Diabetes, Obesity & Metabolism最新文献

Aims: Prognostic markers for microvascular complications in type 1 diabetes are needed because factors beyond hyperglycaemia contribute to this risk. The triglyceride-glucose (TyG) index is an established marker of vascular complications in type 2 diabetes; however, its clinical significance in type 1 diabetes remains unknown. We aimed to investigate the association between the TyG index and long-term renal outcomes in a nationwide cohort of adults with type 1 diabetes.

Materials and methods: In this nationwide cohort study of 14 782 adults with type 1 diabetes from the Korean National Health Insurance Service database, we used Cox proportional hazards models to evaluate the risk of incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) across quartiles of the baseline TyG index during a median follow-up of 7.04 years.

Results: A significant dose-response relationship was observed between the TyG index and adverse renal outcomes. After multivariable adjustment, the highest TyG quartile (Q4) had a 2.15-fold (95% confidence interval, 1.87-2.48) and a 2.90-fold (95% confidence interval, 2.25-3.75) higher risk of developing CKD and ESRD, respectively, than the lowest quartile (Q1) (p for trend <0.001 for both). These associations remained significant in a competing-risk analysis that included all-cause mortality. Additionally, higher TyG quartiles were associated with a progressively worsening distribution of 5-year CKD stages.

Conclusions: The TyG index may serve as a valuable clinical indicator to identify individuals with type 1 diabetes at high risk for developing incident CKD and ESRD.

The kidneys play a vital role in maintaining systemic homeostasis by eliminating waste products, modulating metabolic homeostasis, and performing endocrine functions. Aging, characterized by hallmarks including oxidative stress, chronic inflammation, and metabolic dysregulation, constitutes a major predisposing factor for the pathogenesis of renal diseases. Amino acids serve as critical regulators of cellular metabolism, stress responses, and immune regulation, rendering amino acid metabolism intimately linked to the aging process. This review focuses on the multifaceted interplay between amino acid metabolism and renal aging, with particular emphasis on its implications in chronic kidney disease and related disorders: In senescent cells, accumulated branched-chain amino acids activate the mammalian target of rapamycin complex 1 (mTORC1), while tryptophan metabolites activate the aryl hydrocarbon receptor (AhR). Taurine deficiency impairs mitochondrial function and antioxidant defenses. Glutamine metabolism regulates the clearance of senescent cells through mechanisms including modulation of lysosomal pH and apoptosis. Glycine enhances glutathione synthesis and mitigates oxidative and inflammatory damage. In addition to modulating the aging process, urea cycle amino acids exhibit altered levels in kidney diseases and frequently serve as indicators of disease severity. Furthermore, we propose several promising therapeutic strategies, including nutritional interventions directed at specific amino acids and pharmacological therapies that target the modulation of amino acid metabolism. The relationship between amino acid availability and aging in kidney disease is not merely linear but involves a complex and dynamic interplay. Elucidating these mechanisms with advanced methods is key to developing novel clinical interventions and building a theoretical foundation for translational research.

Aims: MASLD, defined as a steatotic liver disease in the presence of one or more cardiometabolic risk factors and the absence of harmful alcohol intake, exhibits substantial heterogeneity complicating risk stratification. A prior clustering model proposed liver-specific and cardiometabolic subtypes, yet its generalizability and prognostic relevance remain unclear in the broader population. We aim to validate and replicate the prior approach in a nationally representative U.S.

Cohort:

Materials and methods: We included 3300 participants with MASLD from NHANES III. For validation, participants were assigned to previously defined clusters using published medoids. For replication, de novo clusters were derived using the Partitioning Around Medoids algorithm. Cox proportional hazards models accounting for the complex survey design of NHANES III were used to estimate hazard ratios for all-cause, cardiovascular-related, and diabetes-related mortality across clusters.

Results: Individual cluster assignments showed limited reproducibility between the validation and replication analyses, although the overall clustering pattern was preserved. Based on clinical profiles, clusters were categorized into cardiometabolic, liver-specific, and other subtypes. The cardiometabolic cluster consistently showed higher risks in both analyses, while the liver-specific cluster showed no significant associations.

Conclusions: The subtyping model demonstrated limited generalizability. Nonetheless, the consistent identification of broad cardiometabolic and liver-specific patterns suggests potential value for risk stratification, pending further validation.

Aims: Health-related quality of life (HRQoL) is a key patient-reported outcome in diabetes care, yet the extent to which somatic and psychological factors are associated with HRQoL remains unclear. This study examined how demographic, diabetes-related, medical, and psychological factors were independently associated with HRQoL in adults with diabetes.

Materials and methods: A cross-sectional online survey was conducted among adults with diabetes in Germany (September 2024-February 2025). HRQoL was assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). Participants also completed the PHQ-8 for depressive symptoms, the problem areas in diabetes (PAID) scale, and the hypoglycaemia fear survey (HFS-II). Clinical variables were self-reported and included diabetes type, duration, HbA1c, body mass index (BMI), and complications. Tobit regression accounted for the censored EQ-5D distribution. Blockwise multivariable models evaluated incremental explained variance across demographic, diabetes-related, comorbidity, and mental-health domains.

