Aims There is uncertainty whether traditional glycemic metrics remain associated with long-term outcomes among patients with type 2 diabetes who achieve recommended continuous glucose monitoring (CGM) targets. This study was aimed to investigate the association of glycated albumin (GA) and ratio of glucose management indicator to GA (GMI/GA) with risks of all-cause mortality in type 2 diabetes achieving CGM targets. Materials and Methods A total of 3482 patients with type 2 diabetes who met CGM targets, defined as time in range (TIR) >70%, time below range (TBR<3.9) <4%, and time above range (TAR(>10.0)) <25%, were included in the cohort study. Cox proportional hazards models and restricted cubic spline were used to evaluate associations of GA and GMI/GA with mortality. Results During a median follow-up of 11.0 years, 514 patients (14.8%) died. GA exhibited significant linear positive association with risks of all-cause mortality, and the highest GA quartile had 34% increased risk (HR = 1.34, 95% CI 1.01-1.78). Conversely, GMI/GA ratio showed significant non-linear association (p for nonlinearity = 0.042). Compared with the reference third quartile (0.36-0.40), participants in the lowest quartile (<0.30) had 40% higher risk of all-cause mortality (HR = 1.40, 95% CI 1.10-1.80). Conclusion Among patients achieving CGM targets, elevated GA and lower GMI/GA were associated with higher risks of all-cause mortality. These findings suggest that traditional glycemic metrics may complement CGM metrics in the assessment of long-term risks.
AIMS:The purpose of this paper is to compare the risk of incident type 2 diabetes mellitus (T2DM) among patients with hyperlipidaemia treated with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors versus statins and other nonstatin lipid-lowering agents. METHODS AND RESULTS:This target trial emulation study used a retrospective, propensity score-matched cohort design based on the TriNetX Global Collaborative Network. Adults (≥ 18 years) with hyperlipidaemia diagnosed between January 2015 and December 2024 were included. Patients with preexisting diabetes, malignancy, or death during follow-up were excluded. Three active-comparator analyses compared PCSK9 inhibitors with statins, ezetimibe and fenofibrates under a per-protocol framework. Propensity score matching (1:1) balanced demographics, comorbidities, BMI, lipid profiles and healthcare utilization. Incident T2DM was identified using ICD-10 codes and analysed. Multiple sensitivity analyses including intention-to-treat analysis were performed. In the main analysis model, PCSK9 inhibitor use was associated with a significantly lower risk of incident T2DM than statins (HR 0.815; 95% CI 0.764-0.869), ezetimibe (HR 0.919, 95% CI 0.867-0.974), and fenofibrates (HR 0.517; 95% CI 0.493-0.542). Findings were consistent across subgroups and sensitivity analyses. No significant difference was observed between different PCSK9 inhibitor modalities. CONCLUSIONS:In this large-scale real-world cohort, PCSK9 inhibitors were associated with a lower risk of new-onset T2DM compared with other lipid-lowering therapies, supporting their metabolic safety and clinical use in patients at risk for diabetes.
AIM:The purpose of this paper is to examine the acute and nocturnal glycaemic response to morning fasted, fed or afternoon fed resistance exercise in people with type 1 diabetes. METHODS:In a crossover RCT, people with type 1 diabetes performed three acute bouts of resistance exercise in (1) morning (8 AM-10:30 AM) in a fed state, (2) morning (8 AM-10:30 AM) in a fasted state and (3) afternoon (3-8 PM) in a fed state, with interstitial glucose levels measured 6-h post-exercise and in the nocturnal period (11 PM-6 AM). RESULTS:In all participants (n = 66), mean glucose levels were lower in the 6-h period after afternoon fed versus morning fasted resistance exercise (9.46 ± 2.56 vs. 8.65 ± 2.04 mmol/L, P = 0.04), with no other differences noted. In multiple daily injections (MDI), users (n = 47), but not insulin pump users (n = 19), in the 6-h period post-exercise mean glucose levels were higher (9.63 ± 2.58 vs. 8.44 ± 1.93 mmol/L, P = 0.007), time-in-range (3.9-10.0 mmol/L) lower (50.9 ± 29.5% vs. 67.0 ± 27.6%, P = 0.007) and time above range (> 10.0 mmol/L) higher (44.4 ± 32.1% vs. 26.3 ± 25.3%, P = 0.003) in morning fasted versus afternoon fed state; no other differences were noted. CONCLUSION:Resistance exercise timing and feeding status (fed vs. fasted) independently influence post-exercise glycaemic responses in people with type 1 diabetes. Performing resistance exercise in the afternoon under fed conditions was associated with a more favourable glucose profile, particularly among MDI users. These findings indicate that consideration of both time of day and feeding status is important when optimising resistance exercise prescription in this population. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT05884814 (Registered on 10 May 2023).
