Diabetes Research And Clinical Practice[JOURNAL]
Sun
200 papers
Gut microbiota-mediated metabolic dysregulation in type 2 diabetes and metabolic syndrome: emerging therapeutic targets beyond glycaemic control.
Sharma H, Tyagi S, Verma S … +2 more , Ghosh S, Pande MS
Diabetes Res Clin Pract · 2026 Jun · PMID 42086084 · Publisher ↗
Metabolic diseases, particularly type 2 diabetes mellitus (T2DM) and obesity, have been traditionally understood through glucose-centric models. However, hyperglycaemia is a downstream consequence of systemic immune-meta...
Metabolic diseases, particularly type 2 diabetes mellitus (T2DM) and obesity, have been traditionally understood through glucose-centric models. However, hyperglycaemia is a downstream consequence of systemic immune-metabolic dysregulation, with the gut microbiota acting as a central upstream regulator through defined molecular signalling pathways. This review examines four principal microbiota-host signalling axes through which ecological disruption drives systemic metabolic disease: short-chain fatty acid (SCFA) depletion impairing free fatty acid receptor (FFAR2/FFAR3) and AMP-activated protein kinase (AMPK) signalling; altered bile acid (BA) biotransformation perturbing farnesoid X receptor (FXR) and TGR5 signalling; increased intestinal permeability facilitating lipopolysaccharide (LPS) translocation and Toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) activation; and diminished indole production reducing aryl hydrocarbon receptor (AhR)-driven interleukin-22 (IL-22) secretion. Therapeutic strategies targeting these pathways, including SCFA prodrugs, FXR modulators, TGR5 agonists, and next-generation probiotics, offer disease-modifying potential beyond glycaemic lowering and highlight the need for a multidimensional clinical endpoint framework spanning inflammatory, hepatic, and barrier biomarkers to enable comprehensive translational evaluation of microbiota-directed therapies.
An observational study on glycemic trajectories during ascent, stay, and descent in a 45-day high-altitude exposure.
Zhang B, Sun M, Yang Z … +5 more , Wang T, Xu R, Shi L, Wang Y, Peng W
Diabetes Res Clin Pract · 2026 Jul · PMID 42086083 · Publisher ↗
AIMS: To characterize glycemic dynamics and heterogeneity in response patterns during a 45-day high-altitude expedition among healthy adults. METHODS: In this longitudinal observational study, eight healthy adults underw...
AIMS: To characterize glycemic dynamics and heterogeneity in response patterns during a 45-day high-altitude expedition among healthy adults. METHODS: In this longitudinal observational study, eight healthy adults underwent continuous glucose monitoring (CGM) during ascent (2,800 to 4,531 m), stay, and descent. Glycemic metrics (mean glucose, variability indices, time-in-range) were analyzed across altitude-defined phases. Unsupervised clustering was employed to identify glycemic response patterns. RESULTS: Mean glucose exhibited a mild U-shaped trend, with transient elevation and peak glycemic variability (CV = 17.3%) at extreme altitude. Time-in-range remained >97%. Cluster analysis revealed two distinct patterns: a stable, low-variability group (Cluster 1) and a high-variability group (Cluster 2) with amplified excursions and delayed recovery. CONCLUSIONS: Short-term high-altitude exposure induces mild, reversible disturbances in glucose regulation, with significant inter-individual heterogeneity. CGM effectively captures these dynamic changes and identifies distinct adaptive patterns, highlighting its utility for monitoring metabolic stress and population-specific responses in extreme environments.
Melatonin supplementation improves insulin resistance markers but not fasting glucose: a systematic review and meta-analysis of randomized controlled trials.
Dias GZT, Tessarin GWL, Ferreira RL … +4 more , de Souza KB, Toro LF, Nobumoto ACTY, Santos RM
Diabetes Res Clin Pract · 2026 Jul · PMID 42070664 · Publisher ↗
This study evaluated whether oral melatonin supplementation influences glycemic outcomes in humans through a systematic review and meta-analysis of randomized controlled trials (RCTs). A systematic search of major electr...
