Evidence regarding sex-related differences in metformin-associated gastrointestinal adverse events (GIAEs) remains limited. This systematic review and meta-analysis aimed to determine whether sex influences the risk of metformin-associated GIAEs. We included observational studies (5 cohorts and 1 case-control) and a randomized controlled trial identified through searches of Ovid MEDLINE, Ovid EMBASE, and CENTRAL from inception to June 2026. Eligible studies reported metformin-associated GIAEs separately in females and males, while studies in which GIAEs could not be attributed to metformin were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for randomized trials. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects meta-analysis. Seven studies (five cohort studies, one case-control study, and one randomized controlled trial) involving 7,968 participants (3,106 females and 4,862 males) were included. Females had significantly higher odds of metformin-associated GIAEs than males (OR 1.85, 95% CI 1.58-2.17), with consistent findings in sensitivity analyses. Females may have a higher risk of metformin-associated GIAEs than males, highlighting the importance of considering sex differences when prescribing metformin and monitoring gastrointestinal intolerance.
AIMS:To examine associations of temporal coordination among 24-h light exposure, physical activity and eating patterns with prevalent diabetes and glycaemic traits. METHODS:We analysed 7,133 adults (1397 with diabetes) from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Phasor analysis generated magnitude and phase for Light-Activity, Light-Energy and Activity-Energy pairs. Survey-weighted models assessed associations with prevalent diabetes and glycaemic traits. RESULTS:In primary Model 3, higher Light-Activity and Activity-Energy magnitudes were associated with lower odds of prevalent diabetes (odds ratio [OR] per 0.01-unit increase 0.964, 95% confidence interval [CI] 0.937-0.993; and 0.889, 0.816-0.968, respectively), whereas the Light-Energy 95% CI included 1.0 (OR 0.910, 95% CI 0.822-1.007). Larger Light-Activity phase was associated with higher odds (OR per 1 h 1.065, 95% CI 1.001-1.133). In Model 4, all three magnitude estimates moved towards 1.0 and their 95% CIs included 1.0. Among participants without diabetes, all three magnitudes were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and 2-h oral glucose tolerance test (OGTT) glucose, but not fasting glucose. CONCLUSIONS:Prospective studies should evaluate temporality, reproducibility and clinical relevance.
On 30 April 2026, the Government of India incorporated diabetes in children within national health policy framework under Rashtriya Bal Swasthya Karyakram (RBSK) Version 2.0 and released national guideline for its implementation. The policy draws substantially on the evidence generated from the West Bengal model which is a sustainable, scalable, government-supported public health model for Type 1 Diabetes (T1D) care. It mandates establishment of dedicated diabetes clinics for children and adolescents in every district hospital across the country, supported by federal funding and implemented through state governments. Evaluation of the West Bengal model demonstrated that structured care delivered through trained non-specialist healthcare teams at secondary-level care (district hospitals) was associated with improved clinical outcomes, improved psychological well-being, and reduced out-of-pocket expenditures. While successful nationwide implementation will largely depend upon workforce capacity building, supply chain maintenance, continued evaluation, and quality assurance, experience from India demonstrates that comprehensive T1D care can be successfully embedded into existing public health systems in low- and middle-income countries (LMICs). The policy provides an important example of how state-level innovation can inform national health policy and may provide useful lessons for strengthening T1D care in other LMICs.
BACKGROUND:We compared the burden and temporal trends of chronic kidney disease due to type 1 diabetes (T1DM-DKD) and type 2 diabetes (T2DM-DKD) in China, the United States, and the United Kingdom from 1990 to 2023 using Global Burden of Disease (GBD) 2023 data. METHODS:We extracted incidence, mortality, and disability-adjusted life-year (DALY) estimates, including 95% uncertainty intervals (UIs), and analysed age-standardized rates by country, age, and sex. Temporal trends were assessed using Joinpoint regression with annual percent change (APC) and average annual percent change (AAPC). Selected T2DM-DKD risk factors were evaluated using the GBD comparative risk assessment framework. RESULTS:China showed overall declines in age-standardized DKD incidence and mortality, whereas T2DM-DKD mortality increased in the USA and UK. In 2023, the T2DM-DKD age-standardized mortality rate was 8.42 per 100,000 (95% UI, 7.02-9.76) in the USA versus 1.27 (95% UI, 0.87-1.68) in China; the corresponding USA AAPC was 4.8% (95% CI, 4.5-5.0). Mortality and DALY rates were highest in the oldest age groups. High body mass index had a comparatively high model-based population-attributable fraction in the USA. CONCLUSIONS:DKD burden patterns differed across countries, supporting region-specific prevention, metabolic risk control, and equitable kidney-protective care.
