-0.47% [95% CI -4.72, 3.78]) relative to a control group, or between TRE and CR groups (-1.73% [95% CI -5.37, 1.92]). HbA1c levels were significantly reduced by the TRE group when compared with the CR group (-0.46% [95% CI -0.80, -0.12]). There were no significant differences in total insulin dose or mean glucose levels across groups. TRE did not increase the risk for diabetic ketoacidosis, severe hypoglycemia, or severe hyperglycemia. CONCLUSIONS: These findings suggest that TRE may be a safe approach for reducing HbA1c levels in T1D, although not more effective for weight loss compared with CR or a control group.
Diabetes care · ADA
OBJECTIVE: To identify and characterize daily and weekly patterns in glycemic management in longitudinal real-world continuous glucose monitoring (CGM) data from people with diabetes to enhance clinical interpretation and support more effective personalized diabetes management. RESEARCH DESIGN AND METHODS: This observational, retrospective study used two independent, multiyear, real-world CGM cohorts (T1DiabetesGranada and Connected Pen), comprising 86,779 participants with diabetes. Their mean age (SD) was 40.3 (15.8) and 44.0 (15.9), respectively, and there was a total of 21,011,021 measurement days. Weekly variations in CGM metrics and bolus insulin dose were examined using linear mixed-effects models, and daily temporal patterns were assessed. RESULTS: Weekly and daily glycemic patterns emerged. Mid-week time in range was consistently higher (e.g., Wednesday: +0.96 percentage points [%-points]; 95% CI 0.93-0.99; P < 0.001), with deterioration during weekends and Mondays (e.g., Sunday: -1.74%-points; 95% CI -1.77, -1.72; P < 0.001), mirrored by shifts in other CGM metrics. Bolus insulin dose increased on weekend days (e.g., Sunday: +0.69 units; 95% CI 0.64-0.74; P < 0.001). Daily analyses revealed distinct diurnal profiles, with the most favorable glycemic control during morning and midday hours on weekdays and consistently poorer control during evening and nighttime periods, particularly on weekends. CONCLUSIONS: Daily and weekly glycemic patterns revealed statistically robust and consistent temporal variations in glycemic control across two large real-world cohorts. Although the magnitude of these differences was small, the findings provide novel population-level evidence and underscore the value of longer-term CGM perspectives in routine care.
Diabetes · ADA
A rare loss-of-function variant in ZNRF3 (p.V228L) is enriched in individuals with obesity and is associated with increased subcutaneous white adipose tissue (sWAT) accumulation and lower fasting glucose levels. Both adipocyte-specific Znrf3 knockout and global variant knock-in impair sWAT browning, increase sWAT expansion, and improve glucose tolerance in mice. These findings establish ZNRF3 as a genetic regulator of fat distribution and thermogenic capacity, informing precise phenotyping of obesity. GWAS has implicated ZNRF3 in human fat distribution, yet its role in adipose tissue biology remains unknown.
JAMA
Diabetes care · ADA
OBJECTIVE: To examine incidence of long-term complications among people with childhood-onset type 1 diabetes, focusing on age at diabetes onset. RESEARCH DESIGN AND METHODS: A registry of children diagnosed with type 1 diabetes aged <16 years in New South Wales, Australia, between 1990 and 2009 linked to hospital, emergency department, public insurance, and death data from 2001 to 2019 to identify complications. Age at onset was categorized as <7 years, 7 to <13 years, and 13 to <16 years. Incidence rates and hazard ratios (HR), with 95% CI, for the risk of complications, were calculated from multivariable Cox regression models by 1) duration of diabetes 0 to <20 years and 2) attained age of 16-34 years, with HR adjusted for diagnosis year, sociodemographics, and acute diabetes complications. RESULTS: Of 5,202 people identified, 1,694 (32.6%) were diagnosed at age <7 years, 2,538 (48.8%) age 7 to <13 years, and 970 (18.6%) age 13 to <16 years. Within 20 years of onset, incidence ranged from 9.2 per 10,000 person-years (95% CI 7.2, 11.7) for cardiac complications to 53.4 per 10,000 person-years (95% CI 48.2, 59.0) for kidney complications. Diabetes onset at age <7 years (vs. 13 to <16 years) was associated with lower 20-year risk of complications, except lower-limb infections; cardiac adjusted HR (aHR) was 0.32 (95% CI 0.15, 0.66), severe retinopathy aHR was 0.25 (0.17, 0.36), lower-limb vascular complications aHR was 0.41 (0.24, 0.69), peripheral neuropathy aHR was 0.16 (0.08, 0.32), and kidney complications aHR was 0.40 (0.30, 0.53). Risk of complications did not differ by attained age. CONCLUSIONS: Children with type 1 diabetes onset at age <7 years had lower chronic complication risk in the first 20 years postdiagnosis, supporting a slower time to develop complications with prepubertal onset.