BACKGROUND:The aryl hydrocarbon receptor (AhR) is linked to inflammation, but its plasma agonist activity and association with metabolic and inflammatory markers in obesity remain unclear. This cross-sectional study aimed to determine the level of plasma AhR agonistic activity and its association with systemic inflammation and metabolic dysregulation in obesity. METHODS:Plasma samples were collected from 80 non-diabetic (39-obese, 23-overweight, and 18-normal/healthy weight) individuals. AhR agonist activity was assessed using a cell-based luciferase reporter assay. Plasma AhR was quantified by ELISA. Inflammatory markers were assessed using a multiplex Luminex platform. RESULTS:Our findings indicate that plasma AhR agonist activity is elevated in obese (92.77 ± 4.002 fold activation) compared with normal/healthy weight (51.39 ± 2.335) and overweight participants (67.54 ± 5.24 fold activation). Moreover, the AhR protein was also elevated in obese (94.88 ± 7.62 pg/ml) compared to normal/healthy weight (65.88 ± 6.78 pg/ml) and overweight participants (67.54 ± 5.24 pg/ml), which was positively correlated with AhR activity (r = 0.441, p < 0.0001). AhR activity was positively correlated with inflammatory markers including IL-1β, IL-6, TNF-α, TNF-β, and MCP-1, as well as metabolic markers such as BMI, total cholesterol, TG, insulin, FBG, and HbA1c. In contrast, it was negatively associated with HDL cholesterol. Notably, HOMA-IR was positively correlated with AhR activity. In the regression model, TNF-α, MCP-1, BMI, and HDL cholesterol emerged as significant predictors of AhR activity. CONCLUSIONS:Our findings demonstrate that elevated plasma AhR agonist activity is associated with obesity, systemic inflammation, and metabolic dysregulation. These results highlight AhR activity as a biomarker of interest and support further studies to clarify its mechanistic role and potential clinical relevance in metabolic disorders.
BACKGROUND:Diabetes and its risk factors are embedded in a complex multilevel ecology. Upstream factors (i.e., 'forcing factors' that refer to fundamental population-based social, economic, and political structures shaping health outcomes long before disease develops) and downstream risk factors (i.e., the individual-level characteristics and outcomes that result from upstream forcing factors) are to be considered when predicting diabetes. This study aims to predict diabetes prevalence at the United States' (US) county level using analytical methods that account for the contextual complexity of diabetes. METHODS:US county-level datasets incorporating 27 predictor variables were analysed cross-sectionally. A Light Gradient Boosting Machine (LightGBM) model was trained to predict county-level diabetes prevalence, after which model performance and feature importance were evaluated. FINDINGS:The final model retained 17 features and explained 95% (R2 = 0.952) of the variance in county-level diabetes prevalence. Physical inactivity, racial and ethnic minority status, frequent physical distress, and obesity showed the highest Shapley (SHAP) importance values, which exceeded all remaining SHAP values. INTERPRETATION:This study delineates the most important predictors of diabetes prevalence based on a complex multilevel ecology. Efforts to reduce diabetes prevalence should address both upstream and downstream risk factors emphasising physical activity, obesity, equity, and cultural considerations.
