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Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD+ precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. This 12-week, outpatient, phase 2, single-site (Children's Hospital of Philadelphia, Philadelphia, PA, USA), randomised, 2 × 2 factorial clinical trial recruited individuals aged 10-40 years with an ejection fraction of 45% or greater who were able to exercise. A computer-generated randomisation sequence was developed by the trial statistician. Random allocation was age-stratified (<18 years vs ≥18 years) to one of four groups: placebo and no exercise with attention control (weekly phone calls; henceforth placebo only), nicotinamide riboside and no exercise with attention control (henceforth nicotinamide riboside only), placebo and exercise (exercise only), and nicotinamide riboside and exercise (combination therapy). Individualised exercise plans were developed by the exercise physiologist (three aerobic and two resistance training sessions weekly), performed at the individual's home, and overseen remotely (telephone check-ins by the physiologist). Weight-based dosing of nicotinamide riboside or placebo was 300 mg (1 capsule) for weights of 24 kg up to 48 kg, 600 mg (2 capsules) for weight 48 kg up to 72 kg, and 900 mg (3 capsules) for weights of over 72 kg. The primary outcome was change in peak VO2 (L/min) during cardiopulmonary exercise testing at 12 weeks versus baseline, and the effect of treatment group was assessed in a statistical model accounting for age (stratification variable), sex, and baseline peak VO2. Stage 1 analysis tested the difference between each active treatment versus the control group, and stage 2 analysis (if combination therapy was effective) tested the difference between combination treatment and exercise alone; family-wise type 1 error was maintained <0·05. Analyses were by intention-to-treat. Adverse events were recorded systematically. This trial is registered with ClinicalTrials.gov (NCT04192136) and is complete. Between Sept 3, 2020, and April 23, 2025, we enrolled 74 individuals, of whom 66 met the eligibility criteria and were randomly allocated to the four study groups. All participants completed the study. 33 (50%) were children (aged 10-17 years) and 33 (50%) were adults (aged ≥18 years); 37 (56%) were male and 29 (44%) were female. Least mean squares for the change in peak VO2 in L/min were -0·05 (95% CI -0·16 to 0·06) for the 17 participants in the control group; 0·06 (-0·05 to 0·17) for the 17 participants in the nicotinamide riboside and no exercise group; 0·11 (0·00 to 0·22) for the 16 participants in the placebo and exercise group; and 0·16 (0·05 to 0·27) for the 16 participants in the nicotinamide riboside and exercise group. Differences between active treatment and the control group were 0·10 (95% CI -0·05 to 0·26; padjusted=0·188) for nicotinamide riboside and no exercise; 0·16 (0·00 to 0·31; padjusted=0·103) for placebo and exercise; and 0·21 (0·05 to 0·36; padjusted=0·0299) for nicotinamide riboside and exercise in combination. Combination therapy was not statistically different from exercise alone (difference -0·05 ([95% CI -0·10 to 0·21]; p=0·49). Adverse events were all mild or moderate, and included gastrointestinal symptoms, falls, upper respiratory infections, and skin rashes. At least one moderate adverse event of interest in these categories was reported by seven (41%) participants in the control group; six (35%) in the nicotinamide riboside and no exercise group; three (19%) in the placebo and exercise group; and four (25%) in the nicotinamide plus exercise group. The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich's ataxia. Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach. US National Institutes of Health and Friedreich's Ataxia Research Alliance.
Although VAI, LAP, TyG and TyHGB are considered alternative indicators of abdominal fat deposition, their longitudinal association and strength of these indices with T2D remain unclear. The study aimed to evaluate the association between the indices and onset T2D in the elderly population across different FBG statuses and compare their predictive performance in risk assessment. Data were from the BaHLS, a cohort study of community-dwelling elderly individuals in Shenzhen, China. The study examined the associations between six novel obesity- and lipid-related indices (including BMI, WC, VAI, LAP, TyG and TyHGB) and the onset of T2D across different FBG statuses, including normal and elevated FBG. A multivariate Cox proportional hazards model and a GAM were employed to assess the longitudinal associations between each index and T2D. ROC curves analysis and AUC were utilized to evaluate the predictive performance of indices and determine their optimal cutoff values. A total of 18,251 participants were enrolled in the study, with 1,350 (7.40%) participants were diagnosed with T2D by end of 2022. In the overall elderly cohort, the adjusted HRs of T2D per one-standard-deviation increase were: BMI 1.17 (95% CI: 1.11-1.23), WC 1.23 (95% CI: 1.16-1.30), VAI 1.30 (95% CI: 1.24-1.37), LAP 1.21 (1.17-1.26), TyG 1.76 (95% CI: 1.67-1.86), and TyHGB 1.37 (95% CI: 1.33-1.42). Except for BMI and WC, the remaining indices were independent risk factors for the onset of T2D in both normal and elevated FBG individuals. These indices showed significant associations with T2D across different subgroups. Regarding predictive performance, all six indices demonstrated predictive ability for the onset of T2D across all participants (AUC > 0.5, P< 0.001). Specifically, TyG (AUC = 0.706, 95% CI: 0.691-0.721) and TyHGB (AUC = 0.737, 95% CI: 0.724-0.750) exhibited better predictive performance than the other indices. RCS analysis revealed that BMI and WC exhibited linear associations with the risk of T2D across all participants, whereas VAI, LAP, TyG, and TyHGB demonstrated nonlinear relationships. The study demonstrated that 6 obesity- and lipid- indices are positively associated with the incidence of onset T2D, and TyG and TyHGB demonstrated superior predictive performance for the onset of T2D in the elderly. Suggesting that TyG and TyHGB should be served as a valuable indicator for monitoring and preventing T2D.
