Diabetes, Obesity & Metabolism最新文献

Aims: Magnetic resonance imaging (MRI) provides the most accurate assessments of site-specific fat accumulation, but is not readily available. Less-accurate methods, such as Dual-energy x-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometry, have been widely used to measure overall and regional adiposity. However, the extent to which these approaches reflect MRI-derived fat depots is not fully understood.

Materials and methods: We included 18 622 White participants from the UK Biobank imaging visit. A total of 27 indices from DXA, BIA, and anthropometry were selected to characterise overall and regional adiposity, and all indices were standardised. In subgroups stratified by age and sex, Pearson correlation coefficients were used to assess the degree of linear association between these indices and MRI-determined subcutaneous, visceral, liver, and pancreas fat. Intraclass correlation coefficients (ICC) were further calculated to evaluate the absolute agreement between the corresponding fat measures.

Results: Generally, correlations of adiposity indices from DXA (total, trunk, android, gynoid, arm, and leg fat), BIA (total, trunk, arm, and leg fat), and anthropometry (body mass index (BMI), waist and hip circumference) with MRI measures were strongest for subcutaneous fat, followed by visceral fat, and weakest for liver and pancreas fat. The correlation coefficients with MRI-based visceral fat were larger for indices reflecting abdominal adiposity (e.g., DXA-based visceral, android, and trunk fat, BIA-based trunk fat, and waist circumference) and for measures of total adiposity (e.g., DXA- and BIA-derived total fat). The absolute agreement with MRI-based visceral fat was highest for DXA-based visceral, trunk, and android fat (ICC = 0.73-0.94), followed by waist circumference (ICC = 0.73-0.77), and then the remaining indices.

Conclusions: Indices of abdominal adiposity (as indicated by DXA-derived visceral, trunk, and android fat and waist circumference) appeared highly reflective of MRI-determined visceral fat. Considering cost and accessibility, waist circumference may serve as the most appropriate surrogate for assessing visceral fat.

Aims: Heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D) commonly coexist and are associated with poor outcomes. Although injectable semaglutide has demonstrated benefits in HFpEF, the effectiveness of oral semaglutide in this setting remains uncertain. This study compared all-cause death and hospitalisation between oral semaglutide and sitagliptin in patients with HFpEF and T2D.

Materials and methods: Using a global healthcare data and analytics platform, the TriNetX research network, we conducted a retrospective multi-centre observational study. We identified patients aged ≥18 years with HFpEF diagnosed before December 31, 2023 (N = 1 731 548), of whom 812 259 had concomitant T2D. Among them, 3470 initiated oral semaglutide and 22 840 initiated sitagliptin between October 1, 2019, and December 31, 2023. After propensity score matching, each group included 3452 patients. The primary outcome was all-cause death; the secondary outcome was hospitalisation.

Results: Over 1 year, the risk for all-cause death in patients who received oral semaglutide relative to those who received sitagliptin was significantly lower (4.3% [145/3452] vs. 7.0% [229/3452]; log-rank p < 0.001; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50 to 0.75). Similarly, patients who received oral semaglutide experienced fewer hospitalisations than those who received sitagliptin (37.1% vs. 42.4%; log-rank p < 0.001; HR, 0.83; 95% CI, 0.77 to 0.90).

Conclusions: Oral semaglutide appeared to be associated with a lower 1-year risk of all-cause death compared with sitagliptin in patients with HFpEF and T2D.

Aims: Imeglimin is a novel oral hypoglycemic agent approved for the treatment of type 2 diabetes in Japan, with dual actions to enhance insulin secretion and improve insulin sensitivity, suggested by preclinical evidence. However, the effect of imeglimin on tissue-specific insulin sensitivity and glucose kinetics using glucose tracers is unclear.