AIMS:We aimed to determine whether muscular fitness, focussing on power-related components, is reduced in adults with type 1 diabetes (T1D) compared with the group without T1D. METHODS:Adults with T1D and healthy controls were enroled in the study. Muscular fitness was evaluated using Handgrip strength (HG), knee extensor isometric maximal torque (PeakT), and 10-repetition sit-to-stand (STS). Moreover, the specific power index of the lower limb was obtained from the ratio between STS and skeletal muscle mass. RESULTS:Sixty-seven individuals with T1D (32 females, 35 males; age: 38.9 ± 14.6 years) were matched for age, sex, body mass index and physical activity level with a non-diabetic Control Group (CG, n = 67). The T1D group was significantly slower than the control group (CG) during the STS test (20.2 ± 3.8 vs. 18.6 ± 3.3 s, p < 0.01) and exhibited a lower specific power (5.3 ± 1.2 vs. 5.9 ± 1.3 W/kg, p < 0.01). No significant differences were observed in HG and PeakT (p > 0.05) between the T1D and CG groups. CONCLUSIONS:Adults with T1D show a reduction in dynamic muscle function (STS), whereas isometric function appears to be preserved.
AIMS:The clinical effectiveness of antibiotic (ATB) therapy in patients with infected diabetic foot ulcers (iDFUs) depends on achieving sufficient ATB concentrations in both serum and peripheral tissues. This study evaluated the availability and bactericidal activity of the time-dependent ATBs-ceftazidime (CTZ) and amoxicillin/clavulanate (AMC) in serum and peripheral tissues by comparing bolus versus continuous administration. METHODS:Sixty patients with iDFUs were randomised into four subgroups according to ATB and administration method: CTZ bolus (CTZbolus), CTZ continuous infusion (CTZcontinuous), AMC bolus (AMCbolus), and AMC continuous infusion (AMCcontinuous). Once steady-state concentrations were reached, microdialysis was used to assess ATB levels in tissue adjacent to the ulcer. Serum and tissue samples were collected over a 6-h period. Bactericidal activity was assessed by peak concentrations (Cmax), area under the curve (AUC), and the proportion of time free drug concentrations remained above the minimum inhibitory concentration (fT > MIC). Target thresholds were fT > MIC ≥ 60% for CTZ and ≥ 50% for AMC. RESULTS:All patients achieved serum fT > MIC targets for CTZ and AMC in 100% of AMCbolus and 89% of AMCcontinuous. In tissue, target attainment was 60% (CTZbolus), 73% (CTZcontinuous), 79% (AMCbolus), and 83% (AMCcontinuous). Bolus administration led to rapid serum peaks (5 min) and delayed tissue peaks (30-60 min), with subsequent declines. Continuous infusion produced gradual concentration increases over time. CONCLUSIONS:While all patients achieved serum fT > MIC targets for CTZ and AMC (100% for AMCbolus and 89% for AMCcontinuous), target attainment in tissue was substantially lower. These findings suggest that although serum pharmacodynamic targets are reliably achieved, tissue exposure remains suboptimal.
AIMS:This study evaluated the impact of selected clinical factors on cognitive impairment (CI), particularly diabetic peripheral neuropathy (DPN) and impaired awareness of hypoglycaemia (IAH) in individuals with long-standing type 1 diabetes (T1D). MATERIALS AND METHODS:In this cross-sectional Hypoglycaemia Awareness Study in Diabetes Type 1 (HAD-1), 252 adults with T1D were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), with CI defined as a MoCA score < 26. IAH was identified using validated questionnaires (Clarke scale, Gold scale and Hypoglycaemia Awareness Questionnaire). RESULTS:The median MoCA score was 26 (23-28). CI was present in 122 subjects (48%), DPN in 85 subjects (34%) and IAH in 98 patients (39%). In univariate linear regression analysis, lower MoCA scores were associated with higher HbA1c (β = -0.30 and p = 0.017), older age (β = -0.03 and p = 0.014), a greater number of lifetime severe hypoglycaemia (SH) episodes (β = -0.17 and p = 0.001), DPN (β = -1.09 and p = 0.01) and higher skin autofluorescence (β = -0.72 and p = 0.03). In the multivariable regression analysis, IAH (β = -1.41 and p < 0.001), male sex (β = -0.89 and p = 0.022), higher HbA1c (β = -0.47 and p < 0.001) and higher vibration perception threshold (β = -0.049 and p = 0.004) were independent predictors of lower cognitive performance. Higher insulin dose (β = +2.92 and p = 0.012) was independently associated with better cognitive performance. In the interaction model, IAH (β = -1.54 and p = 0.003) and DPN (β = -1.18, p = 0.040) were independently associated with approximately 1.2-1.5-point lower MoCA scores. CONCLUSIONS:In individuals with T1D, DPN and IAH, a history of SH, poorer metabolic control, older age and male sex are associated with CI. People with T1D should be screened for CI, especially if they have DPN or IAH.