This study evaluated whether oral melatonin supplementation influences glycemic outcomes in humans through a systematic review and meta-analysis of randomized controlled trials (RCTs). A systematic search of major electronic databases was conducted to identify RCTs evaluating the effects of melatonin supplementation on metabolic outcomes in adults. Studies reporting fasting glucose, glycated hemoglobin (HbA1c), fasting insulin, or homeostatic model assessment of insulin resistance (HOMA-IR) were included. Data were pooled using a random-effects model. Heterogeneity was assessed using the I statistic, and meta-regression analyses were performed to explore potential moderators. Statistical analyses were conducted using Jamovi software. Thirty-one RCTs were included in this systematic review. Quantitative synthesis comprised 27 studies reporting fasting glucose, nine studies reporting HbA1c, seven studies reporting fasting insulin, and four studies reporting HOMA-IR. Melatonin doses ranged from 1 to 10 mg/day, with intervention durations between 14 and 365 days. The meta-analysis showed no significant reduction in fasting glucose levels. However, improvements were observed in secondary metabolic outcomes related to glycemic control and insulin resistance, including HbA1c, fasting insulin, and HOMA-IR. Melatonin supplementation did not significantly reduce fasting glucose but may improve markers of glycemic control and insulin sensitivity, suggesting a modulatory role in metabolic regulation.
Untargeted metabolomics and mendelian randomization analysis identify adrenic acid as a novel biomarker of Type 2 diabetes mellitus.
Wang F, Li X, Yan S … +7 more , Xu Y, Wu S, Zhu Y, Chen H, Meng Z, Li B, Yao Y
Diabetes Res Clin Pract · 2026 Jun · PMID 42070663 · Publisher ↗
PURPOSE: Given the differences between Chinese T2DM patients and those of other ethnicities, understanding the metabolic contributions in this population is essential. This study aimed to identify T2DM-associated metabol...
PURPOSE: Given the differences between Chinese T2DM patients and those of other ethnicities, understanding the metabolic contributions in this population is essential. This study aimed to identify T2DM-associated metabolic biomarkers through clinical untargeted metabolomics and mendelian randomization (MR). METHODS: This study included 120 Chinese participants, including 60 patients with T2DM and 60 control subjects. We employed ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for non-targeted metabolomics analysis of plasma metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify T2DM-related metabolites. Integration of metabolomics and MR data identified novel key biomarkers for T2DM. RESULTS: LC-MS/MS-based untargeted metabolomics identified 71 up-regulated and 37 down-regulated metabolites in the Chinese T2DM patients. In MR analysis, 52 metabolites exhibited causal associations with the risk of T2DM. Integrating metabolomic analysis with genetic evidence-based causal inference collectively confirmed that higher adrenic acid (AdA) was associated with an increased risk of T2DM and positively correlated with fasting blood glucose (FBG). The main impacted metabolic pathways were unsaturated fatty acids biosynthesis and linoleic acid metabolism. CONCLUSIONS: Increased plasma AdA level was associated with higher FBG and an elevated risk of T2DM, suggesting that AdA represents a probable biomarker for T2DM.
DPP-4 inhibitors in current diabetes care: their foundational role in treating to target.
Avogaro A, Fiaccadori E, Rizzo MR
Diabetes Res Clin Pract · 2026 Jul · PMID 42070662 · Publisher ↗
Despite major advances in glucose-lowering therapies, a substantial proportion of individuals with type 2 diabetes (T2DM) do not achieve recommended glycemic targets, maintaining a high risk of microvascular and macrovas...
