Diabetes, Obesity & Metabolism最新文献

Objective: This study aimed to develop and validate a health-economic model incorporating glycaemic variability to support the economic evaluation of novel interventions.

Methods: We developed a Monte Carlo-based Markov model, primarily using data from the United Kingdom Prospective Diabetes Study. An innovative glycaemic variability module was constructed, with its key parameter being the time in range (TIR). TIR was defined as the percentage of time a patient's glucose level remained within the target range of 3.9-10.0 mmol/L. The module was parameterized based on quantitative clinical evidence. The base model underwent face, internal, and external validation, with performance assessed using the R², root mean square percentage error (RMSPE) and symmetric mean absolute percentage error (SMAPE). To evaluate the structural uncertainty introduced by the new module, we conducted an exploratory scenario analysis in which the incremental improvement in TIR was modelled from 0% to 100%.

Results: The model showed good overall reliability. Specifically, face validity was confirmed, while internal and external validation both demonstrated R² values exceeding 0.95. For the internal and external validation, the RMSPE was 0.328 and 0.347, and the corresponding SMAPE values were 0.175 and 0.279, respectively. The exploratory scenario analysis supported the structural validity of the module. Over the first decade, the cumulative incidence of background retinopathy, microalbuminuria, peripheral vascular disease, and mortality decreased as TIR improved. However, the incidence gaps narrowed in the long run, which was consistent with clinical observations.

Conclusion: This study developed and validated a health-economic model incorporating glycaemic variability, which provides a potentially robust tool to inform economic evaluations of novel interventions.

Aim: To assess the application of current waist-to-height ratio (WHtR) and waist circumference (WC) evaluation criteria and identify preferred recommendations for public health practise.

Materials and methods: Data were from three waves of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted in 2010, 2014 and 2019; abdominal obesity was classified using four WHtR and WC standards. Age- and sex-specific WHtR and WC percentile curves were generated using the LMS method. Prevalence of central adiposity by WHtR/WC and general obesity by BMI were compared. Predictive performance of the criteria was validated using an independent dataset with cardiometabolic risk factors.

Results: WHtR percentile curves showed a relatively flat trend with age in both sexes compared to WC curves. Abdominal obesity prevalence increased significantly from 2010 to 2019 across all criteria: international cut-off (0.46) (21.26%-27.66%), Chinese WC cut-offs (13.77%-19.64%), international WHtR cut-off (0.50) (9.12%-13.01%) and international WC cut-offs (7.95%-11.95%). All abdominal obesity criteria identified substantially more cases than BMI-based general obesity in 2019 (8.14%). The Chinese WC cut-offs showed superior predictive performance compared to the other three standards for cardiometabolic outcomes.

Conclusions: The Chinese WC cut-offs and international cut-off (0.50) are optimal for childhood abdominal obesity screening in China due to their public health applicability. Standardized global criteria are urgently needed to enhance research comparability.

Aims: Once-weekly (OW) insulins represent a promising strategy to reduce injection burden and improve adherence in type 2 diabetes management. This meta-analysis aimed to quantify pooled effect sizes for key biological and clinical outcomes, integrating new findings from the five large trials published in 2025.

Materials and methods: We systematically searched PubMed, WoS, ClinicalTrials.gov and EU Clinical Trials databases up to June 2025 for randomized controlled trials (RCTs) evaluating OW insulins in type 2 diabetes. Primary outcomes included efficacy (HbA1c, fasting plasma glucose (FPG), time-in-range (TIR), time-above-range) and safety outcomes (body weight, hypoglycaemia, time-below-range). Data were analysed using both frequentist and Bayesian approaches.