AIMS:Rural communities experience a higher prevalence of type 2 diabetes and diabetes-related mortality than urban populations. This study sought to disaggregate the influences of demographic and socioeconomic factors, food environment, diet quality, and dietary chemical exposures on diabetes risk in rural areas. MATERIALS AND METHODS:We enrolled participants from rural Sullivan County in an observational cohort study involving surveys and biospecimen collection measuring bisphenols and phthalates. We measured these endocrine disrupting chemicals found in food packaging, as rural residents generally consume canned foods and other shelf-stable foods more frequently than their urban counterparts. We used LASSO regression to compare the relative influence of these factors had on rural diabetes risk. RESULTS:Based on values for LASSO regression coefficients among 276 participants, the strongest risk factors for diagnosed diabetes included: older age (+0.486), lower household income (+0.172), Hispanic ethnicity (+0.124), red meat intake (+0.093), proportion of fast food restaurants among nearby restaurants (+0.071), and two phthalates (+0.149 and + 0.107). Among study participants without a history of diabetes, high HbA1c levels were associated with older age (+0.106), being non-Hispanic Black (+0.064), more trans-fat and red meat intake (+0.044 and +0.028), higher BMI (+0.014), higher levels of total bisphenols (+0.005), and higher levels of high-molecular weight phthalates (+0.002). CONCLUSIONS:Demographic and socioeconomic factors were the strongest predictors of rural diabetes risk; however, diet quality, food environment, and dietary chemical exposures also each played a key role. Our study identified modifiable risk factors, which could help reduce the burden of rural diabetes.
BACKGROUND:Social media has become a common source of educational information on type 2 diabetes. However, evidence regarding the quality of this content remains limited. This study evaluated the quality of short Spanish-language videos about type 2 diabetes published on Facebook, Instagram, TikTok, and YouTube. METHODS:A cross-sectional study analysed 400 short videos, including the top-ranked videos identified per platform (n = 100 each), collected between March 4 and 25, 2026. Spanish-language short-form videos (≤ 10 min) on type 2 diabetes intended for a general audience were included, while promotional or humourous content was excluded. Informational quality was assessed using the Journal of the American Medical Association (JAMA) benchmark criteria and the Global Quality Score (GQS). RESULTS:Overall, quality was low, with a mean GQS score of 2.5 ± 0.82 (on a 5-point scale) and low adherence to JAMA criteria, including authorship (35.5%), attribution (5.8%), and disclosure (1.0%). In multivariable analysis, videos on YouTube (β: 0.6; 95% CI: 0.3-0.8) and Instagram (β: 0.3; 95% CI: 0.1-0.5) had higher GQS scores compared with TikTok. Videos featuring a health professional were also associated with higher GQS scores (β: 0.4; 95% CI: 0.2-0.6). Compared with videos shorter than 30 s, videos lasting 31-60 s (β: 0.3; 95% CI: 0.0-0.6), 61-120 s (β: 0.5; 95% CI: 0.2-0.8), and more than 120 s (β: 0.7; 95% CI: 0.4-1.0) had higher GQS scores. CONCLUSION:Spanish-language type 2 diabetes-related videos on social media generally showed low quality. Higher quality was associated with content featuring healthcare professionals, longer video duration, and platforms such as YouTube and Instagram.