Despite major advances in glucose-lowering therapies, a substantial proportion of individuals with type 2 diabetes (T2DM) do not achieve recommended glycemic targets, maintaining a high risk of microvascular and macrovascular complications. While current guidelines prioritize agents with proven cardiovascular and renal benefits (treat-to-benefit), optimal glycemic control (treat-to-target) remains a cornerstone of diabetes management. This review supports an integrated therapeutic framework in which both strategies are pursued in parallel and examines the role of dipeptidyl peptidase-4 inhibitors (DPP-4is) within this context. DPP-4is provide clinically meaningful HbA1c reductions, approximately 0.6-1.1%, with a low risk of hypoglycemia, weight neutrality, and a favorable tolerability profile. Cardiovascular outcome trials have established their cardiovascular safety, and they are particularly suitable as add-on treatment to metformin, SGLT-2 inhibitors, or insulin, enabling safe intensification to achieve glycemic targets while maintaining cardiorenal-protective regimens. DPP-4is tolerability makes them specifically indicated for older patients. In contemporary diabetes care, DPP-4is-particularly sitagliptin-remain a versatile option bridging treat-to-target and treat-to-benefit paradigms to support comprehensive cardiovascular-kidney-metabolic (CKM) reduction in T2DM.
Postural control in type 2 diabetes mellitus: the role of diabetic neuropathy.
Madsen MD, Arulanandam D, Svendsen CL … +7 more , Rytter Pedersen SW, Graversen JL, Kvist AV, Hirata RP, Vestergaard P, Røikjer J, Rasmussen NH
Diabetes Res Clin Pract · 2026 Jun · PMID 42070661 · Publisher ↗
AIM: To examine postural control in people with type 2 diabetes mellitus (T2DM) with and without diabetic neuropathy (DN) using center of pressure (CoP) measures under varying sensory and cognitive conditions. METHOD: In...
AIM: To examine postural control in people with type 2 diabetes mellitus (T2DM) with and without diabetic neuropathy (DN) using center of pressure (CoP) measures under varying sensory and cognitive conditions. METHOD: In this cross-sectional study, adults aged ≥ 40 years with T2DM for at least one year. Neuropathy was classified as severe peripheral neuropathy (DPN) or autonomic neuropathy (DAN), defined by vibration perception threshold ≥ 50 V, ≥2 abnormal cardiac autonomic reflex tests, or orthostatic hypotension. Postural control was assessed by CoP and CoP under different sensory and cognitive conditions. Regression analyses were adjusted for demographic factors, physical performance, and fall-associated medication. Exploratory analyses were performed by neuropathy subtype. RESULTS: 99 participants were included, 49 with DN and 50 without. The DN group was older (66.8 vs. 60.8 years) and more often male (75.5% vs. 52%). DN was associated with greater CoP (β = 0.56, p = 0.006). Exploratory analyses suggested larger CoP in participants with DAN alone (β = 0.76, 95% CI 0.36-1.16) or combined with DPN (β = 0.70, 95% CI 0.13-1.34), whereas DPN alone was not associated with CoP. CONCLUSION: DN was linked to impaired postural control, with indications of differences by neuropathy subtype. CoP assessment may help identify people with T2DM at increased risk of falls.
Association between famine exposure and type 2 diabetes mellitus over the last three decades: a systematic review and meta-analysis.
Turkar A, Purkayastha K, Kumar RS … +5 more , Tanwar S, Deo V, Shalini S, Tomar M, Pati S
Diabetes Res Clin Pract · 2026 Apr · PMID 42069307 · Publisher ↗
Early-life nutritional deprivation from famine may increase lifelong vulnerability to Type 2 Diabetes Mellitus (T2DM). This Systematic Review and Meta-Analysis evaluated studies published over the past three decades to a...
Early-life nutritional deprivation from famine may increase lifelong vulnerability to Type 2 Diabetes Mellitus (T2DM). This Systematic Review and Meta-Analysis evaluated studies published over the past three decades to assess and appraise the association between famine exposure across developmental stages and T2DM risk. PubMed, Embase, Web of Science, and the Cochrane Library identified observational studies published between 1995 and 2025. Studies reporting risk estimates or data enabling calculation of risk ratios (RRs) were included, followed by pooled estimates were generated. Methodological quality was assessed using the Newcastle-Ottawa Scale. Subgroup analyses, meta-regression and sensitivity analyses were conducted to explore heterogeneity. Of 6311 identified articles, 40 met the inclusion criteria. Overall, famine exposure was associated with 43 % higher risk of T2DM (95 % CI: 1.30-1.56; I = 96.7 %). The pooled risk increased to 47 % in studies published between 2016 and 2025. Longer famine duration (RR = 1.79) and females (RR = 1.52) showed comparatively higher risk. Higher famine severity and exposures during the fetal stage indicated greater susceptibility. Thus, famine exposure is consistently associated with increased risk of T2DM, particularly with prolonged or severe exposure and among women. Nutritional deprivation during key developmental periods may have lasting metabolic effects.