Beta-cell stress is traditionally viewed as a downstream consequence of autoimmune destruction in type 1 diabetes (T1D). This review examines evidence supporting an alternative interpretation in which intrinsic beta-cell stress precedes and contributes to immune activation. We synthesize findings from experimental models, human islet studies, and recent spatial transcriptomic analyses to describe how endoplasmic reticulum stress, mitochondrial dysfunction, and cGAS-STING signaling may promote major histocompatibility complex class I upregulation, chemokine production, damage-associated molecular pattern release, and neoantigen generation before organized insulitis develops. We further discuss how sustained inflammatory signaling may facilitate tertiary lymphoid structure (TLS) formation, creating a persistent local immune niche that reinforces disease progression. Based on these observations, we present a stage-dependent conceptual framework linking beta-cell stress, innate immune activation, and TLS-mediated stabilization of chronic inflammation. This framework provides a rationale for the limited durability of current immune-targeted therapies and identifies experimentally testable hypotheses using existing human resources, including HPAP, TrialNet, and spatial transcriptomics. Although direct evidence that beta-cell stress precedes immune infiltration in humans remains limited, this perspective offers an integrative framework for interpreting T1D pathogenesis and guiding future translational research.
Diabetic retinopathy (DR) causes preventable vision loss, yet treatments remain reactive. Fenofibrate showed ophthalmic benefits in cardiovascular trials, and LENS (2024) expanded the evidence. Under a pre-registered PRISMA 2020 protocol we searched four databases to June 25, 2026 for randomized trials of fenofibrate reporting an ophthalmic outcome in adults with diabetes, applied RoB 2 and GRADE, and pooled dichotomous outcomes as random-effects risk ratios (RR). Ten studies met inclusion criteria: six completed with extractable results and four ongoing; three completed trials contributed to the primary pooled outcome. All enrolled predominantly type 2 diabetes (one trial 26% type 1, no type-specific estimate). For DR progression, three trials (N = 3,756) gave RR 0.77 (95% CI 0.68-0.88;HKSJ 0.60-0.99; I2 0%; moderate certainty), 45 fewer events per 1,000; stratification gave 0.80 (0.68-0.93) for the LENS composite and 0.70 (0.55-0.90) for ETDRS step-based definitions (difference P = 0.37). Need for retinal treatment fell under the conventional model (RR 0.68, 0.57-0.82) but at low certainty: 90.2% of the weight came from one pre-anti-VEGF-era trial and the HKSJ interval crossed the null (0.42-1.11), so this outcome is not firm evidence about contemporary treatment need. No trial found benefit for visual acuity or function (low certainty); macular edema evidence was not combinable (very low certainty). Venous thromboembolism was increased (RR 1.52, 1.12-2.06), an estimate derived entirely from FIELD (103/4,755 vs 68/4,767). In adults with diabetes, predominantly type 2, fenofibrate slows structural DR progression but is not established as vision-preserving.
AIMS:Postprandial administration of ultra-fast-acting insulin (PP-UFI) may offer greater flexibility for individuals with cystic fibrosis-related diabetes (CFRD). This study evaluated whether PP-UFI provides glycaemic control comparable to standard mealtime fast-acting insulin (MT-FI). METHODS:Adults with CFRD were enrolled in an open-label, multicentre, randomized phase IV crossover trial with a two-sequence, four-period design. Participants received MT-FI or PP-UFI using connected insulin pens for 3-month periods. The primary endpoint was time in range (TIR: 70-180 mg/dL). Mixed-effects models accounted for repeated measures and treatment sequence. RESULTS:Thirty-eight participants were enrolled (mean age: 33 ± 11 years; 56% receiving CFTR modulators), and 34 were included in the intention-to-treat analysis. Baseline TIR was 74% [68-83], time below range (<70 mg/dL) was 4.1% [1.9-6.7], and ppFEV1 was 71 ± 25%. The estimated difference between MT-FI and PP-UFI was + 1.1 percentage points (95% CI: -1.1 to + 3.3; p = 0.316), with no statistically significant difference observed. Formal equivalence was not demonstrated. Other CGM metrics, HbA1c, and insulin doses were comparable between treatments. CONCLUSION:These findings support the potential of postprandial ultra-fast-acting insulin as a flexible treatment option for adults with CFRD.