AIMS:To determine whether recovery of fasting C-peptide (ΔFCP) reduces deterioration in sudomotor small-fibre function, whether a threshold exists, and whether associations are complication-specific. METHODS:Retrospective real-world cohort of 288 hospitalised adults with diabetes with repeated fasting C-peptide and Sudoscan electrochemical skin conductance (ESC). Deterioration in sudomotor small-fibre function was defined as worsening foot ESC. Large-fibre neuropathy (LFN) and diabetic kidney disease (DKD) progression were assessed by nerve conduction and kidney outcomes. Cox models, restricted cubic splines, maximally selected rank statistics, and subgroup/landmark/sensitivity analyses were performed. RESULTS:Over a median 2.2 years, higher ΔFCP was independently associated with lower risk of deterioration in sudomotor small-fibre function, but not with LFN or DKD progression. Highest versus lowest ΔFCP tertile: adjusted HR 0.31 (95% CI 0.14-0.69; p < 0.001). An optimal ΔFCP cutoff of 126.8 pmol/L was identified; ΔFCP ≥ 126.8 pmol/L was associated with a 66% lower risk of sudomotor deterioration (HR 0.34, 95% CI 0.17-0.69; p < 0.001), remaining robust in landmark and sensitivity analyses. Baseline C-peptide mediated little of the association. CONCLUSIONS:Endogenous fasting C-peptide recovery is linked to a clinically meaningful, threshold-dependent reduction in the progression of sudomotor small-fibre dysfunction, supporting β-cell preservation/recovery as targets in early diabetic neuropathy.
BACKGROUND:The global rise of obesity has accelerated the onset of type-2 diabetes mellitus (T2DM) also among youth. Early detection of impaired β-cell function in at-risk populations is crucial for prevention; however, reference standards for children and adolescents remain scarce. We aimed to establish population-based percentile distributions specific to developmental stage and weight status for multiple markers of β-cell function in Chilean youth, thereby addressing this critical gap. METHODS:Cross-sectional study in 988 children and adolescents aged 6-17 years. Anthropometric measurements included weight, height, and waist circumference; weight status was classified using WHO 2007 standards. Participants were stratified into three developmental groups: Tanner 1-2 (G1), Tanner 3-5 (G2), and adolescents ≥ 16 years (G3). Fasting glucose and insulin were measured; insulin sensitivity and β-cell function were estimated using HOMA. Disposition index (DI) was calculated. RESULTS:G2 participants exhibited higher insulin, HOMA-IR, and HOMA-β levels, alongside lower HOMA-S levels compared to G1 and G3. Across all developmental groups, β-cell function varied by weight status: normal-weight individuals displayed more favourable insulin profiles than those with overweight or obesity. DI declined significantly with excess weight in G3, although values remained below 1.0 across groups. Fasting glucose was consistently within the normal range, independent of weight status. CONCLUSION:Our findings suggest that differences in β-cell function may be present even in the context of normal fasting glucose, indicating that glycaemia alone may not fully capture early variations in glucose-insulin dynamics. Since pubertal stage and adiposity significantly influenced these results, incorporating development- and weight-specific considerations may improve the interpretation of metabolic markers during growth. These findings support the need for more nuanced approaches to characterise metabolic variability in youth.
BACKGROUND:Type 1 diabetes mellitus has been associated with a significant risk of brain volume reduction and cognitive disorders, mainly affecting executive functioning and working memory. Therefore, an early impact of type 1 diabetes can be expected on volumetric measures and anatomic relationships among brain structures underlying these mental processes, as reflecting a process probably driven by developmental cognitive demands. With this aim, we compared volumetric measures and brain anatomical associations in young adults with type 1 diabetes and healthy controls. METHODS:Forty-one clinically well-controlled, right-handed type 1 diabetes patients aged 18-30 and with 10 or more years of disease evolution participated, along with forty-one healthy controls matched by age, sex, IQ, and years of schooling. They were all scanned with a 3-T MRI to obtain brain images with a voxel size of 1 mm3. The images were processed, and cortical gray and white matter were used to compute volumetric measures and cortical thickness, which were analyzed according to the corresponding segmentation map. Graph-theoretical analyses were also performed on adjacency resultant matrices. RESULTS:Global cortical volumes did not significantly differ between the groups. However, subcortical gray matter volume was significantly lower in the diabetes group (M = 43.4 cm3, SD = 3.3) compared with controls (M = 45 cm3, SD = 3.8; t(80) = -2.04, p = 0.045, d = 0.45). Patients also showed reduced volumes in cerebellar white matter, vermis, and brainstem, as well as decreased volumes in several frontal and subcortical regions, including the putamen and thalamus. These changes were found to correlate meaningfully with longer diabetes duration and age at disease onset. Graph-theoretical analyses further revealed alterations in brain network topology in the diabetes group. CONCLUSIONS:The results suggest that slight brain alterations affecting both brain microstructural integrity and typical organization early occur even in young patients with free-from-diabetes complications and clinically well-controlled type 1 diabetes. Moreover, these brain morphological changes appear to reflect the illness's distinctive impact on the developing brain, likely representing adaptive changes to address increasing cognitive and environmental demands.