Temporal trends in macrovascular complications in young-onset diabetes in Korea: A nationwide population-based study.
Kim HY, Ji E, Kim J
Diabetes Res Clin Pract · 2026 Jun · PMID 42061622 · Publisher ↗
AIMS: To examine temporal trends and risk factors for macrovascular complications in individuals with young-onset diabetes. METHODS: Data from the Korean Health Insurance Review and Assessment Service (2008-2021) were an...
AIMS: To examine temporal trends and risk factors for macrovascular complications in individuals with young-onset diabetes. METHODS: Data from the Korean Health Insurance Review and Assessment Service (2008-2021) were analyzed for individuals diagnosed with diabetes before age 30 years. Age-standardized incidence and prevalence were estimated using Poisson regression. Time-dependent Cox models assessed risk factors, and segmented regression evaluated changes during the COVID-19 pandemic. RESULTS: We included 6,432 individuals with type 1 diabetes and 71,615 with type 2 diabetes. Between 2008 and 2021, the incidence of macrovascular complications declined from 72.1 to 35.5 per 10,000 persons in type 1 diabetes and from 169.5 to 71.4 in type 2 diabetes, whereas prevalence remained substantial. In type 1 diabetes, older age at diagnosis, low socioeconomic status, hypertension, dyslipidemia, and comorbidity burden increased risk; in type 2 diabetes, older age at diagnosis, low socioeconomic status, hypertension, mental and thyroid disorders, and comorbidity burden increased risk. During COVID-19, incidence increased only in type 2 diabetes. CONCLUSIONS: Despite declining incidence, macrovascular complications remain a substantial burden in young-onset diabetes, particularly in early adulthood and type 2 diabetes, highlighting the need for early cardiovascular risk management.
Diabetes-dependent association between metabolic score for visceral fat and chronic kidney disease: findings from a longitudinal cohort study.
Kwon YJ, Song Y, Lee JW … +2 more , Heo SJ, Lee JE
Diabetes Res Clin Pract · 2026 Jun · PMID 42061621 · Publisher ↗
AIMS: Metabolic dysfunction drives chronic kidney disease (CKD). Although the metabolic score for visceral fat (METS-VF) emerged as a novel marker of cardiometabolic health, its association with CKD remains unclear. We i...
AIMS: Metabolic dysfunction drives chronic kidney disease (CKD). Although the metabolic score for visceral fat (METS-VF) emerged as a novel marker of cardiometabolic health, its association with CKD remains unclear. We investigated the association between METS-VF and incident CKD and determined whether this relationship varies according to diabetes status. METHODS: This longitudinal study analyzed data from 8,092 participants in the Korean Genome and Epidemiology Study. METS-VF was categorized into quartiles. Hazard ratios (HRs) for CKD development were estimated using Cox proportional hazards model and underwent multivariate adjustment. RESULTS: During a mean follow-up of 12.8 years, 2,202 incident CKD cases were identified. Compared to Q1, Q4 was associated with an increased CKD risk in the unadjusted model (HR: 2.941; 95% CI: 2.591-3.339; P < 0.001) which persisted after multivariate adjustment (adjusted HR: 1.373; 95% CI: 1.201-1.571; P < 0.001). Subgroup analyses revealed the association between METS-VF and incident CKD was significant only in individuals with normoglycemia. CONCLUSIONS: Higher METS-VF was associated with increased risk of CKD development; however, it was confined to individuals with normal glucose tolerance. This suggests METS-VF may serve as an exploratory marker for stratified risk assessment for early CKD risk before the onset of glucose dysregulation, emphasizing the critical window for early metabolic intervention.