Overweight and obesity are increasingly common in adults with type 1 diabetes (T1D), contributing to insulin resistance, higher insulin requirements, and greater cardiometabolic burden. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown major metabolic benefits in type 2 diabetes and obesity, but its role in T1D remains unclear. This systematic review evaluated tirzepatide as adjunctive therapy to insulin in adults with T1D and overweight or obesity. This review followed PRISMA 2020 and was registered in PROSPERO (CRD420261335230). PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies included randomized and observational studies reporting efficacy or safety outcomes of tirzepatide added to insulin in adults with T1D. Because of marked clinical and methodological heterogeneity, findings were synthesized qualitatively without meta-analysis, and certainty of evidence was assessed using a GRADE-based framework. Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias. The most consistent finding was body weight reduction. In the randomized trial, tirzepatide reduced mean body weight by 10.3 kg, with an estimated treatment difference of 8.7 kg versus placebo, corresponding to an 8.8% reduction from baseline. A placebo-adjusted 35.1% reduction in total daily insulin dose and a between-group HbA1c difference of -0.4 percentage points were also reported, although glycaemic findings were short-term and imprecise. Gastrointestinal adverse events were the most frequent safety findings. Evidence certainty was low or very low. Tirzepatide may be a promising investigational adjunct in selected adults with T1D and overweight or obesity, particularly for weight reduction. However, current evidence remains insufficient to establish durable glycaemic benefit or long-term safety. Larger randomized trials are needed.
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major microvascular complications of type 2 diabetes mellitus (T2DM), sharing common inflammatory and metabolic pathways. Chemerin, an adipokine involved in inflammation and endothelial dysfunction, may serve as an early biomarker for DN. To evaluate serum Chemerin levels in type 2 diabetic patients across different stages of albuminuria and to explore its correlation with anthropometric indices and inflammatory markers. This case-control study included patients with T2DM categorized according to urinary albumin excretion into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. Serum Chemerin levels were measured using ELISA. All participants underwent comprehensive fundus examination after pupillary dilation, and diabetic retinopathy was graded according to standard clinical criteria. Clinical, biochemical, and metabolic parameters were recorded and correlated with albuminuria stages and retinal findings. Serum Chemerin levels were significantly elevated in diabetic patients with micro- and macro-albuminuria compared with normo-albuminuric patients and healthy controls. Median Chemerin levels increased progressively from 721 ng/mL in the normo-albuminuric group to 1367 ng/mL in the micro-albuminuria group and 2793 ng/mL in the macro-albuminuria group (p < 0.001). Similarly, inflammatory markers demonstrated a stepwise increase with worsening albuminuria; median IL-6 levels rose from 6.34 pg/mL in normo-albuminuric patients to 7.34 pg/mL and 9.6 pg/mL in the micro- and macro-albuminuria groups, respectively, while TNF-α increased from 94 pg/mL to 124 pg/mL and 296 pg/mL across the same groups (p < 0.001). Insulin resistance indices also increased significantly, with median HOMA-IR values rising from 2.45 in normo-albuminuric patients to 3.29 and 4.68 in the micro- and macro-albuminuria groups (p < 0.001). Serum Chemerin showed strong positive correlations with albuminuria (r = 0.85), HOMA-IR (r = 0.85), IL-6 (r = 0.873), and TNF-α (r = 0.813), while demonstrating negative correlations with eGFR and serum albumin. Additionally, the prevalence of diabetic retinopathy increased significantly across albuminuria stages, reaching 82.6% in the macro-albuminuria group (p = 0.001). Serum Chemerin is significantly elevated in T2DM patients with albuminuria and correlates with both inflammatory markers and retinal microvascular changes, suggesting its potential utility as an adjunct biomarker for diabetic nephropathy and systemic microvascular complications. Fundus examination findings reinforce the parallel progression of diabetic nephropathy and retinopathy, highlighting shared pathogenic mechanisms.
