Diabetes, Obesity & Metabolism最新文献

Aims: Obesity is a risk factor for multiple long-term conditions (MLTCs/multimorbidity). However, the impact of weight loss in people with MLTCs is unclear. We investigated the association between body mass index (BMI) change and the development of obesity-related complications (ORCs), as well as clinical and economic outcomes in individuals with obesity and MLTCs.

Materials and methods: This cohort study included adults aged ≤70 years with BMI ≥30 kg/m² and ≥2 ORCs. BMI was recorded during Years 1 and 4 of the baseline period. BMI change was categorised as increases or decreases of 3%-7%, 7%-15% and 15%-30%. Data were analysed using Cox regression (hazard ratios [HRs] for mental-health conditions, hospitalisation and mortality) and Ghosh-Lin models (risk of ≥1 new ORC and clinical consultations).

Results: A total of 618 426 individuals were included. The mean number of ORCs at index (Year 4) was 3.8 (standard deviation 1.5). HRs (95% confidence intervals) for incident ORCs were 0.96 (0.94-0.98), 0.98 (0.96-0.99) and 0.98 (0.97-0.99) for the highest to lowest BMI reductions, respectively; BMI increases were associated with HRs >1.00. Risk ratios for consultations were 0.99 (0.98-1.00), 0.99 (0.98-1.00) and 1.00 (0.99-1.00). BMI reductions were linked to lower polypharmacy rates. Both BMI decrease and increase were associated with higher HRs for mental-health conditions, hospitalisation and mortality versus stable BMI.

Conclusions: Weight loss in individuals with obesity and MLTCs was linked to both favourable and adverse outcomes, highlighting the importance of personalised treatment approaches that consider outcomes beyond weight loss.

Aims: The risk of diabetic nephropathy among patients with type 2 diabetes (T2D) can be reduced through optimal glycaemic control. It is not known if the pharmacological properties of long-acting insulin analogues may reduce the risk of diabetic complications compared with neutral protamine Hagedorn (NPH) insulin. We compared the risk of diabetic nephropathy associated with the use of long-acting insulin analogues with the use of intermediate-acting NPH insulin among patients with T2D.

Materials and methods: We conducted a retrospective cohort study using an active-comparator, new user design and the United Kingdom's Clinical Practice Research Datalink AURUM. Our primary outcome was incident diabetic nephropathy, and our secondary outcomes were chronic kidney disease (CKD) and end-stage renal disease (ESRD). We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each outcome associated with long-acting insulin analogues versus NPH insulin.

Results: The incidence rate (per 1000 person-years) of diabetic nephropathy was 16.3 (95% CI: 15.3-17.4) among initiators of long-acting insulin analogues and 17.5 (95% CI: 16.3-18.8) among initiators of NPH insulin. Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of diabetic nephropathy (adjusted HR: 0.94, 95% CI: 0.85-1.04). The adjusted HR was 0.91 (95% CI: 0.88-0.94) for CKD and 0.78 (95% CI: 0.46-1.32) for ESRD.

Conclusions: We did not find an association between use of a long-acting insulin analogue, compared with use of NPH insulin, and the risk of diabetic nephropathy among patients with T2D.

Aims: This study investigated changes in how people living with obesity (PwO) perceive weight-related discussions with healthcare professionals (HCPs) in Denmark from 2022 to 2024, a period marked by shifts in obesity treatment options as well as the broader understanding of obesity.

Materials and methods: A cross-sectional online survey was conducted among adult PwO in Denmark, building on the 2022 Awareness, Care, and Treatment In Obesity maNagement-Denmark survey with a few modifications. Data were collected via representative online panels from September to October 2024. Adjusted logistic regression models were performed.

Results: A total of 1005 PwO participated in the 2024 survey, compared to 879 in the 2022 survey. The proportion of PwO discussing weight with HCPs increased significantly from 38% in 2022 to 58% in 2024. The percentage of PwO reporting positive feelings after weight consultations did not change significantly. PwO in 2024 still refrained from discussing weight due to fear of prejudice (23%), previous negative experiences (17%) and the belief that reducing weight was their own responsibility (46%). Subgroup analyses in 2024 revealed that those currently using weight loss medications reported the most positive perceptions of weight-related discussions with their HCP.