Results: Among 435 screened records, 16 RCTs were included. OW insulins achieved a greater reduction in HbA1c compared to once-daily insulin or semaglutide (pooled mean difference: -0.12%, 95% CI: -0.19 to -0.04, p = 0.007). TIR was significantly longer in the OW insulin group (+2.41% of total time, 95% CI: 1.13 to 3.69, p = 0.002), while FPG changes were comparable (-3.37 mg/dL, 95% CI: -7.95 to 1.21 mg/dL, p = 0.14). Body weight changes were generally similar, but excluding trials using IcoSema revealed a modest weight gain (+0.33 kg, 95% CI: 0.04 to 0.62, p = 0.030). The incidence of clinically significant or severe hypoglycaemia did not differ between groups (pooled incidence rate ratio: 1.04, 95% CI: 0.79 to 1.28, p = 0.75). Meta-regression confirmed consistent effect sizes across OW insulin types, treatment durations and prior insulin regimens.

Conclusions: OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur.

Aims: Randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors have yielded inconsistent findings regarding mortality benefits. It remains unclear whether, and in which subgroups, SGLT2 inhibitors confer survival benefits in older adults with diabetic kidney disease (DKD).

Materials and methods: We emulated a target trial using a nationwide claims and health checkup database in Japan to compare all-cause mortality between SGLT2 and dipeptidyl peptidase-4 (DPP4) inhibitor initiators among 5371 adults aged ≥65 years with DKD. The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated using propensity score overlap weighting and Cox proportional hazards models in an intention-to-treat analysis. A per-protocol analysis with inverse probability of censoring weighting was conducted as sensitivity analysis. Effect modification by age, body mass index (BMI) and Charlson comorbidity index (CCI) was assessed using restricted cubic spline models.

Results: During a median follow-up of 2.23 (IQR, 1.07-3.49) years, 437 deaths occurred. SGLT2 inhibitor use was associated with significantly lower all-cause mortality than DPP4 inhibitors (HR, 0.51; 95% confidence interval, 0.38-0.70), with consistent results in the per-protocol analysis (HR, 0.50; 95% confidence interval, 0.35-0.73). Survival benefit was evident up to about 80 years of age and among individuals with BMI ≥22 kg/m², irrespective of CCI.

Conclusions: In this target trial emulation study, SGLT2 inhibitors were associated with lower mortality in older adults with DKD, particularly those under 80 years and with BMI ≥22 kg/m². These findings support personalized treatment decisions for this high-risk population in clinical practice.

Background and aims: Methylglyoxal-derived hydroimidazolone (MG-H1), one of the advanced glycation end-products (AGEs), has been a potential biomarker of type 2 diabetes (T2DM), which is strongly related to insulin resistance. However, the relationship between the dynamics of MG-H1 and insulin resistance has not been characterized, and its mechanism on insulin resistance is unknown. In this study, we aimed to investigate the relationship between MG-H1 and insulin resistance in the clinical study of Japanese individuals and identify the molecular mechanisms underlying MG-H1 associated phenomena in vitro.

Methods: We performed the meal tolerance test (MTT) and hyper-insulinemic-euglycemic clamp analysis in 19 patients with T2DM and 19 participants without diabetes (non-DM). We measured their fasting and postprandial MG-H1 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the effects of MG-H1 on glucose uptake and insulin signalling in C2C12 skeletal myocytes.

Results: The postprandial MG-H1 and the area under the curve (AUC) of MG-H1 in MTTs were significantly negatively correlated with the glucose disposal rate (GDR) in clamp studies both in the T2DM (r = -0.72 [p < 0.001]) and non-DM (r = -0.54 [p < 0.05]) groups. In cultured C2C12 skeletal myocytes, pre-treatment with MG-H1 inhibited insulin-stimulated phosphorylation of Akt and glucose uptake, via the activation of mechanistic target of rapamycin complex 2 (mTORC2).

Conclusions: In clinical study findings revealed that postprandial MG-H1 was a novel marker of insulin resistance in Japanese individuals, and in vitro findings using cultured C2C12 skeletal myocytes suggested that MG-H1 disturbs insulin signalling via the mechanisms of mTORC2 activation.

Background: Effective anti-obesity interventions that preserve lean mass are of increasing clinical significance for optimizing metabolic health. This study investigated whether lorcaserin, a centrally acting weight loss agent, modifies body composition, circulating lipidomic profiles, and muscle-regulating hormones within the myostatin-activin-follistatin-IGF-1 (MAFI) axes.