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterised by progressive destruction of pancreatic β-cells, in which inflammatory cytokines such as interleukin-6 (IL-6) and oncostatin M (OSM) play key roles. This study aimed to evaluate serum IL-6 and OSM levels and their relationship with glycemic indices in children with T1DM. In this cross-sectional study, 80 children (40 with T1DM and 40 controls) aged 3-18 years were included. Exclusion criteria were congenital or inflammatory disorders and use of anti-inflammatory drugs, corticosteroids, NSAIDs, antibiotics, lipid-lowering agents, hypoglycemic drugs, herbal supplements, multivitamins, or special diets. Serum IL-6, OSM, fasting blood sugar (FBS), and HbA1c were measured. Demographic and clinical data-including age, sex, growth percentiles, BMI percentile, blood pressure, duration of diabetes, and history of diabetic ketoacidosis (DKA)-were recorded. Logistic regression was used to identify predictors of glycemic indices, and ROC curve analysis assessed the diagnostic performance of OSM. Statistical significance was set at p < 0.05. Out of 80 subjects, the mean age was 10.62 (3.3) years in children with T1DM and 11.25 (3.6) years in controls, with a comparable gender distribution (male: 52.5% vs. 60%). Serum OSM levels were significantly higher in children with T1DM (p < 0.001) and strongly predicted elevated HbA1c (adjusted OR = 3.06; 95% CI: 1.84-5.08) and FBS (adjusted OR = 1.70; 95% CI: 1.31-2.20). ROC analysis demonstrated a robust ability to discriminate T1DM from controls (AUC = 0.94; 95% CI: 0.89-0.99), with a cut-off of OSM > 10.0675, yielding a sensitivity and specificity of 87.5%. IL-6 levels did not differ significantly between groups but were higher in children with a history of DKA. OSM may represent a sensitive and specific biomarker for distinguishing children with T1DM from healthy individuals, whereas IL-6 appears more closely related to DKA-associated inflammation.
Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM), and its early identification is crucial. As a novel endocrine marker, the relationship between sclerostin and DKD, as well as its combined diagnostic value with 25-hydroxyvitamin D (25(OH)VD), remains unclear. This study aims to investigate circulating sclerostin levels in patients with DKD and its combined diagnostic value with 25(OH)VD, providing evidence for early clinical diagnosis. A total of 308 patients with T2DM were enrolled, including 113 with DKD (DKD group) and 195 without DKD (T2DM group). The DKD group was subdivided into microalbuminuria and macroalbuminuria groups based on UACR. General information and clinical indicators were collected for all patients. Concurrently, blood samples were collected to measure serum sclerostin levels using the ELISA method. Statistical analysis evaluated sclerostin expression differences across groups and its correlations with other indicators. Binary logistic regression analyzed the independent associations of sclerostin and 25(OH)VD with DKD. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of serum sclerostin and 25(OH)VD levels for T2DM with albuminuria. Compared to the T2DM group, patients in the DKD group exhibited decreased serum sclerostin and 25(OH)VD levels (P< 0.05). Further subgroup analysis of DKD revealed that serum sclerostin levels were significantly lower in both the microalbuminuria and macroalbuminuria groups compared to the normal albuminuria group (P< 0.05). Serum 25(OH)VD in the massive proteinuria group was significantly lower than in both the normal proteinuria and microalbuminuria groups (P< 0.05). Correlation analysis showed a significant negative correlation between sclerostin and UACR (r = -0.197, P< 0.001) and a significant positive correlation with 25(OH)VD (r = 0.167, P = 0.003). Binary logistic regression analysis demonstrated that serum sclerostin and 25(OH)VD remained independent predictors of DKD even after adjusting for variables. ROC curve analysis showed that the AUC for predicting DKD using serum sclerostin and 25(OH)VD was 0.73, with a sensitivity of 61.1% and specificity of 75%. This study confirms that serum levels of sclerostin and 25(OH)VD are significantly reduced in patients with DKD, and both are independent protective factors for DKD. Their combined assessment demonstrates good predictive value for the early identification of DKD, providing clinical insights into the interaction between bone metabolism and renal pathology.