Diabetes care · ADA
OBJECTIVE: To assess the prevalence of housing instability and its associations with cost-related nonadherence and financial toxicity among adults with uncontrolled diabetes. RESEARCH DESIGN AND METHODS: We analyzed baseline randomized controlled trial data from 600 adults with uncontrolled diabetes and cost-related barriers to care. Logistic and linear regression assessed associations of housing instability with cost-related nonadherence and financial toxicity. RESULTS: Half (n = 298) reported housing instability, which was associated with greater odds of cost-related nonadherence (adjusted odds ratio 1.64; 95% CI 1.05, 2.56) and worse financial toxicity (B = -4.64; 95% CI -6.20, -3.09). Cost-related nonadherence was not significant after adjusting for diabetes distress and symptoms of depression and anxiety; financial toxicity remained significant. In sensitivity analyses, worry about housing costs, not housing or utility needs, was associated with financial toxicity. CONCLUSIONS: Housing instability was associated with financial toxicity and, in primary models, with cost-related nonadherence. Findings should be validated in longitudinal, nationally representative samples.
The Cochrane database of systematic reviews · Cochrane
RATIONALE: Obesity is a global public health issue and a major contributor to non-communicable diseases. In recent decades, the prevalence of obesity in adolescents has risen at an alarming rate. Although several systematic reviews have evaluated the effects of physical activity for the management of obesity in adolescents, key limitations remain in the literature, particularly in reporting completeness and the lack of standardised assessments of the certainty of evidence. OBJECTIVES: To synthesise evidence on the benefits and harms of physical activity interventions for the management of obesity in adolescents aged between 10 and 19 years. SEARCH METHODS: We searched various databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), and two trial registries, from 2012 to 4 December 2025. We applied no restrictions on language or publication status. We also searched grey literature sources. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that evaluated physical activity interventions lasting at least 12 weeks, of any frequency, type, or intensity, in adolescents aged 10 to 19 years with obesity (as defined by study investigators) at baseline. Eligible comparators included standard care, waiting list, no physical activity, or any other active interventions, such as a comparison of different physical activity parameters (duration, frequency, intensity). OUTCOMES: Critical outcomes: body weight, body mass index (BMI), BMI z-score, waist circumference, body fat percentage, glucose, and insulin resistance. Important outcomes: physical well-being, mental well-being, physical activity levels, overall quality of life, blood pressure, adiposity, lipid biomarkers, insulin, fasting glucose, mortality, adverse events, presence of obesity-related comorbidities or any non-communicable disease, disability, prevalence of obesity in adulthood, alterations in hunger, and access to health services. RISK OF BIAS: Pairs of review authors independently assessed the risk of bias in each included study using the original version of the Cochrane tool (RoB 1). SYNTHESIS METHODS: We synthesised results using meta-analysis when appropriate. Given the clinical and statistical heterogeneity, we predominantly used a random-effects model alongside sensitivity analyses. When meta-analysis was not feasible, we employed synthesis without meta-analysis (SWiM) methods. We assessed the certainty of the evidence using the GRADE approach. We grouped eligible comparisons into two broad categories: (1) physical activity intervention versus no-intervention control; and (2) one physical activity intervention versus