Methods: Forty-eight adults with obesity were randomized to lorcaserin (10 mg twice daily) or placebo for 6 months in a double-blind trial. Regional body composition, hormones and lipidomics were assessed. Changes were analysed using linear mixed models with fixed effects for time, treatment and interaction. Adjusted deltas and endpoints were compared by analysis of covariance controlling for baseline body mass index. Lipidomic profiles were analysed using principal component and partial least-squares discriminant analyses.

Results: Lorcaserin reduced total body weight (time*treatment, p = 0.004). Adjusted delta and endpoint comparisons showed reductions in total body (p = 0.031) and abdominal fat mass (p = 0.002). Lipidomic assessments revealed primarily lower levels of triglyceride-rich lipoproteins with treatment. No significant changes in MAFI axes components were detected in linear mixed models.

Conclusions: Lorcaserin treatment was associated with greater abdominal fat mass loss, favourable lipid profile changes, while MAFI components remained largely unaffected. Lorcaserin may improve cardiometabolic health primarily through reductions in central adiposity.

Aims: To evaluate the association between longitudinal non-HDL-C exposure and the risks of major adverse cardiovascular events (MACEs) and all-cause mortality in type 2 diabetes patients on lipid-lowering therapy.

Materials and methods: This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial included patients with type 2 diabetes who had non-HDL-C measured at baseline and four subsequent visits over 24 months. Longitudinal exposure was assessed using cumulative load, variability (standard deviation) and trajectory (slope). Outcomes were MACEs and all-cause mortality. Cox proportional hazard models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among 4673 participants with a median follow-up of 7.5 years, 695 MACEs and 842 deaths occurred. After adjusting for baseline and mean non-HDL-C levels, the highest quartile of cumulative load (HR, 1.81; 95% CI, 1.41-2.32), variability (HR, 1.27; 95% CI, 1.00-1.60) and the most rapidly increasing slope (HR, 1.26; 95% CI, 1.02-1.56) were each associated with increased risks of MACEs, compared to the lowest quartile. The association with all-cause mortality followed a similar pattern, except for the non-HDL-C slope. Stratified analyses showed that cumulative load and variability were associated with MACEs among participants with baseline non-HDL-C < 130 mg/dL, and with all-cause mortality among those with baseline ≥130 mg/dL. No significant associations with slope were observed within strata of baseline non-HDL-C.

Conclusions: Longitudinal non-HDL-C exposure showed associations with both MACEs and mortality, independent of baseline non-HDL-C, underscoring the need for sustained and stable non-HDL-C control over time.

Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity. It usually results in spectacular weight loss, associated with improvements of obesity-associated comorbidities. The mechanisms underlying these benefits are not fully understood but could involve a postoperative activation of the enzyme 5' AMP-activated protein kinase (AMPK). Hence, as AMPK is largely expressed in insulin-sensitive cells, it acts as a key regulator of cardio-metabolic homeostasis, and its activity is down-regulated in tissues from obese, insulin resistant patients. This narrative review aims to summarise the available clinical data regarding changes in AMPK activity following MBS and to discuss the potential relevance of these changes in postoperative physiology. The eight studies reporting specifically changes in AMPK activity following MBS in humans were analysed. They all showed increases in AMPK activity in tissues or blood cells, with effects observed as early as 3 months and persisting beyond 12 months post-surgery. However, the data does not allow us to conclude on (i) the potential specificity of effects depending on the surgery procedure, (ii) the mechanisms involved in the AMPK activation, and (iii) its role in postoperative metabolic outcomes, highlighting that further investigations are warranted to address these issues. Understanding AMPK changes in postoperative physiology could establish its relevance as a potential prognostic marker of surgery metabolic outcomes and as a new target to improve the benefits of MBS. More generally, it may provide insights into the development of novel therapeutic strategies for obesity and associated comorbidities.