Results: Of 1581 invitees, 734 completed the EQ-5D (mean age 56 ± 14 years; 73% type I). In multivariable analyses, female sex (β = -0.045), higher BMI (β = -0.029), diabetic foot syndrome (β = -0.078), neuropathy (β = -0.123), and elevated depressive symptoms (β = -0.212), diabetes distress (β = -0.069), and fear of hypoglycaemia (β = -0.085) were all independently associated with lower EQ-5D utilities (p < 0.01). Mental-health variables explained a similar proportion of variance (≈22%) as diabetes-related complications (≈20%). Mental health factors like depression, diabetes distress, and fear of hypoglycaemia showed highly significant associations with reduced HRQoL by up to 27%.

Conclusions: Both diabetes complications and mental health determine HRQoL in people with diabetes. Depression emerged as the strongest independent predictor reducing HRQoL by up to 21%. This underscores the importance of mental health for HRQoL. This findings highlight the relevance of integrating mental health assessment into diabetes management.

Background: Efsubaglutide Alfa is a novel long-acting glucagon-like peptide-1 receptor agonist developed to promote weight loss and improve metabolic outcomes. This Phase 2a trial evaluated its efficacy, tolerability, safety, and pharmacokinetics (PK) in overweight and obese individuals unresponsive to lifestyle interventions.

Methods: In this multicenter, randomized, double-blind, placebo-controlled, multiple-ascending dose study, 50 participants were randomized (8:2) across five dose cohorts (5, 7.5, 10, 15, and 20 mg) or placebo. Participants received once-weekly subcutaneous injections of Efsubaglutide Alfa or placebo, with individualized dose escalation every 2 weeks, followed by 4 weeks at target doses. Primary endpoints were percentage change in body weight from baseline and the proportion achieving ≥5% weight loss. Secondary endpoints included changes in body composition and a metabolic composite index (BMI, waist circumference, blood pressure, lipid profiles). Tolerability, safety, immunogenicity, and PK were assessed.

Findings: Between 25 April 2024 and 18 November 2024, 50 individuals were randomly assigned. Mean baseline characteristics included age 36.3 years, bodyweight 92.9 kg, and BMI 33.0 kg/m². Efsubaglutide Alfa produced a mean weight reduction of 7.16% (95% CI: -8.08 to -6.24) versus 0.86% with placebo. Overall, 82.5% of Efsubaglutide-treated participants achieved ≥5% weight loss (vs. 0% placebo). Fat mass decreased by 4.47 kg, and lean mass also declined by 2.00 kg from baseline; however, the lean-to-fat mass ratio improved by 19.73 percentage points. BMI, waist circumference, and systolic blood pressure significantly decreased. Gastrointestinal adverse events were the most common, mostly mild to moderate, occurring primarily during dose escalation. No treatment-related serious adverse events occurred. Efsubaglutide Alfa showed dose-proportional PK.

Interpretation: Efsubaglutide Alfa demonstrated significant weight-loss efficacy, metabolic improvements, and a preferable tolerability and safety profile, supporting further clinical development for obesity and related metabolic disorders.

Aims: Insulin icodec, the first once-weekly basal insulin analogue, was approved in China in 2024. Although it has demonstrated robust clinical efficacy, its budget impact remains unknown, and the long-term cost-utility within the reimbursement context needs further estimates. This study evaluated the long-term cost-utility of once-weekly insulin icodec compared with once-daily insulin degludec in China.

Materials and methods: We used the validated IHE Diabetes Cohort Model to simulate lifetime costs and health outcomes for insulin-naive Chinese patients with type 2 diabetes, based on the Chinese subgroup of the ONWARDS 3 trial. The model incorporated diabetes-related microvascular and macrovascular complications, with a 40-year time horizon and 5% annual discount rate. Costs and utilities were derived from the 2024 national reimbursement drug list, the national insulin volume-based procurement policy, and published literature, expressed in 2024 US dollars. Analyses were conducted from the Chinese healthcare system perspective. Robustness was assessed through one-way and probabilistic sensitivity analyses. A complementary budget impact analysis (BIA) estimated national-level financial implications under different reimbursement scenarios.

Results: Compared with degludec, icodec increased life expectancy by 0.025 years and yielded a gain of 0.216 quality-adjusted life-years (QALYs), while reducing costs by $1450.73. One-way sensitivity analyses showed incremental QALYs ranging from 0.065 to 0.464 and cost savings from $ 265.84 to $4166.30. Probabilistic sensitivity analysis confirmed mean gains of 0.212 QALYs and cost reductions of $1320.46. The BIA estimates estimated annual savings of $1.17 million, $2.35 million, and $2.58 million in 2025, 2026, and 2027, following the reimbursement of icodec.