Background and objectives Insulin resistance and elevated endothelin-1 (ET-1) levels are key contributors to cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and hypertension. This study compared the effects of telmisartan with other commonly used antihypertensive agents on insulin sensitivity in terms of homeostatic model assessment for insulin resistance (HOMA-IR) and vascular endothelial function in terms of ET-1 levels in patients with T2DM and hypertension. Methods In this randomised, open-label study, 182 patients with coexisting T2DM and hypertension were screened between May 2023 and September 2024. The study was registered with the Clinical Trials Registry-India (CTRI; CTRI/2023/04/051878). Seventy eligible patients were enrolled and randomised 1:1 to receive telmisartan (n=34) or other antihypertensive agents (amlodipine, n=22; cilnidipine, n=12; ramipril, n=2; total n=36) for 12 weeks. The primary outcome was the change in insulin sensitivity as measured by the HOMA-IR. ET-1 levels were evaluated as a secondary outcome. Results At baseline, the median HOMA-IR values were 4.1 [interquartile range (IQR): 2.2-5.9] in the telmisartan group and 3.9 (IQR: 3.1-5.9) in the comparator group. After 12 weeks, the median HOMA-IR significantly decreased in the telmisartan group to 1.79 (IQR: 1.30-2.63) compared to 3.45 (IQR: 2.43-5.12) in the other antihypertensive group (P=0.001). Baseline ET-1 levels were 19.23 pg/mL (IQR: 10.8-29.9) and 17.1 pg/mL (IQR: 10.3-26.48) in the telmisartan and comparator groups, respectively. At 12 weeks, median ET-1 levels decreased to 12.49 pg/mL (IQR: 5.70-18.70) and 11.22 pg/mL (IQR:4.84-23.20), respectively (P=0.90). Interpretation and conclusions Telmisartan significantly improved insulin sensitivity at 12 weeks compared to other antihypertensive agents in patients with T2DM and hypertension. However, the reduction in ET-1 levels was similar across groups, suggesting a comparable effect on endothelial function over 12 weeks. These findings suggest that, beyond its antihypertensive action, telmisartan may offer favourable metabolic benefits that could help limit diabetes-related micro- and macrovascular complications compared with other commonly prescribed antihypertensives.
This systematic review aims to investigate if macronutrient ordering is effective at lowering postprandial glucose excursions in individuals with diabetes. A systematic search of Medline, Embase and Web of Science was conducted up to February 2025. Two independent reviewers screened title and abstract using Covidence software. Data extraction and risk of bias assessment were performed by one reviewer and checked by a second reviewer. Findings were synthesized narratively. PROSPERO registration: CRD42025639742. In total, we included six studies involving 144 participants. Most studies reported that a carbohydrate last meal pattern was effective at lowering postprandial glucose excursions in individuals with diabetes. There was some evidence for the carbohydrate last meal pattern lowering insulin levels and increasing GLP-1 and GIP levels in individuals with diabetes. The risk of bias ranged from low to some concerns, and the GRADE assessment showed a low certainty of evidence. Evidence suggests that the carbohydrate last meal pattern effectively reduces postprandial glucose excursions in individuals with diabetes. However, significant heterogeneity in study design limits overall certainty in the findings. Further research is needed to confirm these effects.
Type 2 diabetes mellitus (T2DM) affects over 500 million people worldwide, with traditional therapies often failing to maintain long-term glycaemic control. Ecnoglutide, a novel long-acting GLP-1 receptor agonist, has emerged as a promising therapeutic option. This systematic review and meta-analysis evaluated the efficacy and safety of ecnoglutide in adults with T2DM. Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, ScienceDirect, ClinicalTrials.gov, and Google Scholar through September 2025. Randomized controlled trials comparing ecnoglutide with placebo or active comparators in adults with T2DM were included. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included fasting plasma glucose, insulin resistance markers, lipid profile, liver enzymes, and adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analysis was performed using random-effects models, with mean differences and risk ratios calculated at 95% confidence intervals. Four RCTs comprising 1643 participants (1162 receiving ecnoglutide, 444 controls) were included. Ecnoglutide significantly reduced HbA1c (MD = -0.44, 95% CI -0.55 to -0.33, p < 0.00001), body weight (MD = -5.63, 95% CI -7.90 to -3.35, p < 0.01), and fasting plasma glucose (MD = -0.81, 95% CI -1.03 to -0.59, p < 0.00001). Improvements were observed in insulin sensitivity, lipid profile, and liver enzymes. Adverse events occurred more frequently with ecnoglutide (RR = 1.09, p < 0.01), although predominantly gastrointestinal and mild-to-moderate, with no significant differences in serious adverse events. Ecnoglutide demonstrates robust efficacy in glycaemic control, weight reduction, and cardiometabolic parameters with an acceptable safety profile in adults with T2DM, supporting its therapeutic potential as a next-generation GLP-1 receptor agonist.