Materials and methods: In this single-arm intervention study, 22 Japanese men with type 2 diabetes received imeglimin 2000 mg/day for 20 weeks. Glucose metabolism and insulin secretion were assessed by the 75-g oral glucose tolerance test (OGTT) with double tracers at baseline, 1 week, and 20 weeks. Tissue-specific insulin sensitivity and insulin clearance were also evaluated in 16 participants using a two-step hyperinsulinemic-euglycemic clamp before and at 20 weeks. The primary endpoint was the change from baseline in the glucose area under the curve from 0 to 3 h (AUC_0-3h) during the OGTT at 20 weeks.

Results: The glucose AUC_0-3h during the OGTT was significantly decreased at 20 weeks of imeglimin administration (median change [interquartile range]: -108.63 [-148.25, -40.75] mg·h/dL, p = 0.0002). A similar reduction was already evident at 1 week. These reductions were mainly attributable to a decreased rate of oral glucose appearance. Insulin secretion indices were increased at 1 and 20 weeks. Clamp studies showed improved insulin sensitivity in skeletal muscle, liver, and adipose tissue, and increased insulin clearance.

Conclusions/interpretation: These results provide the first comprehensive evidence in humans that imeglimin improves insulin secretion and insulin sensitivity in multiple tissues.

Aims: To evaluate the glycaemic outcomes and safety of insulin glargine 300 U/mL (Gla-300) in Chinese people with uncontrolled type 2 diabetes (T2D) by baseline age and disease duration.

Materials and methods: INITIATION was a 24-week, interventional, single-arm study where adults with T2D (glycated haemoglobin [HbA1c] 7.5%-11.0%) received Gla-300. This post-hoc subgroup analysis assessed HbA1c change from baseline to week 24 (primary endpoint), other glycaemic endpoints, insulin dose, hypoglycaemia, body weight change, and treatment satisfaction (using the Diabetes Treatment Satisfaction Questionnaire [DTSQ]) by baseline age (<60 or ≥ 60 years) and disease duration (<5, ≥5 to <10 or ≥10 years in insulin-naïve participants, and <10, 10 to <15 or ≥15 years in those with prior basal insulin [BI]).

Results: Of 568 participants, 191 were insulin-naïve and 377 had received prior BI. Over 24 weeks, Gla-300 improved HbA1c in all age and disease duration subgroups. The least squares mean HbA1c change ranged from -1.02% (-11.1 mmol/mol) to -1.55% (-16.9 mmol/mol) in insulin-naïve participants and from -0.55% (-6.0 mmol/mol) to -0.76% (-8.3 mmol/mol) in prior BI participants. HbA1c <7.0% (<53 mmol/mol) achievement (ranging from 19.5% to 40.7%), other glycaemic endpoints, insulin dose increases, body weight changes and DTSQ score improvements did not significantly differ across the majority of subgroups, and the hypoglycaemia risk remained low.

Conclusions: Gla-300 improved glycaemic control with a low risk of hypoglycaemia in Chinese people with T2D across all ages and disease durations, including older individuals and those with long-standing diabetes.

Metformin remains the most widely prescribed drug for diabetes management, yet recent studies have explored additional benefits, whose mechanisms are not completely understood. Recent research has highlighted the central role of the intestine in mediating metformin's therapeutic effects, involving interactions with the gut microbiota, intestinal epithelial cells, and the immune system. Among its various properties, metformin also exhibits immunomodulatory activity, drawing growing attention to its impact on neutrophil function. In particular, the excessive formation of neutrophil extracellular traps (NETs) and the process of NETosis have been linked to diabetes and its complications. Emerging evidence suggests that NETosis is influenced by alterations in gut microbiota composition and may itself contribute to metabolic dysregulation. This review explores intestinal NETosis as a novel and promising target of metformin, emphasizing its potential therapeutic relevance and the need for further investigation. A deeper understanding of these molecular pathways is essential to explore new therapeutic applications, guide the development of more personalized therapies that minimize adverse effects, and inspire next-generation drugs that improve metformin's efficacy.