AIMS:To investigate the association of concurrent diabetes mellitus and poor sleep with cognitive decline in a community-based population. METHODS:Cognitively normal adults aged 40 years or older were followed-up for 4 years. Cognitive decline was defined as a decrease of ≥ 4 points on the Chinese Mini-Mental Status from baseline. Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Logistic regression was employed to evaluate associations of diabetes and poor sleep status with cognitive decline. RESULTS:Among 1218 participants, 30 (2.46%) developed cognitive decline during follow-up. Participants with concurrent diabetes and poor sleep had higher odds of cognitive decline (adjusted OR = 5.74, 95% CI: 1.58 - 18.81). The association of the concurrent presence of poor sleep and diabetes with cognitive decline was evident mainly when poor sleep was defined by poor subjective sleep quality, short sleep duration, low sleep efficiency, frequent sleep disturbances, or severe daytime dysfunction (adjusted ORs, 4.17-10.23; all P < 0.05), rather than prolonged sleep latency. The application of broader criteria for dysglycemia (adjusted OR = 4.10, 95% CI: 1.23 - 12.82) corroborated the robustness of these findings. CONCLUSIONS:The co-occurrence of diabetes and poor sleep was associated with higher odds of cognitive decline, suggesting the clinical potential of integrated interventions in preserving cognitive health.
BACKGROUND:The associations and comparative discrimination of indices integrating inflammation, insulin resistance, and body shape within glycemic-status strata remain uncertain. METHODS:We included 13,867 adults from the 1999-2010 and 2015-2018 National Health and Nutrition Examination Survey. Complex-survey weighted Cox models evaluated CTI, CTI-BMI, CTI-BRI, CTI-WWI, CTI-ABSI, and CTI-WHtR continuously and by weighted quartiles in participants with normal glycemia, abnormal glycemia, or diabetes. Restricted cubic splines, time-dependent receiver operating characteristic curves, interaction tests, and sensitivity analyses were performed. RESULTS:During follow-up, 2,197 all-cause and 687 cardiovascular deaths occurred. Among participants with abnormal glycemia, the hazard ratios per weighted standard deviation for CTI-ABSI were 1.21 (95 % CI, 1.10-1.34) for all-cause mortality and 1.43 (95 % CI, 1.18-1.73) for cardiovascular mortality. Corresponding estimates for CTI-WWI were 1.19 (95 % CI, 1.07-1.33) and 1.49 (95 % CI, 1.20-1.85). CTI-ABSI and CTI-WWI had relatively higher single-marker AUCs in several analyses, but incremental improvements beyond clinical factors were small. Glycemic-status interactions were not statistically significant. CONCLUSIONS:Several CTI-related indices were associated with mortality within glycemic-status strata. However, the findings do not establish effect modification, group-specific applicability, or validated clinical utility. These indices should be considered epidemiological markers.
AIMS:Evaluate the efficacy and safety of iLet Bionic Pancreas (BP) in older adults and individuals with impaired awareness of hypoglycemia (IAH). METHODS:This post hoc analysis used individual participant-level data from the Insulin-Only Bionic Pancreas Pivotal Trial (n = 440; NCT04200313). Eligible participants (n = 96) with type 1 diabetes, aged ≥ 60 years and/or had IAH (Clarke score ≥ 4), were randomized to BP with aspart/lispro (BP-Asp/Lis; n = 45), BP with fast-acting aspart configuration (BP-Fiasp; n = 31), or standard care (SC; n = 20) for 13 weeks. RESULTS:Compared with SC, time-in-range (70-180 mg/dL) significantly increased by 7.49 % (95 % CI: 2.61 to 12.38; ∼1.8 h/day) with BP-Asp/Lis and by 8.28 % (95 % CI: 3.15 to 13.41; ∼2.0 h/day) with BP-Fiasp, driven by reduced hyperglycemia. No significant differences were observed in hypoglycemia exposure. Severe hypoglycemia occurred in four participants (four events) on BP-Asp/Lis and one participant (two events) on SC. One diabetic ketoacidosis event occurred on BP-Fiasp due to an infusion set failure. CONCLUSIONS:In high-risk, clinically vulnerable populations, the BP system significantly improved glycemic control while maintaining safety parity with respect to hypoglycemia risk, providing a resilient therapeutic alternative for vulnerable cohorts.