We conducted the diet and diabetes remission (DIREM) study to assess whether an integrated lifestyle intervention would lead to achieving remission in type 2 diabetes. Patients with type 2 diabetes were randomly assigned to calorie-carbohydrate restriction (CCR) group, intermittent fasting with calorie-carbohydrate restriction (IFCCR), or usual care group (control). The total study duration was 6 months, consisting of two phases: a 12-week integrated lifestyle intervention (ILI) phase, followed by a 12-week maintenance and structured monitoring (MSM) phase. The intervention was presented in the form of a structured behavioural model and also emphasised physical activity. One hundred and twenty participants were randomly assigned to the study. Diabetes remission occurred in 9 (22.5%) of 40 participants in the CCR group (OR (CCR vs. Control) = 11.7, 95% CI: 1.4-98.3; p = 0.024), 12 (30.0%) of 40 participants in the IFCCR group (OR (IFCCR vs. Control) = 18.1, 95% CI: 2.2-151.0; p = 0.007) and 1 (2.5%) of 40 participants in the control group. The odds of remission were higher in the IFCCR group compared to the CCR group, but it was not significant (OR (IFCCR vs. CCR) = 1.5, 95% CI: 0.6-4.3; p = 0.4). Both calorie-carbohydrate restriction alone and in combination with intermittent fasting significantly improved glycemic control and induced diabetes remission compared with the control group. No significant difference was found between the two interventions. Larger long-term studies are needed to confirm these findings. This trial was registered in the Iranian Registry of Clinical Trials (IRCT), IRCT20240418061519N1 (https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20240418061519N1).
The growing number of hypoglycaemia risk prediction models for Type 2 diabetes mellitus (T2DM) underscores the need for systematic evaluation of their risk of bias and applicability. This study summarises and critically assesses their characteristics and predictive performance using established guidelines for prediction model development. The review protocol was registered on PROSPERO (CRD420251031980). We searched nine main English and Chinese databases from inception to May 2025. The CHARMS checklist and PROBAST tool were used to assess the risk of bias and applicability. A meta-analysis of AUC values from models was conducted using MedCalc software. We included 25 studies (45 models), with reported AUCs ranging from 0.630 to 0.996. The pooled AUC value of 16 models was 0.815 (95% CI 0.765-0.861), indicating excellent discrimination. 24 (96%) studies were overall at high risk of bias and 22 (88%) studies had low-risk applicability, primarily due to small sample size, improper handling of missing data, failure to report calibration, screening of predictors by univariate analysis and lack of external validation. Current hypoglycaemia prediction models for T2DM show substantial methodological limitations and high bias risk. While machine learning models have advanced rapidly in recent years, their methodology remains opaque and validation is limited. Future research should focus on optimising existing models, enhancing methodological rigour and conducting external validation.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used to manage diabetes and are known to cause weight loss. This study aimed to clarify whether SGLT2i-induced weight loss influences survival or toxicity during systemic therapy in patients with advanced non-small cell lung cancer (NSCLC) and comorbid diabetes. We conducted a retrospective analysis of patients with advanced NSCLC and diabetes who received first-line systemic therapy. Patients with an Eastern Cooperative Oncology Group performance status (PS) ≥ 3, driver mutations, interstitial lung disease, untreated diabetes, or missing data were excluded. We compared weight changes, progression-free survival (PFS), overall survival (OS), and adverse events between patients with and without SGLT2i. We defined cachexia as either 5% or more body-weight loss within six months prior to the initiation of lung cancer treatment or weight loss greater than 2% and a body-mass index (BMI) of less than 20 kg/m2. Eighteen patients (21.9%) out of 82 received SGLT2i for diabetes. There was no difference in the incidence of cachexia between the two groups (66.7% vs. 46.9%, p = 0.184), despite significant weight loss in the SGLT2 group compared to the non-SGLT2 group (median - 5.8% vs. - 3.4%, p = 0.039). No significant differences were observed in progression-free survival (PFS) (median 6.2 vs. 4.1 months, p = 0.512) or overall survival (OS) (median 11.9 vs. 14.6 months, p = 0.583). Grade ≥ 3 adverse events occurred in 11.1% of patients in the SGLT2i group and 31.2% of patients in the non-SGLT2i group (P = 0.132). There were no cases of diabetic ketoacidosis or urinary tract infections. SGLT2 inhibitors were associated with weight loss and were not associated with worse survival or increased toxicity in this limited retrospective cohort.