BACKGROUND:The prevalence of diabetes has been increasing, particularly among younger age groups with prolonged survival, and the risk of complications and the burden of healthcare costs are also expected to rise. We investigated the concept of biological age (BA) in patients with diabetes and there by developed a model to predict the risk and time of onset of diabetes complications. METHODS:Using NHIS-NHID data, we analysed 686,410 patients with diabetes who had undergone a health examination in 2009-2010. We analysed patients' data until 2020. We developed a BA model for patients with diabetes and predicted the risk of complications and the time of complication onset. RESULTS:In both sexes, the incidences of all complications increased significantly with increasing corrected BA (p < 0.05). Similarly, the time until onset of all complications decreased significantly with increasing corrected BA (p < 0.05). CONCLUSIONS:Our study suggests that maintaining a lower BA is associated with a reduced risk of complications and a delayed onset of the disease, which may encourage diabetic patients to manage their health more effectively. This study is the first to apply the concept of BA, reflecting health and ageing status, to patients with diabetes to explore its relationship with the risk and timing of complications.
BACKGROUND:Type 1 diabetes (T1D) is a complex autoimmune disorder heavily influenced by heritable traits. However, the interplay between modifiable lifestyle factors and genetic susceptibility remains insufficiently characterised. This study sought to elucidate how genetic background and lifestyle determinants jointly affect T1D liability. METHODS:Utilising the UK Biobank cohort, we performed both cross-sectional and longitudinal assessments. A polygenic risk score (PRS) was computed to quantify genetic predisposition to T1D across 403,778 subjects. Concurrently, a composite lifestyle index was generated based on six domains: adiposity, smoking status, alcohol intake, physical exertion, diet quality, and sleep duration. We evaluated cross-sectional relationships using multivariable logistic regression and assessed longitudinal outcomes using Cox proportional hazard models. RESULTS:In a 15-year longitudinal study (median follow-up: 12.3 years) of 402,005 participants, 1474 cases of T1D were identified. Stratified by genetic risk, participants in the intermediate (hazard ratio [HR] = 1.17; 95% CI: 1.00-1.37) and highest (HR = 2.89; 95% CI: 2.46-3.39) risk groups demonstrated significantly elevated risks of incident T1D compared to the lowest risk group, independent of lifestyle factors. Conversely, when categorised by lifestyle patterns, both intermediate (HR = 0.61; 95% CI: 0.52-0.71) and healthy (HR = 0.43; 95% CI: 0.37-0.52) lifestyle groups exhibited substantially reduced risks of T1D compared to the unhealthy lifestyle group, irrespective of genetic predisposition. A significant interaction between genetic risk and lifestyle on the risk of T1D was found in both cross-sectional and longitudinal analyses (p < 0.001). CONCLUSIONS:The data reveal a robust inverse relationship between adherence to a healthy lifestyle and T1D incidence across all genetic strata, even among those with elevated hereditary risk. These results underscore the critical role of lifestyle modification in mitigating T1D susceptibility, distinct from genetic inheritance.