Cardiovascular outcomes with thiazolidinediones and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus undergoing peripheral artery revascularization.
Roh JW, Jeon J, Yoo J … +4 more , Baik M, Heo SJ, Cho DK, Kim J
Diabetes Res Clin Pract · 2026 Jun · PMID 42055167 · Publisher ↗
AIMS: The comparative effectiveness of anti-diabetic agents in patients with type 2 diabetes mellitus (T2DM) undergoing peripheral artery revascularization remains unclear. METHODS: Using the Korean National Health Insur...
AIMS: The comparative effectiveness of anti-diabetic agents in patients with type 2 diabetes mellitus (T2DM) undergoing peripheral artery revascularization remains unclear. METHODS: Using the Korean National Health Insurance Claims database (2015-2023), we identified patients with T2DM who underwent peripheral artery revascularization (endovascular or surgical). To control for baseline differences, we utilized 1:3 propensity score matching to compare thiazolidinediones (TZD) vs. dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) vs. DPP-4i. Stratified Cox regression model assessed the risk for the primary outcome, defined as a composite of major adverse limb events (repeated revascularization or amputation), stroke, myocardial infarction, admission for heart failure, and all-cause death. RESULTS: The primary outcome occurred in 49.3% of TZD users versus 55.5% of DPP-4i users (HR 0.74; 95% CI 0.63-0.86; p < 0.001) and in 39.7% of SGLT-2i users versus 52.2% of DPP-4i users (HR 0.88; 95% CI 0.79-0.98; p = 0.015). Regarding secondary outcomes, TZD users were associated with lower risks of major adverse limb events, and all-cause death compared with DPP-4i users. SGLT-2i treatment was associated with reduced all-cause death. CONCLUSIONS: Among patients with T2DM undergoing peripheral artery revascularization, TZD and SGLT-2i were associated with favourable clinical outcomes compared to DPP-4i.
Experiences of type 2 diabetes stigma in healthcare settings: a mixed-methods systematic review.
Ekpor E, Manallack S, Garza M … +2 more , Speight J, Holmes-Truscott E
Diabetes Res Clin Pract · 2026 Jun · PMID 42055166 · Publisher ↗
International consensus highlights the urgent need to address diabetes stigma in healthcare. This systematic review synthesised qualitative and quantitative evidence to provide context-specific insights into type 2 diabe...
International consensus highlights the urgent need to address diabetes stigma in healthcare. This systematic review synthesised qualitative and quantitative evidence to provide context-specific insights into type 2 diabetes (T2D) stigma in healthcare settings. We searched PubMed, CINAHL, and PsycINFO (from inception to December 2025). Data were analysed thematically using a hybrid deductive-inductive coding approach guided by the Health Stigma and Discrimination Framework (HSDF), examining four key domains of stigma: manifestations, drivers/facilitators, markers, and impacts. Sixty-one articles from 32 countries were included. Individuals with T2D perceived, experienced, anticipated, and internalised T2D stigma, perpetuated through healthcare professionals' (HCPs') communication, attitudes, and practices. T2D stigma was driven by negative emotional reactions, stereotypes, authoritarianism, and lack of knowledge; and facilitated by overly simplistic care models and healthcare-related media misrepresentation. Negative impacts spanned psychosocial well-being, health-seeking behaviours, quality of care, and interpersonal relationships with HCPs. People with T2D called for HCPs and system-level reforms to foster stigma-free T2D healthcare. These findings strengthen the understanding of T2D stigma in healthcare, including its pervasiveness and consequences, and reveal actionable drivers and facilitators, which can be used to develop targeted interventions and guidance towards stigma-free T2D care.
PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.
Zhu Y, Hocher B, Liu F
Diabetes Res Clin Pract · 2026 Jun · PMID 42049098 · Publisher ↗
Protein arginine methyltransferase 1 (PRMT1) is best known as a nuclear epigenetic writer that deposits the activating H4R3me2a mark. However, PRMT1 also methylates diverse non‑histone substrates across multiple cellular...