Obesity management in the UK includes multicomponent weight and behavioural interventions delivered at Tier 3 of the NHS model of care. This study presents the impact of and comparative outcomes for the Tier 3 Southeast London Healthy Living programme (SELHLP) in a diverse population. The SELHLP is a multicomponent, multidisciplinary programme that includes face-to-face (F2F) and virtual (V) delivery. Two management strategies are offered: Balance, a weight behavioural intervention and Kickstart, a three-month total meal replacement intervention followed by a weight and behavioural intervention. Eligibility criteria were adults (≥ 18 years) with a BMI ≥ 35 kg/m2. Baseline data and exit data were collected at session 9-12. Primary outcomes included weight change from baseline to programme completion; secondary outcomes included both clinical and behavioural outcomes. Programme completers of both Balance and Kickstart were predominantly female (82% and 79% respectively). Among completers for Balance, weight change from baseline was -2.8 (8.4) kg for Balance F2F (p < 0.001) and -5.1 (11.7) kg for Balance V (p < 0.001). A similar trend was observed for Kickstart F2F -11 (13) kg and Kickstart V -11 (11) kg (p < 0.001) but did not differ between service delivery models (p > 0.005). 34% of participants of the combined Balance and Kickstart programmes lost ≥ 5% of initial weight, -10.7% and -18% weight loss respectively. Black participants and women were less likely to achieve ≥ 5% weight loss in both programmes, but deprivation status had no effect. The SELHLP resulted in significant weight loss, but weight loss varied by service delivery, ethnicity and sex. Future efforts should focus on cultural salience and digitisation of Tier 3 programmes to support better engagement and completion among participants of Black ethnicity. Tailoring of Tier 3 interventions and triaging of participants at the onset should be investigated to improve both patient and service outcomes.
Preterm birth increases the long-term risk of diabetes and chronic kidney disease (CKD), yet its impact on diabetic kidney disease (DKD) is unclear. We previously showed that male preterm mice with diabetes develop early features of DKD, including reduced podocyte density, decreased renin expression, activation of angiogenesis pathways, and impaired endothelial-podocyte signaling. Here, we examine whether preterm birth similarly accelerates DKD progression in female mice and compare structural and transcriptomic outcomes in the females to the prior male cohort to assess sex-specific differences. Preterm mice were delivered by Caesarean section at 19 days post conception (dpc) and term mice at 20 dpc. Hyperglycemia was induced at 6 weeks with streptozotocin to generate term-diabetic (T-D) and preterm-diabetic (PT-D) groups; controls were term-nondiabetic (T-ND) and preterm-nondiabetic (PT-ND). Body weight and glucose were monitored, and kidneys were analyzed at 18 weeks using histologic, stereologic, imaging, and transcriptomic methods. Compared with T-ND females, PT-D females showed higher albuminuria, more atubular glomeruli, reduced proximal tubule (PT) fraction, and pro-fibrotic gene activation. Compared to T-D females, PT-D females had higher blood urea nitrogen (BUN) levels and reduced PT fraction. This was associated with activation of pathways associated with the vasculature and suppression of mitochondrial metabolism gene pathways, along with Notch signalling alterations. Sex differences included a lower PT fraction in preterm females than males and fewer atubular glomeruli in PT-D females than PT-D males. Renin expression was lower in PT-D than T-D in males only. When comparing PT-D to T-D across sexes, 582 differentially expressed genes were unique to females. Notch signalling was upregulated in both male and female PT-D mice compared to T-D. Preterm birth increases susceptibility to kidney injury in females after exposure to hyperglycemia. However, preterm females with hyperglycemia are more resistant to kidney damage than males.
Type 2 diabetes mellitus (T2DM) is a growing public health concern among older adults worldwide including in Iran. Despite extensive research on the metabolic effects of dairy products, their association with T2DM remains inconsistent, particularly in non-Western populations. This study examined the relationship between dairy consumption including specific types, and T2DM among older adults in eastern Iran. This cross-sectional study utilised baseline data from the Birjand Longitudinal Aging Study (BLAS), which included community-dwelling adults aged 60 years and older. Dietary intake was assessed using structured questionnaires, and participants were categorised into tertiles based on dairy consumption (low, moderate, high). T2DM status was determined by FBS ≥ 126 mg/dL or a previous physician diagnosis. Logistic regression models estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM across different levels of dairy intake, adjusting for potential confounders. Data from 1348 participants were analysed, with an overall T2DM prevalence of 27.15%. Individuals in the highest tertiles of yogurt and cheese intake had significantly increased odds of T2DM (OR = 1.454, 95% CI = 1.08-2.20, p = 0.08; OR = 1.44, 95% CI = 1.04-2.00, p = 0.029). No significant association was found between milk consumption and T2DM risk. Total dairy consumption showed no significant association with T2DM in the fully adjusted model (OR = 1.42, 95% CI = 1.00-2.403, p = 0.05). This study reveals a complex association between dairy intake and the risk of T2DM in Iran, in which high consumption of yogurt and cheese was paradoxically associated with increased odds of disease. This finding may be explained by the high fat content of these products, residual confounding from unmeasured dietary patterns, or biological pathways related to diabetes pathology and gut microbiota modulation that were not captured in our analysis.