OBJECTIVE:To evaluate long-term weight trajectories and metabolic outcomes after bariatric surgery in patients with extreme obesity (BMI ≥ 60 kg/m2). BACKGROUND:Patients with BMI ≥ 60 kg/m2 represent a high-risk subgroup with a substantial cardiometabolic burden, yet long-term outcome data remain limited, particularly beyond 5 years and in cohorts including revisional surgery. METHODS:A retrospective cohort study included patients with BMI ≥ 60 kg/m2 who underwent bariatric surgery between April 2008 and August 2019. Outcomes included percentage total weight loss (%TWL), BMI change, and remission or improvement of metabolic comorbidities derived from structured medical records, with follow-up of up to 10 years. Early postoperative complications and mortality were also assessed. RESULTS:Sixty patients were included (mean age 41.5 years; mean baseline BMI 63.8 kg/m2; 67% female), 80% had obesity-related comorbidities and 23% underwent revisional surgery. Mean %TWL declined from 37.99% at ≤ 2 years to 37.36% at 2-5 years, 22.37% at 5-10 years, and 19.38% at > 10 years (p = 0.054). At the last follow-up (mean 72 months), mean BMI decreased to 45.11 kg/m2 and mean %TWL was 29.4%. Remission or improvement occurred in NAFLD (73.9%), type 2 diabetes (77.8%), obstructive sleep apnoea (85.7%), and hyperlipidaemia (70.0%), whereas hypertension improved in 29.1%. Two deaths occurred (3.33%): one perioperative death due to an anastomotic leak after revisional surgery and one late death unrelated to surgery. CONCLUSIONS:In BMI ≥ 60 kg/m2, bariatric surgery delivers durable metabolic benefits despite frequent long-term weight regain, supporting its role as a metabolic intervention beyond weight loss and underscoring the need for strategies that preserve metabolic health over time.
AIMS:To assess the global burden, trends, and inequalities of diabetes prevalence and treatment coverage among adults aged ≥ 45 years from 1990 to 2040. MATERIALS AND METHODS:Diabetes prevalence and treatment coverage data were obtained from the NCD-RisC database. Average annual percentage changes (AAPC) were estimated using join point regression, and a Bayesian age-period-cohort model was used to project diabetes prevalence and treatment coverage from 2023 to 2040. Cross-national health inequalities were measured using the slope index of inequality (SII) and the relative concentration index (RCI). RESULTS:Globally, diabetes prevalence rose from 12.85% in 1990 to 23.57% in 2022 (AAPC = 1.90%), and is projected to reach 37.44% by 2040 (AAPC = 2.59%). Treatment coverage grew from 33.22% to 45.88% (AAPC = 1.02%) and is projected to surge to 51.64% by 2040 (AAPC = 0.65%). Diabetes prevalence grew fastest in middle-income countries, whereas treatment coverage improved most in higher-income countries. The SII for prevalence burden decreased from -0.25% in 1990 to -14.86% in 2022, and is projected to further decline to -18.32% by 2040. For treatment coverage, the SII increased from 24.57% in 1990 to 43.91% in 2022, with a projected rise to 54.22% by 2040. The relative inequality measured by the RCI showed a similar pattern. CONCLUSION:Between 1990 and 2040, diabetes prevalence is projected to increase significantly, while treatment coverage shows only limited improvement. Over the same period, the diabetes prevalence burden is increasingly concentrated in resource-limited regions, while treatment accessibility is becoming progressively more concentrated in economically developed areas.