BACKGROUND:Insulin resistance (IR) is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD), exhibiting tissue-specific effects in the liver, adipose tissue, and muscle. However, the temporal relationships among tissue-specific IR across MASLD status remain unclear. METHODS:We retrospectively identified 491 participants, including 293 without MASLD and 198 with MASLD, who underwent repeated oral glucose tolerance tests and assessment of tissue-specific IR indices between June 2014 and December 2025. Cross-lagged path analysis was performed separately according to baseline MASLD status to examine temporal associations among hepatic IR, adipo-IR, and muscle IR. Logistic regression was used to explore baseline factors associated with persistent or progressive IR. RESULTS:After a median interval of 22 months (range, 12-32 months), 63 of 293 participants without MASLD (21.5%) developed MASLD, while 47 of 198 participants with MASLD (23.7%) transitioned to an elevated FIB-4 category (>1.3). In the fully adjusted model, baseline hepatic IR was associated with subsequent adipo-IR (ρ1 = 0.303, P < 0.01) and muscle IR (ρ2 = -0.211, P < 0.001) in participants without MASLD. In participants with MASLD, hepatic IR (ρ2 = -0.195, P < 0.01) and adipo-IR (ρ4 = -0.184, P < 0.05) were associated with subsequent muscle IR, while baseline muscle IR was associated with subsequent hepatic IR (ρ5 = 0.084, P < 0.05). Body mass index (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.13), HOMA-IR (OR, 1.26; 95% CI, 1.07-1.47), and CT attenuation value (OR, 0.97; 95% CI, 0.94-0.99) were associated with persistent or progressive IR (all P < 0.05). CONCLUSION:The temporal relationships among tissue-specific IR differed according to MASLD status. Hepatic IR preceded peripheral IR in participants without MASLD, whereas more multidirectional relationships were identified in those with MASLD. These findings are hypothesis-generating and do not establish a causal sequence.
AIMS:Severe hypoglycemia is an important adverse event in type 2 diabetes, particularly among older adults and clinically vulnerable patients. However, recent real-world trends in hypoglycemia requiring hospitalization in Japan are insufficiently characterized. METHODS:We conducted a retrospective cross-sectional study by using Japanese hospital-based claims data for 2009-2022. Patients receiving glucose-lowering medications for type 2 diabetes were included (N = 1,391,948). The primary outcome was hospitalization for hypoglycemia, defined using codes for diagnosis, same-day hospitalization, and intravenous administration of 50% glucose. Secondary outcomes were nocturnal hospitalization and the requirement of emergency transport. Annual frequencies were described, and adjusted risk ratios were estimated using modified Poisson regression analysis. RESULTS:Overall, 7,157 patients were hospitalized for hypoglycemia. The annual frequency decreased from 0.41% in 2009 to 0.21% in 2022; the greatest decline was among patients aged ≥ 75 years, who continued to account for the majority of hospitalizations. Older age and lower body mass index were associated with all hypoglycemia-related outcomes, as were insulin, pioglitazone, glucagon-like peptide-1 receptor agonists, alpha-glucosidase inhibitors, and sulfonylureas. In the sensitivity analysis, impaired kidney function was associated with an increased risk. CONCLUSIONS:Hypoglycemia-related hospitalization declined in Japan during 2009-2022, with the residual burden remaining concentrated among older adults.
AIMS:Comorbidities are common at diabetes onset and may influence long-term outcomes. We examined national trends in the prevalence, number, and multimorbidity patterns among U.S. adults with newly ascertained diabetes, distinguishing concordant metabolic risk factors, concordant vascular diseases, and discordant conditions. METHODS:We analyzed National Health and Nutrition Examination Survey data (1999-August 2023) for adults (≥20 years) with newly ascertained diabetes (diagnosed at the survey or ≤2 years prior; n = 4,243). Age-adjusted prevalence of 13 comorbidities, mean comorbidity count, and multimorbidity patterns were estimated across three periods. Trends were assessed using logistic and linear regression and pattern distributions using chi-square tests. RESULTS:Obesity increased from 58.3% (1999-2006) to 71.0% (2015-2023) (p = 0.0003); Chronic lung disease rose from 15.4% to 22.8% (p = 0.007). Chronic kidney disease (∼30%) and cardiovascular disease (11.8%-14.1%) were stable. Arthritis (∼40%), sleep disorders (29.2%-38.5%), and dental caries (∼30%) were common but stable. The mean comorbidity count increased from 4.25 to 4.51 (p = 0.038), with greater overlap of concordant and discordant conditions (p = 0.008). CONCLUSIONS:From 1999 to 2023, obesity, chronic lung disease, and total number of comorbidities increased among adults with new diabetes. Multimorbidity patterns increasingly encompassed both concordant and discordant conditions, potentially complicating management and worsening outcomes.