Gestational diabetes mellitus (GDM) may increase the risk of maternal chronic kidney disease (CKD). The association of GDM with maternal CKD has been heterogeneous across studies, and this association remains controversial. The aim of this systematic review was to investigate the association of GDM with the risk of maternal CKD. MEDLINE/PubMed, EMBASE, Scopus and Web of Science were searched, with no time limit, up to 25 August 2025 by two independent investigators to identify studies that had assessed the association of GDM with maternal risk of CKD. Heterogeneity between studies was assessed using Cochrane's Q and I2 tests. Meta-regression was performed to identify factors associated with heterogeneity. Eleven cohort studies involving 21,313,434 participants (1,530,599 (7.2%) GDM) were included. Pooled estimates from eleven studies showed that GDM was significantly associated with an increased risk of maternal CKD (HR: 2.19; 95% CI: 1.7, 2.68; p: 0.001, I2:92.2%). Further analyses restricted to studies adjusting for key confounders (HR: 2.47; 95% CI: 1.87, 3.08; p: 0.001, I2:24.2%) also showed a significant association. While pooled estimates from three studies did not show a significant association between GDM and an increased risk of AKI (HR: 1.1; 95% CI: 0.94, 1.26). Subgroup analyses showed that GDM was significantly associated with an increased risk of maternal CKD in both DM + (HR: 6.24) and DM - (HR: 1.4). Gestational diabetes mellitus (GDM) with and without DM was significantly associated with an increased risk of maternal CKD. GDM with DM had a synergistic effect on maternal CKD risk. Although GDM was not significantly associated with increased AKI, only three studies were included in the AKI analysis, which may have affected these results by random error and therefore lack sufficient power and evidence to draw conclusions.
Diabetic neuropathy (DN) is the most common chronic complication of Type 2 diabetes mellitus (T2DM), with reported prevalence ranging from 23% to 54.5%. This study evaluated the prevalence, clinical characteristics, and treatments of DN using Korean National Health Insurance Service (NHIS) data from 2012 to 2017. We analyzed NHIS sample data for 8.7 million individuals stratified by age, sex, eligibility, and income. DN was defined using ICD-10 codes (E10.4-E14.4, G59.0, G63.2, G99.0) and concurrent prescriptions for diabetes and DN. Annual DN prevalence among diabetes patients was calculated, and treatment patterns and patient characteristics were compared between those with and without DN. DN prevalence declined from 23.4% in 2012 to 21.5% in 2017. About half of DN patients received pharmacologic treatment-mainly monotherapy (up to 82%), followed by dual (15%) and triple therapy (3%). The most prescribed drugs were α-lipoic acid (52.1%-55.0%), anticonvulsants (30.4%-34.5%), tricyclic antidepressants, SNRIs, and γ-linolenic acid. DN patients were generally older, more often female, and had more comorbidities such as hypertension, dyslipidemia, cardiovascular disease, diabetic foot, and amputations. They were also more likely to use insulin or multiple oral agents. About one-quarter of patients with T2DM had DN, and half received treatment, mostly α-lipoic acid monotherapy. DN patients tended to be older and had multiple comorbidities, resulting in higher hospitalization rates.
Background/Objectives: Liver fat represents an early metabolic lesion in the development of diabetes and its cardiometabolic complications. Diets high in free sugars, particularly from sugar-sweetened beverages (SSBs), are associated with abdominal obesity and increased cardiometabolic risk, prompting global guidelines to limit SSBs as a major public health strategy. Low-fat cow's milk is promoted as the preferred caloric replacement strategy for SSBs due to its high nutritional value and cardiometabolic advantages. Fortified soymilk is a plant-based alternative with approved health claims for cholesterol and coronary heart disease risk reduction that offers an equivalent nutritional value to cow's milk. However, given concerns about its classification as an ultra-processed food (UPF), it is unclear whether soymilk offers comparable metabolic health benefits to milk as part of clinical and public health strategies to reduce SSB intake. The Soy Treatment Evaluation for Metabolic (STEM) health trial seeks to evaluate the impact of replacing SSBs with either 2% soymilk or 2% cow's milk on liver fat and other cardiometabolic risk factors in habitual adult consumers of SSBs with obesity. Methods: The STEM trial is a 24-week, pragmatic, 3-arm, parallel, randomized trial. We recruited adults with obesity (high BMI plus high waist circumference based on ethnic specific cut-offs) consuming ≥1 SSB/day. Participants were randomized to one of three groups based on their usual SSB intake at baseline (servings/day): continued SSB (355 mL can) intake; replacement with fortified, sweetened 2% soymilk (250 mL); or replacement with 2% cow's milk (250 mL). The primary outcome is the change in intrahepatocellular lipid (IHCL) measured by 1H-MRS at 24 weeks. Hierarchical testing will be done to reduce the familywise error rate. The superiority of cow's milk to SSBs will be assessed first to establish assay sensitivity. If superiority is established, then the non-inferiority of soymilk to cow's milk will be assessed using a pre-specified non-inferiority margin of 1.5% IHCL units (assessed by difference of means using a 90% confidence interval [CI]). Analyses will be conducted according to the intention-to-treat (ITT) principle using inverse probability weighting (IPW) for superiority testing and per-protocol analyses for non-inferiority testing, using ANCOVA adjusted for age, sex, metabolic dysfunction-associated steatotic liver disease (MASLD) status, medication use, intervention dose, and baseline levels. We hypothesize that soymilk will be non-inferior to cow's milk (Clinicaltrials.gov NCT05191160). Results: Recruitment began in November 2021. A total of 3050 individuals were screened. We randomized 186 participants (62 per group) between 19 April 2022 and 16 April 2024. Participants are 57% male; with a mean [SD] age of 39.9 [11.8] years; BMI of 34.6 [6.1] kg/m2, waist circumference of 112.6 [13.8] cm; IHCL of 10.0 [8.2] % with 64.1% meeting the criteria for MASLD; and SSBs intake of 2.3 [1.3] servings/day. Conclusions: Baseline characteristics were balanced across the study arms, with participants representing adults with a high-risk metabolic phenotype, and 64.1% meeting the criteria for MASLD. Findings will contribute to evidence on the cardiometabolic benefits of soymilk, informing clinical practice guidelines and public health policy.