Background: Epidemiological studies have shown an association between obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the precise role of OSA in MASLD severity remains unclear. We aimed to evaluate the association of OSA with liver histological severity in Chinese bariatric surgery patients, especially metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis.

Methods: This prospective cross-sectional study enrolled 582 consecutive bariatric surgery patients. Key exclusions were other liver diseases, significant alcohol intake, and prior OSA treatment. All participants underwent preoperative polysomnography and intraoperative liver biopsy. Patients were stratified by biopsy-proven MASLD severity and OSA severity (apnea-hypopnea index, AHI). The primary outcomes were the associations of OSA with histologically defined MASH and significant fibrosis (stage ≥2).

Results: More severe MASLD subtypes exhibited higher AHI and greater hypoxia (p < 0.05). OSA severity was positively associated with histological features, including steatosis, ballooning, lobular inflammation, and fibrosis (all p < 0.05), as well as with higher NAFLD activity score (NAS) (p < 0.001) and MASH activity grade (p < 0.001). Multivariable analysis identified OSA as an independent predictor associated with histologically confirmed MASLD (odds ratio [OR] 1.86, 95% confidence interval [CI], 1.08-3.22), lobular inflammation (OR 95%CI, 1.18-2.79), MASH (OR 95%CI, 1.09-2.71), and significant fibrosis (OR 95%CI, 1.49-7.08). A linear dose-response relationship existed between AHI and both MASH and significant fibrosis (p < 0.05).

Conclusions: OSA is associated with more severe histological features of MASLD and contributes to the severity of MASH and significant fibrosis in patients with obesity.

Sex-based disparities in the incidence, prevalence and disease manifestations have been observed across various medical conditions, including type 1 diabetes (T1D). Differences in glycaemic control and quality of life between men and women have been reported, with women experiencing lower rates of glycaemic targets and a higher risk for long-term complications, particularly cardiovascular disease. Additionally, women face a greater economic and mental health burden related to T1D. This narrative review explores the challenges that complicate glycaemic management in women living with T1D, including hormonal influences during puberty, pregnancy and the (peri-) menopausal period. We also summarize current available evidence on the safety and efficacy of the MiniMed™ 780G (MM780G) system in addressing these challenges for women living with T1D. Finally, recent real-world data are reported on the absence of significant sex-related differences in glycaemic outcomes of over 280 000 real-world users of the MM780G, across various age groups from childhood and adolescence to the (peri-) menopausal period.

Aims: To determine whether the sequence of initiation between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) influences kidney outcomes in people with type 2 diabetes (T2D) receiving these therapies in association.

Materials and methods: We retrospectively included adults with T2D treated with both a SGLT2i and a GLP-1RA, stratified by treatment sequence: SGLT2i followed by GLP-1RA or GLP-1RA followed by SGLT2i. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from initiation of the first drug. Analyses used mixed models for repeated measures adjusted with inverse probability of treatment weighting (IPTW) and confirmed by propensity score matching (PSM).

Results: Among 565 participants (mean age 64 years, 29% women, diabetes duration 14 years, baseline eGFR 80 mL/min/1.73 m²), 210 initiated SGLT2i first and 355 GLP-1RA first. Over a median 4.3-year follow-up, eGFR declined more slowly in the SG group than in the GS group (adjusted difference 0.80 mL/min/1.73 m² per year; 95% CI 0.23-1.37; p = 0.006); this effect was more evident in patients with CKD at baseline. PSM analyses yielded consistent results. Changes in urine albumin-to-creatinine ratio, HbA1c, and body weight were similar between groups.

Conclusions: In people with T2D receiving combination therapy, initiating treatment with a SGLT2i was associated with greater long-term preservation of kidney function compared with starting with a GLP-1RA. Early SGLT2i use may confer better renal protection even when GLP-1RA intensification is subsequently required, confirming SGLT2i as a foundational therapy for preventing the decline in renal function in T2D.