BACKGROUND:The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. METHODS:Clinicopathological data from 295 biopsy-proven DKD patients were collected and classified into normoalbuminuric (UACR < 30 mg/g, n = 25), microalbuminuric (UACR 30-300 mg/g, n = 26), and macroalbuminuric (UACR > 300 mg/g, n = 244) groups. Laser microdissection combined with mass spectrometry (LMD/MS) was used to analyze glomerular and proximal tubule proteomics in 5 patients per DKD subgroup and 5 control subjects. Associations with clinical features were examined. RESULTS:Glomerular proteomic analysis revealed that oxidative stress and metabolic pathways (UQCRC1) were upregulated in NADKD group, whereas the complement and coagulation cascades (C3, C5, C6, C9, CFH, CFHR1) were significantly upregulated in the microalbuminuric and macroalbuminuric DKD groups. The proximal tubule proteomics analysis showed that oxidative phosphorylation-related proteins (SDHA, CYCS, UQCRQ) were upregulated in NADKD, and collagen I related proteins (COL1A1, COL1A2) were significantly upregulated. CONCLUSION:Oxidative stress and mitochondrial dysfunction are involved in the progression of NADKD, lesions predominantly located in the tubulointerstitium. The complement pathway participates in the pathogenesis and progression of albuminuric DKD (ADKD). These divergent molecular profiles suggest that NADKD and ADKD may reflect different pathophysiological mechanisms and have important implications for therapeutic strategies in diabetes management.
AIM:To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12 months. METHODS:This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10 mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12 months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS:Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7 dB/m; mean change - 71.02 dB/m, 95% CI: -63.4 to - 78.6; p < 0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28 kPa; mean change - 1.31 kPa, 95% CI: -0.92 to - 1.70; p < 0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS:Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12 months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.
AIMS:To examine vascular alterations across cardiovascular-kidney-metabolic (CKM) domains and characterize sex differences in adults with type 2 diabetes (T2D) from the Qatar Biobank. METHODS:Cross-sectional analysis of 5,144 Qatar Biobank adults with T2D. Eight vascular outcomes were assessed: pulse wave velocity (PWV), pulse pressure, carotid intima-media thickness and its variability, resistivity index, and pulsatility index. Three CKM domains were defined: metabolic, cardiovascular, and renal. Hierarchical linear regression and independent-samples t-tests were used. RESULTS:Mean PWV was 15.06 m/s; 87.8% of participants exceeded the pathological arterial stiffness threshold of 10 m/s. Pathological PWV prevalence was higher in females, though males exceeded females at higher percentiles. Structural and Doppler outcomes were higher in females before adjustment but reversed after multivariable adjustment, reflecting confounding by adiposity and comorbidity burden. Age was the strongest predictor across all eight models. Waist-hip ratio, not body mass index, independently predicted PWV, and hypertension was the broadest cardiovascular predictor. Despite the smallest subgroup, the renal domain showed the largest absolute differences in PWV and pulse pressure. CONCLUSIONS:Vascular alterations were prevalent across CKM-related domains in adults with T2D. Findings suggest that sex-specific reference values and domain-stratified vascular assessment may improve cardiovascular risk evaluation in this population.
OBJECTIVE:To estimate the global burden of type 2 diabetes mellitus (T2DM) attributable to dietary risks among working-age adults from 1990 to 2023, stratified by sex, age, region, and Socio-Demographic Index (SDI). Because Global Burden of Disease (GBD) 2023 data are not disaggregated for ages 15-24, analyses were restricted to adults aged 25-64 years, the core working-age group. STUDY DESIGN:GBD 2023 data from 204 countries and territories were analyzed. Age-standardized mortality (ASMR) and disability-adjusted life-year rates (ASDR) attributable to seven dietary risks were estimated using population-attributable fractions and joinpoint regression. RESULTS:During 1990-2023, global ASMR rose from 17.1 to 21.5 per 100,000 (average annual percentage change [AAPC] 0.69%), accelerating after 2010, and ASDR rose from 695.9 to over 800 per 100,000 (AAPC 0.50%). Sugar-sweetened beverages and processed meat were the fastest-growing risks; the low-fiber burden declined slightly. Males bore higher and faster-growing burdens. Pacific Island nations had the highest rates; Eastern Europe and the Middle East grew fastest. Crude DALYs rose most among 25-29-year-olds, largely reflecting demographic change. CONCLUSION:Diet-related T2DM burden is rising among working-age adults, with sugar-sweetened beverages and processed meats growing fastest. Targeted interventions are urgently needed in high-burden regions, particularly for males and younger adults.