another physical activity intervention or an active control. The first category is our main comparison. INCLUDED STUDIES: We included 30 studies (1508 participants) conducted across 15 countries, published between 2012 and 2023 (median year: 2017), with participants' ages ranging from 10 to 17 years. We assessed all included studies to be at high risk of bias. SYNTHESIS OF RESULTS: Physical activity intervention versus no-intervention control In adolescents with obesity aged 10 to 19 years, low-certainty evidence suggests that any form of physical activity may slightly improve the following outcomes compared to no intervention: body weight (mean difference (MD) -1.88 kg, 95% confidence interval (CI) -3.34 to -0.42; I= 47%; 17 studies, 749 participants); waist circumference (MD -2.88 cm, 95% CI -3.70 to -2.06; I= 0%; 10 studies, 476 participants); and body fat percentage (MD -2.96%, 95% CI -3.52 to -2.39; I= 10%; 9 studies, 313 participants). This review identified very low-certainty evidence regarding the effects of any form of physical activity on BMI (MD -1.38 kg/m², 95% CI -1.94 to -0.83; I= 43%; 16 studies, 537 participants), BMI z-score (MD 0.01 z-score units, 95% CI -0.34 to 0.37; I= 84%; 6 studies, 250 participants), glucose (MD -0.29 mmol/L, 95% CI -0.45 to -0.12; I= 76%; 7 studies, 299 participants), and insulin resistance (MD -0.99, 95% CI -1.25 to -0.73; I= 66%; 6 studies, 256 participants). Compared to no intervention, any form of physical activity may improve mental well-being, based on evidence from one study with 56 participants (self-perception: MD 0.22, 95% CI -0.10 to 0.54; self-efficacy: MD 0.58, 95% CI 0.21 to 0.95; self-esteem: MD 0.47, 95% CI 0.18 to 0.76). We identified low- or very low-certainty evidence for other important outcomes, including physical activity levels, blood pressure, other measures of adiposity and fat distribution, insulin and fasting glucose, and lipid biomarkers. The studies included in the main comparison did not report on the following important outcomes: physical well-being, overall quality of life, mortality, adverse events, comorbidities, disability, presence of obesity in adulthood, alterations in hunger or satiety, or access to health services. One physical activity intervention versus another physical activity intervention or active control All comparisons involving one type of physical activity versus another type (for example, high-intensity interval training versus moderate-intensity continuous training) or versus an active control group (such as participation in regular school physical activity programmes) were supported by very low-certainty evidence. Thus, the effects of the various types and levels of physical activity on the reported outcomes are uncertain. AUTHORS' CONCLUSIONS: Physical activity may improve health outcomes in adolescents with obesity, but the certainty of the evidence is low to very low. Serious methodological limitations, clinical and statistical heterogeneity, as well as small-study effects and imprecise results limited the certainty and interpretability of the current evidence base. Important knowledge gaps remain as none of the included studies enrolled adolescents with disabilities, the studies provided little information on contextual factors, and the amount of evidence hindered the analysis of relevant subgroups. Future high-quality, well-reported studies will likely change the review's conclusions. FUNDING: The Department of Nutrition and Food Safety at the World Health Organization (WHO) commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation, the Swedish International Development Cooperation Agency, the Government of the Grand Duchy of Luxembourg, and the Government of Germany to the Department of Nutrition and Food Safety. REGISTRATION: The full protocol was registered, and it is publicly available (https://osf.io/2wksa).