Optimal inpatient diabetes management requires accurate blood glucose (BG) and ketone (BK) documentation. In 2019, Royal Melbourne Hospital implemented hospital-wide networked blood glucose monitoring (NBGM) (NovaBiomed StatStrip), which automatically uploads BG/BK values to point-of-care device software (Bioconnect). Until electronic health record (EHR) implementation in 2020, nurses manually recorded BG/BK data into paper-records, enabling blinded gold-standard accuracy assessment by digital software. This study evaluated the accuracy and potential clinical significance of inaccurate manual POC BG/BK values compared with NBGM records. DINGO POC, a sub-analysis of the Diabetes IN-hospital: Glucose and Outcomes (DINGO) study, audited paper-based glucose charts against NBGM-uploaded BG/BK values and BG time-stamps to identify manual transcription inaccuracies. Discrepancy rates, magnitude and potential clinical significance were analysed. 4391 BG and 378 BK NBGM measures from 250 admissions over a two-month period were assessed. Of BG measures, 325 (7.4%) were not recorded in patient charts and 558 (13%) were inaccurate. 302 (54%) inaccurate BGs had potentially clinically significant discrepancies (≥ 0.4 mmol/L). 1570 (36%) BG time-stamps were recorded inaccurately, and 329 (7.5%) were not recorded. 524 (33%) inaccurate BG time-stamps had discrepancies > 15 min. Of BK measures, 153 (41%) were not recorded and 18 (8%) were transcribed inaccurately. Inaccuracy rates were similar across wards and patient groups. Manual transcription of POC BG/BK values and time-stamps, evaluated against blinded concurrent gold-standard digital software, was often inaccurate with potential for clinical harm. Implementation of hospital-wide NBGM systems with automated POC BG/BK upload to EHRs may mitigate manual transcription errors.
Background: Diabetic foot ulcers (DFUs) and lower extremity amputations are major contributors to morbidity and mortality in individuals with diabetes. Among patients undergoing active cancer treatment, the risks are compounded by immunosuppression, peripheral neuropathy, and vascular complications. Even minor foot infections or wounds in these patients can necessitate the suspension of cancer therapy, with potentially lifethreatening consequences. This study evaluated the impaqt of integrating symptom-focused patient education with coordinated podiatric care to reduce DFUs and amputations in this highrisk population with concurrent cancer and diabetes. Methods: A five-year retrospective review was conducted at a National Cancer Institute (NCl)designated comprehensive cancer center as part of the Novel Limb Preservation Initiative. The cohort included patients with Type II diabetes undergoing treatment for prostate, breast, colorectal, lymphoma, leukemia, thyroid, or lung cancers. Patients were assigned targeted educational modules based on self-reported diabetic foot symptoms. Podiatric care was individualized according to each patient's signs and symptoms, including routine diabetic foot examinations and close, timely monitoring when indicated. Results: The intervention yielded a DFU incidence of 2. 8% and an amputation rate of 0. 43%, both lower than national benchmarks. Enhanced patient engagement through diabetic foot symptom-focused education and earlier detection of foot complications-including diabetic foot ssues that may appear minor to laypersons-contributed to these improved outcomes. Conclusion: Integrating diabetic foot symptom-focused education with proactive podiatric monitoring significantly reduced DFUs and amputations in this high-risk population. This model, developed under the Novel Limb Preservation Initiative, offers a scalable strategy for broader implementation, particularly in high-risk communities, including Hispanic, African American, low socioeconomic, and rural populations across the United States.