Conclusions: Overall increased engagement of PwO regarding weight-related discussions with HCPs was observed from 2022 to 2024. However, barriers persist, since some PwO avoid interactions with HCPs due to previous experiences with stigma or the fear of being judged. Continued efforts are essential to address these barriers, enhance HCP education about weight-related bias, and foster a supportive environment for PwO in healthcare settings.

Aims: To evaluate the pharmacokinetics (PK) and safety of HR17031 (a fixed-ratio combination of INS068 and Noiiglutide) in subjects with hepatic impairment.

Materials and methods: This open-label, single-dose, nonrandomised, parallel-design trial enrolled 24 subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and normal hepatic function (n = 8 each). Participants received a single subcutaneous injection of HR17031 (10 U/0.024 mg). PK parameters of INS068 and Noiiglutide were determined by liquid chromatography-tandem mass spectrometry, free drug fractions were assessed by ultracentrifugation, and serum C-peptide concentrations were measured. Safety was monitored throughout.

Results: PK profiles of INS068 and Noiiglutide in subjects with mild hepatic impairment were comparable to those with normal function, while modest reductions were observed in moderate impairment (INS068 AUC_0-∞ geometric mean ratio [GMR]: 0.814 [0.703-0.944]; Noiiglutide AUC_0-∞ GMR: 0.713 [0.574-0.886]). Unbound fractions of both components and C-peptide concentrations showed no significant differences across groups. HR17031 was well tolerated, and there were no serious adverse events.

Conclusions: HR17031 demonstrated PK profiles of INS068 and Noiiglutide comparable between subjects with mild or moderate hepatic impairment and those with normal hepatic function, with modest reductions in moderate impairment. The treatment was well tolerated with a favourable safety profile, and no significant differences in C-peptide concentrations were observed across groups.

Aims: Metabolic syndrome (MS) is a heterogeneous condition associated with increased cardiovascular disease (CVD) risk. This study aimed to identify subgroups of individuals with MS using cluster analysis and to evaluate their differential risks for incident CVD events.

Materials and methods: Using UK Biobank data, we conducted a data-driven cluster analysis of drug-naïve individuals with MS (n = 62 776) and a control group without MS (n = 230 999). Separate clustering was performed for men and women using the following six variables: waist circumference; systolic and diastolic blood pressure (BP) values; triglyceride, high-density lipoprotein (HDL)-cholesterol, and fasting blood glucose values. Cox and logistic regression models were used to analyse the clusters in terms of their association with 3 point major adverse cardiovascular events (3P-MACE) (myocardial infarction, stroke, and CVD-related mortality).

Results: We identified three distinct MS subgroups with different risk profiles for 3P-MACE compared to the non-MS group. Cluster 1, characterised by the lowest HDL-cholesterol and highest triglyceride levels, had the lowest CVD risk among the MS clusters (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI] 1.30-1.46). Cluster 2 exhibited intermediate clinical and CVD risks (aHR 1.61; 95% CI 1.53-1.70). Cluster 3, characterised by the highest BP and fasting glucose levels, showed the highest CVD risk (aHR 1.87; 95% CI 1.74-2.00). This data-driven subtyping uncovered significant risk heterogeneity even within groups with the same number of MS criteria and was substantially more sensitive in identifying individuals with the highest-risk profile than the traditional counting method.

Conclusion: This clustering reveals clinical heterogeneity within the MS population. Identifying these subgroups provides a more nuanced approach to risk assessment than traditional criteria counting. This framework may help clinicians to better identify high-risk individuals who could benefit from more intensive monitoring and targeted management strategies.

Aims: The relationship between obesity phenotypes and cardiovascular disease (CVD) risk may be influenced by social determinants of health (SDOH), but evidence remains limited.

Materials and methods: This cohort study included 89 237 Chinese adults (mean age: 53.9 years; 39.0% male) free of CVD at baseline from the China PEACE Million Persons Project. Obesity phenotypes were defined by BMI and metabolic status. A composite SDOH index was used to classify participants into high and low burden groups. Cox proportional hazards models assessed the associations of obesity phenotypes with incident CVD, incorporating interaction terms to examine effect modification by SDOH.