Journal of the American College of Cardiology · ACC
Diabetes care · ADA
OBJECTIVE: The association of gestational diabetes mellitus (GDM) subtypes with maternal cardiometabolic health is not known. We examined whether GDM subtypes were differentially associated with cardiometabolic health 10-14 years after delivery. RESEARCH DESIGN AND METHODS: We used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study. The exposure was GDM subtype (insulin deficient, insulin resistant, mixed defect, unclassified). The outcomes were prediabetes or diabetes and, secondarily, hypertension, dyslipidemia, metabolic syndrome, and predicted cardiovascular disease. RESULTS: Of 4,693 women, 3.0% had insulin-deficient, 9.0% insulin-resistant, 1.6% mixed-defect, and 0.7% unclassified GDM. Compared with no GDM, all GDM subtypes except unclassified were associated with higher risk of prediabetes or diabetes (adjusted risk ratios 2.14-2.88), metabolic syndrome, and predicted cardiovascular disease. Only insulin-resistant GDM was associated with dyslipidemia. CONCLUSIONS: All GDM subtypes were associated with an increased risk of prediabetes or diabetes, metabolic syndrome, and high predicted cardiovascular disease 10-14 years after delivery.
The New England journal of medicine
Nature
Sustained and controlled delivery of glucose-lowering agents using engineered designer cells is recognized as an effective strategy for diabetes therapy. However, current technologies rely on external signal control or have been programmed into mammalian cells using synthetic gene networks, which pose safety concerns arising from transplantation. Here we developed an engineered oral-deliverable glucose-sensing and functional response probiotic living drug for 'sense-and-respond'-based control of diabetic blood glucose. We created a glucose sensor based on a synthetic gene circuit that incorporates the glucose-responsive transcriptional regulator HexR, coupled with a synthetic promoter. Upon oral administration of the engineered probiotics carrying the sensor, the cells reside temporarily in the intestine and regulate the expression of therapeutic transgenes in response to glucose levels that exceed the normal threshold. We show efficacy from the engineered probiotics for glycaemic control in multiple diabetic mouse and non-human primate models, demonstrating that long-term oral administration drives clear improvements in lipid profiles, while also attenuating development of multiple diabetic complications. Our probiotics-based living drug enables therapeutic dosing in response to real-time blood glucose levels, providing a programmable, orally deliverable sense-and-respond platform for metabolic therapy without transplantation.
Journal of the American College of Cardiology · ACC
Nature
Diabetes · ADA
Accelerated brain aging has been reported in diabetes, but its links with diabetic peripheral neuropathy (DPN) and neuropathic pain remain unclear. We explored brain age gap (BAG) in type 1 diabetes to determine if it differs across neuropathic phenotypes, relates to clinical characteristics including DPN measures, and shows distinct regional patterns. Diabetes participants had 3.5 years of BAG, rising to 6-7 years in those with DPN. Diabetes duration was the main driver of BAG, whereas DPN had limited impact and neuropathic pain no clear contribution. BAG was widespread across the brain. Accelerated brain aging appears to affect people with diabetes regardless of neuropathic complications.
Showing 12 of 687 matching trials (5527 indexed).
NCT07222137
The purpose of this study is to find out if baricitinib can delay the onset of clinical type 1 diabetes (T1D) in people who are at high risk to develop T1D. Participation in the study will last up to approximately 5 years.
Diabetes Mellitus, Type 1
NCT07222332
The purpose of this study is to find out if baricitinib can preserve beta-cell function in participants newly diagnosed with type 1 diabetes. Participation in the study will last about 60 weeks.
Diabetes Mellitus, Type 1
NCT07595549
The purpose of this clinical study is to learn about the effects and safety of berobenatide (PF-08653944). This may help people with overweight or obesity lose weight. People in this study may also have type 2 diabetes. About 950 adults will be in this study. Berobenatide will be compared to a placebo. A placebo does not have any medicine in it but looks just like the medicine being studied. Berobenatide or placebo is given by a shot under the skin in the belly area. The objective of the study is to compare the experiences of people receiving berobenatide to those of the people who do not to assess if the study medicine is effective and safe. People will take part in this study for about 20 months. During this time, they will have about 15 study visits at the site. They will also have 2 study visits over the phone.