Ashwagandha (Withania somnifera) may affect glycemic control, although findings from randomized trials remain inconsistent. This systematic review and meta-analysis evaluated its effects on fasting blood glucose (FBG) and glycated hemoglobin (HbA1c). Cochrane Library, PubMed, Scopus, and Web of Science were searched from inception through August 12, 2026. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were estimated using random-effects models. Subgroup, meta-regression, nonlinear dose-response, sensitivity, and publication-bias analyses were performed, and evidence certainty was assessed using GRADE. Eleven trials involving 667 participants were included. Across 15 effect estimates, Ashwagandha modestly reduced FBG compared with placebo (WMD, -3.09 mg/dL; 95% CI, -5.61 to -0.58), with substantial heterogeneity. The HbA1c estimate, based on three trials, was imprecise and inconclusive (WMD, -0.05%; 95% CI, -0.47 to 0.36). Exploratory subgroup analyses suggested variation in FBG effects by intervention duration and dose, but did not establish an advantage for any duration or dose. Nonlinear analyses showed no association with dose or intervention duration. Certainty of evidence was very low for both outcomes. Ashwagandha may modestly reduce FBG, but substantial heterogeneity and very low certainty preclude clinical recommendations.
OBJECTIVE:To assess the association between Colquhounia Root Tablet (CRT), a Tripterygium hypoglaucum-derived immune-metabolic modulator, and kidney outcomes in type 2 diabetic kidney disease (DKD) patients with heavy proteinuria despite guideline-directed therapy (renin-angiotensin system blockade, SGLT2 inhibitors, finerenone). METHODS:A retrospective propensity score-matched cohort study was conducted using hospital-based electronic health records. Patients with heavy-proteinuric type 2 DKD (UACR > 300 mg/g) were matched 1:1 (159 pairs). The primary endpoint was major adverse kidney events (MAKE: ≥57% sustained eGFR decline, end-stage renal disease, or kidney-related death), analyzed using multivariable-adjusted flexible parametric survival models. RESULTS:The matched cohort had a median UACR of 1818 mg/g; 40.2% were classified as KDIGO very high risk. Over 5 years, CRT use was associated with lower MAKE incidence (52.6% vs 70.9%; adjusted HR 0.60; 95% CI, 0.43-0.85; p = 0.004), slower annual eGFR decline (-5.08 vs - 7.05 mL/min/1.73 m2/year; p < 0.001), and greater UACR reduction at 12 months (-52.8% vs 1.8%; p < 0.001), with comparable safety. CONCLUSION:Adjunctive CRT was associated with improved kidney outcomes in high-risk heavy-proteinuric DKD, supporting future randomized trials targeting immune-metabolic phenotypes with persistent proteinuria and residual risk.
AIMS:To examine the prospective association between hemoglobin glycation index (HGI) and incident chronic lung disease (CLD) in individuals with cardiovascular-kidney-metabolic syndrome (CKM) stages 0-3. METHODS:We examined the association between HGI and incident CLD in the UK Biobank and CHARLS. After exclusions, 275,389 and 7,042 participants were included, respectively. HGI was calculated as observed minus predicted HbA1c based on cohort-specific fasting blood glucose-HbA1c regression equations. Cox models, Kaplan-Meier analysis, restricted cubic spline models, two-piecewise Cox regression, and subgroup analyses were performed. RESULTS:During follow-up of 7.29 years in UK Biobank and 9.00 years in CHARLS, 20,273 and 603 CLD cases occurred, respectively. Higher HGI was associated with increased CLD risk in both cohorts. In the fully adjusted model, each 1-SD increase in HGI was associated with higher CLD risk in the UK Biobank (HR 1.044, 95% CI 1.031-1.057) and CHARLS (HR 1.097, 95% CI 1.020-1.181). Compared with the lowest quartile, highest quartile had increased CLD risk in the UK Biobank (HR 1.118, 95% CI 1.074-1.165) and CHARLS (HR 1.414, 95% CI 1.126-1.776). Exploratory subgroup analyses suggested possible heterogeneity by diabetes status, although the interaction was not robust after correction for multiple testing. CONCLUSIONS:Higher baseline HGI was prospectively associated with increased CLD risk among adults aged ≥45 years with CKM stages 0-3, with directionally consistent findings across the UK Biobank and CHARLS. These findings support further evaluation of HGI as a research-based epidemiological marker for potential risk stratification.