Results: Over a median follow-up of 3.47 years (IQR: 2.57-4.28), 4999 incident CVD events (5.6%) were recorded. Compared with metabolically healthy normal weight individuals, metabolically unhealthy obese participants exhibited the highest CVD risk (HR: 1.75; 95% CI: 1.61-1.89). These associations were modified by SDOH burden, with stronger relative risks in the low SDOH burden group (P_interaction = 0.005). Joint analyses revealed that high SDOH burden further increased CVD risk across most phenotypes. The modifying effect of SDOH was more evident in older adults. Sensitivity analyses confirmed results robustness.

Conclusion: Obesity phenotypes were differentially associated with CVD risk, and these associations were shaped by social context. Individuals with lower SDOH burden may be more vulnerable to metabolic dysfunction. These findings highlight the need for prevention strategies that integrate both biological and social risk to improve CVD risk stratification.

Lay summary: This study followed nearly 90 000 adults in China to understand how obesity phenotypes and social determinants of health (SDOH)-such as education, income, and access to resources-interact to influence cardiovascular disease (CVD). Beyond confirming that metabolically unhealthy phenotypes carry greater CVD risk, the study demonstrated that these associations vary by SDOH burden, with stronger relative risks in favourable social conditions. Poor social conditions increased CVD risk across most obesity phenotypes, particularly among older adults.

Glucocorticoids (GCs) are widely utilised for the treatment of inflammatory and autoimmune conditions but often precipitate significant hyperglycaemia. People with type 1 diabetes (PWT1D) may be particularly affected due to the challenges of adjusting insulin dosing, for which recommendations remain unclear. Our aim is to synthesise the evidence on the glycaemic effects of GCs in PWT1D across various formulations, doses and administration routes, and to outline management strategies. In August 2025, a systematic search of MEDLINE, Embase and CENTRAL was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eligible studies included adult PWT1D exposed to GCs and reported glycaemic outcomes and/or management strategies. Twenty-two studies were included, comprising 368 PWT1D. GC exposure was consistently associated with marked hyperglycaemia and increased insulin requirements. Oral and intravenous GC regimens required substantial insulin dose escalation, in many cases up to 70% from baseline. During pregnancy, antenatal corticosteroids were best managed with structured subcutaneous or intravenous insulin protocols. Local injectable GCs caused delayed but prolonged excursions and required careful blood glucose (BG) monitoring. Emerging data suggest that automated-insulin delivery (AID) systems attenuate BG elevation but still require user intervention. Thus, GC therapy in PWT1D destabilises glycaemic management, though impact and timing vary by formulation, dose, administration route, patient-specific factors and clinical context. Proactive, individualised insulin adjustments aligned with GC pharmacokinetics and frequent BG monitoring or continuous glucose monitor use represent the most practical current strategy. Further research is required to develop evidence-based guidelines and to clarify the role of AID.

Overweight or obese women with polycystic ovary syndrome (PCOS) frequently exhibit metabolic disturbances and reproductive dysfunction. This systematic review and meta-analysis evaluated the efficacy and safety of liraglutide in improving metabolic and reproductive outcomes in this population. PubMed, Embase, the Cochrane Library, Scopus, Web of Science and ClinicalTrials.gov were systematically searched from inception to 31 May 2025 for randomized controlled trials (RCTs) comparing liraglutide (alone or in combination) with placebo, metformin or non-liraglutide active treatments in overweight or obese women with PCOS. Two reviewers independently conducted study selection, data extraction and risk-of-bias assessment. Pooled analyses were performed using a random-effects model, and results were expressed as Hedges' g or odds ratios (ORs) with 95% confidence intervals (CIs). Seven RCTs comprising 330 women with PCOS were included. Compared with control treatments, liraglutide significantly increased menstrual frequency (g = 1.76; 95% CI [0.28, 3.24]), reduced body mass index (BMI; g = -0.52; [-0.94, -0.10]) and improved insulin resistance (homeostatic model assessment of insulin resistance; g = -0.52; [-0.83, -0.22]), lowered luteinizing hormone and free androgen index and modestly increased sex hormone-binding globulin levels. Heterogeneity was high for menstrual frequency. Reproductive outcomes such as ovulation and pregnancy could not be pooled due to insufficient reporting. Liraglutide was generally well tolerated, with adverse events consisting mainly of mild gastrointestinal symptoms. Liraglutide therapy improved BMI, insulin sensitivity and menstrual regularity in overweight or obese women with PCOS, suggesting concurrent metabolic and reproductive benefits. However, larger and longer-term trials are warranted to validate its reproductive efficacy and safety profile.