Obesity · Overweight and/or Obesity · Overweight
NCT07533175
The purpose of this clinical study is to find out if NNC0487-0111 is safe and effective for treating people who have excess body weight and type 2 diabetes. There are 2 study treatments in this study taken as injections under the skin once a week. Participants will either get NNC0487-0111 (the treatment being tested) or Placebo (treatment that has no active medicine in it). Which treatment participants get is decided by chance.
Diabetes Mellitus · Overweight · Obesity
NCT07434791
GOLD-STANDARD is a pragmatic, open-label pilot randomized controlled trial evaluating the feasibility, safety, and implementation of an early goal-directed Cardio-Kidney-Metabolic (CKM) care strategy compared with usual care in adults with type 2 diabetes and diabetic kidney disease who are at increased cardiovascular risk. Participants will be followed for 12 months to assess treatment uptake, adherence, retention, and safety outcomes, and to inform the design of a future definitive trial.
Diabetic Kidney Disease (DKD) · Type 2 Diabetes Mellitus (T2DM) · Chronic Kidney Disease
NCT07804849
Type 1 diabetes (T1D) in children involves autoimmune destruction of pancreatic ß- cells, leading to insulin deficiency. Verapamil is an L-type calcium channel blocker that has been used for decades to treat hypertension and certain cardiac conditions. Recent research has revealed its potential as a ß- cell-protective agent. Hence this study will evaluate the effect of once-daily oral verapamil on pancreatic ß- cell reserve , glycemic metrics and daily insulin requirements in children and adolescents with T1D.
Type 1 Diabetes Mellitus
NCT07803809
This study is a randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation phase I clinical trial aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of MWN105 injection in Chinese non-diabetic overweight or obese participants. The study plans to enroll 36 male and female participants. Three dose groups were preset, with 12 participants in each. They were randomly assigned to receive MWN105 injection or placebo at a ratio of 5:1 and were administered the treatment in a titration manner, once a week, with a dose increase every two weeks until reaching the target dose. The administration lasted for 8 weeks. The study consists of a 2-week screening period, an 8-week administration/observation period, and a 4-week follow-up period, totaling 14 weeks. The primary endpoint is the incidence of adverse events. Secondary endpoints include pharmacokinetics, pharmacodynamics, and immunogenicity.
Overweight , Obesity · Type 2 Diabetes Mellitus (T2DM) · MASH - Metabolic Dysfunction-Associated Steatohepatitis
NCT05933174
Sulfonylurea medications are unsafe for older patients with diabetes. They are associated not only with hypoglycemia, but also with falls and increased cardiovascular risk. Yet they continue to be prescribed frequently. Indeed, older adults with type 2 diabetes, who are especially prone to adverse effects, are more likely to be prescribed sulfonylureas than younger patients. This is unfortunate since over the past several years, newer, safer, and more effective classes of medications (GLP-1 agonists and SGLT2-inhibitors) have emerged. The investigators acknowledge that sulfonylureas are inexpensive and that their low cost is a driver of continued use. However, the investigators believe patients and providers should have discussions about the risks of sulfonylureas and safer and more effective alternatives, to make diabetes care safer overall in ambulatory settings. Our research is designed to promote such discussions. The investigators will first identify patients taking sulfonylureas regularly. Next, using recommendations from AHRQ and the Canadian Deprescribing Network, the investigators will empower patients to discuss their medications with their providers through a simple question prompt sheet. Patients will be divided into an intervention group which receives explicit prompting questions, and a control group that receives a general brochure on diabetes medications. Health care providers will receive education about newer diabetes medications through case-based discussions and academic detailing. Finally the investigators will measure key outcomes including the proportion of patients who have discussions about sulfonylureas and alternatives, rates of discontinuation, and measures of control of diabetes and associated cardiovascular risks. The investigators will also evaluate the experiences of patients and providers qualitatively through brief, semi-structured interviews. Should our multi-faceted, patient-oriented intervention prove effective in promoting discussions of sulfonylureas and alternatives, and also discontinuation of sulfonylureas and switching to newer alternatives, the investigators will incorporate our prompting questions into routine care for patients taking sulfonylureas. Our intervention can be easily disseminated to other settings and therefore has considerable potential to improve safety among patients with type 2 diabetes nationwide.