Conclusions: Within the current reimbursement context in China, once-weekly icodec is a dominant strategy compared with degludec, offering greater health benefits at a lower cost for patients with type 2 diabetes and generating potential annual savings.

Background: The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM).

Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID-19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age-adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program.

Results: Among 3 309 079 individuals aged 15-44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31-1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non-Hispanic Black individuals and non-Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups.

Conclusion: Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non-Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at-risk populations.

Lay summary: Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

Aims: To assess the real-world effectiveness of semaglutide versus tirzepatide in reducing major adverse cardiovascular events (MACE) among patients with overweight/obesity and established atherosclerotic cardiovascular disease (ASCVD) without diabetes in an insured US population.

Materials and methods: This retrospective, observational cohort study used Komodo Research Data and included patients ≥45 years of age with overweight/obesity and ≥1 claim for myocardial infarction (MI), ischemic stroke, or peripheral artery disease first treated with semaglutide or tirzepatide between 13/5/2022-31/1/2025. Propensity score matching was used to balance key baseline characteristics between cohorts. Primary outcomes included revised 3-point MACE (rMACE-3: MI, stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, coronary revascularization, hospitalisation for heart failure). Cox proportional hazard models were used to compare time to first event for study outcomes. A secondary per-protocol analysis was conducted where patients were censored at treatment discontinuation (gap in therapy >30 days).

Results: 10 625 patients were included in each matched cohort. Semaglutide was associated with statistically significant 29% (hazard ratio [HR] 0.71; p = 0.046) and 22% (HR 0.78; p = 0.040) reductions in the risk of rMACE-3 and rMACE-5, respectively, compared with tirzepatide. In the per-protocol analysis, semaglutide continued to be associated with a significantly lower risk of rMACE-3 (HR 0.43; p = 0.005) and rMACE-5 (HR 0.57; p = 0.003) compared with tirzepatide.

Conclusions: This real-world analysis of a large US claims database shows semaglutide was associated with early and significantly greater reductions in the risk of rMACE-3 and rMACE-5 versus tirzepatide among patients with overweight or obesity and ASCVD but without diabetes.

Objective: This observational study examined changes in mental health and wellbeing after 4-months liraglutide 3.0 mg treatment in patients with obesity and explored associations with weight loss.

Methods: We included 98 patients with obesity treated with liraglutide 3.0 mg. The Hospital Anxiety and Depression Scale (HADS: total score 0-42; depression/anxiety subscales 0-21), OBESI-Q psychological wellbeing (0-100) and anthropometrics were assessed at baseline and 4-month follow-up. Analyses included the full sample and subgroups with poor versus good baseline mental health.

Results: Body weight decreased after 4 months (-5.8%, p < 0.001). HADS total, depression, and (in trend) anxiety scores slightly decreased (-1.7 [95% confidence interval [CI] -3.2; -0.1, p < 0.05]; -1.0 [95% CI: -1.9; -0.1, p < 0.05] and -0.7 [95% CI: -1.5; 0.1, p = 0.095]). OBESI-Q psychological wellbeing scores increased (4.3 [95% CI: 0.8; 7.8, p < 0.05]). Mental health improvements occurred mainly in patients with poor baseline mental health. Weight loss occurred regardless of initial mental health. Anthropometrics changes were associated with changes in mental health and psychological wellbeing either significantly or in trend.

Conclusion: Liraglutide treatment was associated with weight loss without adverse mental health changes. Mental health benefits may be seen especially in those initially impaired. Weight loss was irrespective of baseline mental health status, suggesting liraglutide weight loss treatment effectiveness even in the presence of impaired mental health.

Obesity is a well-established risk factor for diabetes; however, its association with prediabetes remains controversial. Here, we aimed to assess the association between obesity and prediabetes risk. A systematic literature review was conducted using PubMed, Web of Science, Embase, Scopus, and Ovid through 3 May 2025, using keyword searches. We included cohort studies that assessed the association between anthropometric indices, specifically body mass index (BMI), waist circumference (WC), and prediabetes risk, operationalised as the development of prediabetes during the longitudinal investigation. We performed multiple meta-analyses assessing BMI and WC as continuous and categorical variables, including dose-response relationships with prediabetes risk. Of the 8434 records retrieved from the primary search, 28 were included in the meta-analysis. Considering BMI as both a continuous and a categorical variable indicated significant associations with prediabetes risk (risk ratio [RR]: 1.10 (95% CI: 1.03, 1.17) and RR: 1.52 (95% CI: 1.19, 1.94), respectively). The dose-response analysis confirmed a linear association between a 1-unit increase in BMI and a 4.6% increase in the risk of prediabetes. However, there was no significant association between WC and prediabetes risk either as a continuous or categorical variable. This study supports the use of BMI as a risk marker for prediabetes, whereas WC showed no significant association. While substantial heterogeneity and limited WC data warrant caution, the findings underscore the value of monitoring general obesity for early risk stratification and to prevent glycemic deterioration.