AIMS:This systematic review and meta-analysis evaluated the diagnostic performance of HbA1c, fasting plasma glucose (FPG), and 1-h plasma glucose (1hPG) against the 2-h plasma glucose standard (≥ 11.1 mmol/L) in adults without previously diagnosed diabetes. METHODS:A comprehensive search of Medline and CENTRAL (until 09.2025) identified population-based studies considering all available cutoff values for these markers. Diagnostic accuracy was estimated using bivariate random-effects models. Summary ROC curves and optimal cutoff values were derived using a Weibull accelerated failure time approach and the Youden index. Subgroup analyses explored potential differences across continents. The certainty of evidence (CoE) was evaluated using the GRADE approach. RESULTS:Fifty-eight studies including 276,203 participants were synthesised. Overall, FPG showed higher diagnostic accuracy than HbA1c, with an optimal cutoff of 6.3 mmol/L [95% confidence interval 6.0 mmol/L; 6.5 mmol/L], yielding 73% [68%; 78%] sensitivity and 91% [89%; 94%] specificity. The optimal HbA1c cutoff was 47 [42; 49] mmol/mol (i.e., 6.5% [6.0%; 6.6%]), with 62% [51%; 80%] sensitivity and 92% [77%; 96%] specificity. The CoE was low. Across all regions, FPG consistently outperformed HbA1c. Optimal FPG cutoff values ranged from 5.3 mmol/L in North America to 6.5 mmol/L in Asian countries, and from 41 mmol/mol (5.9%) in Asian countries to 45 mmol/mol (6.3%) in North America for HbA1c. CONCLUSIONS:These results suggest that FPG is a more reliable diagnostic marker than HbA1c and that uniform global thresholds may not fully reflect population-specific differences. Further high-quality studies are needed to refine diagnostic performance and examine factors influencing accuracy.
AIMS:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database. MATERIALS AND METHODS:This study analysed the U.S. FDA Adverse Event Reporting System (FAERS) data (Q2 2022-Q2 2025) for six GLP-1 Ras (exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide) to identify alopecia- and reproductive or endocrine-related a AEs. Disproportionality analyses were conducted using crude and adjusted reporting odds ratios (cROR and aROR) from logistic regression controlling for potential confounding factors. Sensitivity analyses with positive and negative controls were used to validate the signal robustness. RESULTS:A total of 1276 alopecia-related and 759 reproductive or endocrine-related cases were identified. Semaglutide showed significant positive associations with alopecia (aROR 1.23 [1.11-1.35]) and reproductive/hormonal disorders, including polycystic ovary syndrome (aROR 6.59 [3.73-11.64]) and menstrual abnormalities. In contrast, dulaglutide and tirzepatide demonstrated negative associations for several reproductive outcomes (e.g., dysmenorrhoea, amenorrhoea, heavy menstrual bleeding), indicating lower reporting odds in this dataset. Sensitivity analyses using control drugs confirmed the consistency and specificity of these findings. CONCLUSION:This real-world pharmacovigilance study identified agent-specific differences in the endocrine and dermatologic safety profiles of GLP-1 RAs. While semaglutide exhibited disproportionate reporting for alopecia and hormonal imbalance, dulaglutide and tirzepatide showed lower or non-significant disproportionality signals for these events. These results highlight the need for personalised agent selection and continued pharmacovigilance to optimise long-term patient safety.
AIMS:Gestational Diabetes Mellitus (GDM) is a common metabolic disorder that increases the risk of maternal obesity, type 2 diabetes, cardiovascular disease, and adverse neonatal outcomes. This study aimed to evaluate the associations of insulin use, physical activity, and perceived breast milk insufficiency with postpartum body composition in mothers with GDM. METHODS:A total of 190 mother-infant pairs (95 GDM, 95 healthy controls) from a tertiary care hospital were included. Maternal data were obtained by face-to-face interviews on postpartum day two, and perinatal data were retrieved from hospital records. Postpartum body composition was measured using a TANITA BC-730 bioelectrical impedance analyser. RESULTS:Mothers with GDM had higher postpartum obesity prevalence, body fat percentage, visceral fat, and estimated metabolic age, and lower total body water than controls (p < 0.05). Their infants were born at a shorter gestational age and were more frequently large for gestational age and macrocephalic (p = 0.002 and p = 0.029). Anthropometric indices did not differ between insulin-treated and untreated GDM mothers. Regular physical activity during pregnancy, particularly among controls, was associated with a more favourable postpartum body composition. Early breastfeeding initiation was less common and formula supplementation more frequent in GDM mothers (p = 0.018 and p = 0.01). Perceived milk insufficiency was not linked to anthropometry. CONCLUSIONS:Mothers with GDM exhibited adverse postpartum body composition and less favourable early breastfeeding behaviours, whereas prenatal physical activity was associated with more favourable indices.