Type2diabetes
NCT07778121
Background: Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurrent collapse of the upper airway during sleep, resulting in intermittent hypoxia and fragmented sleep. The condition is more prevalent among individuals with hypertension, atrial fibrillation, type 2 diabetes, and other chronic diseases compared with the general population. Evidence indicates that untreated OSA is associated with adverse health outcomes, whereas treatment of OSA provides significant clinical benefits. However, a substantial proportion of individuals with OSA remain undiagnosed, highlighting the need to improve detection and reduce underdiagnosis. Devices currently used to diagnose OSA are not suitable for screening; however, newer alternatives may be appropriate. The study: This study is a pilot feasibility study. All participants will undergo an interview and examination at a baseline visit and will subsequently use OSA testing devices at home for three consecutive nights. The study includes a questionnaire assessing participants' experience with the devices and technology in general. The objective of this study is to test the feasibility of conducting a study in which adult participants with type 2 diabetes undergo three different home sleep apnea tests over three nights, including issues to be optimized in a subsequent main/definitive study. The main study aims to assess the diagnostic agreement between the devices and will be registered independently.
Type 2 Diabetes · Obstructive Sleep Apnea (OSA)
NCT07754461
This study aims to find out whether a study medicine called survodutide helps people control their blood sugar. Adults who live with type 2 diabetes and with a body mass index (BMI) of 23 kg/m2 or higher can join. The study has 3 parts. In each part the study compares survodutide with placebo. Survodutide is being developed to treat several health problems including type 2 diabetes. Placebo looks like survodutide but does not contain any medicine. Depending on a person's diabetes treatment, a person will be assigned either to * Part A: healthy eating and physical activity * Part B: diabetes tablets (no injection of insulin) * Part C: injection of insulin (with or without diabetes tablets) Participants are randomly put into 1 of 3 groups, which means the group is chosen by chance. Two groups of participants get survodutide at different dose levels, and the third group gets placebo as injection under the skin once a week. You have a 2 in 3 chance of getting survodutide. During the study, participants continue their regular diabetes treatment. Participants are in the study for about 1 year and 2 months. During this time, they attend up to 12 visits at the site and receive at least 9 phone calls. Study doctors regularly test participants' blood sugar by checking their HbA1c values and other laboratory test results. The study doctor also regularly checks participants' health and takes note of any changes. For each study part, the results will be compared between the survodutide and the placebo group to see whether the treatment works.
Type 2 Diabetes
NCT07778524
The goal of this study is to test a potentially easier method for measuring how much insulin a person is capable of producing than the current gold-standard method, the "hyperglycemic clamp." Participants will come in for a two-day (overnight) visit in which they will first undergo a "hyperglycemic clamp," in which they receive an intravenous (into the vein) infusion of glucose (sugar) in order to measure the maximum amount of insulin their body produces in response. They will then consume a series of three standardized meals throughout the rest of the day. At 23:00, they will take a single dose of alpelisib, a drug that interferes within insulin's actions in the body. Then, the following morning, they will undergo a "Mixed Meal Tolerance Test" in which they consume a standardized liquid nutritional beverage and have blood drawn periodically before and during the test.
Insulin Resistance · Type 2 Diabetes · Obesity & Overweight · Healthy Adult Participants
NCT05386719
This research study is being done to implement a screening program for prediabetes, diabetes, dyslipidemia and/or hyperlipidemia, and higher risk of cardiovascular disease in breast cancer survivors. This program will also help to direct individuals with risk factors to community and institutional resources for management.
Breast Cancer · Early-stage Breast Cancer