Protein arginine methyltransferase 1 (PRMT1) is best known as a nuclear epigenetic writer that deposits the activating H4R3me2a mark. However, PRMT1 also methylates diverse non‑histone substrates across multiple cellular compartments, and this review moves beyond chromatin‑centric models to provide a substrate‑driven mechanistic framework in kidney and metabolic diseases. We analyze four validated substrate axes: FoxO1 in gluconeogenesis, BRD4 in fibrosis, UBE2m in fatty acid metabolism, and RelA in inflammation. These examples illustrate how PRMT1 integrates metabolic, inflammatory and fibrotic signals in a cell‑type‑specific manner. A key insight is functional pleiotropy: PRMT1 exerts opposing roles-restraining lipolysis in white adipose tissue while enabling thermogenesis in brown fat, and suppressing NF‑κB in renal tubules while promoting pro‑inflammatory macrophage polarization in the liver. This complexity challenges the view of PRMT1 as uniformly pro‑pathogenic. We critically evaluate the inhibitor landscape, including the terminated clinical trial of GSK3368715, and identify major translational barriers. We conclude that realizing therapeutic potential in chronic kidney and metabolic diseases requires a shift from broad inhibition toward context‑selective modulation-through substrate‑selective inhibitors, tissue‑specific delivery and biomarker‑guided strategies.
Impact of sodium-glucose cotransporter-2 inhibitors on clinical outcomes in patients with type 1 diabetes after dialysis-requiring acute kidney injury: a real-world cohort study.
Wang CA, Wang WJ, Chen JY … +2 more , Jiang ZH, Wu VC
Diabetes Res Clin Pract · 2026 Jun · PMID 42049097 · Publisher ↗
AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have shown significant cardiovascular and kidney benefits, but their role in T1D with acute kidney disease (AKD) remains uncertain. METHODS: This propensity-scor...
AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have shown significant cardiovascular and kidney benefits, but their role in T1D with acute kidney disease (AKD) remains uncertain. METHODS: This propensity-score matching cohort study utilized data from the TriNetX Network, including patients aged ≥18 years with T1D after dialysis requiring acute kidney disease (AKI) and were discharged from hospitals between 2012 and 2024. The primary outcomes were all-cause mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs), analyzed using Cox proportional hazards regression models. RESULTS: Among 16,680 patients with T1D and AKD, 614 (3.74%) patients received SGLT-2is, and matched with non-users. After a median follow-up of 1.7 years, SGLT-2i use was associated with lower all-cause mortality (aHR, 0.49; 95% CI, 0.36-0.71) and MAKEs (aHR, 0.53; 95% CI, 0.34-0.82), but no significant difference in MACEs (aHR, 0.86; 95% CI, 0.59-1.25). Genital infections and volume depletion were more frequent, without significant increase in diabetic ketoacidosis, urinary tract infections, or hypoglycemia. CONCLUSIONS: In this study, SGLT-2i use was associated with improved kidney outcomes and reduced all-cause mortality in T1D patients with AKD. These findings suggest potential kidney and survival benefits, warranting further prospective validation.
Beyond HbA1c: Albumin-corrected fructosamine is associated with diabetic retinopathy in well-controlled type 2 diabetes.
Long Q, Liu Z, Kang S … +5 more , He Q, Wang H, Qi X, Lin S, Zhu P
Diabetes Res Clin Pract · 2026 Jun · PMID 42049096 · Publisher ↗
AIMS: Diabetic retinopathy (DR) can occur in type 2 diabetes (T2DM) despite well-controlled glycaemia (HbA1c <7.0%), indicating that glycation-related factors beyond HbA1c may contribute to its development. Albumin-corre...
AIMS: Diabetic retinopathy (DR) can occur in type 2 diabetes (T2DM) despite well-controlled glycaemia (HbA1c <7.0%), indicating that glycation-related factors beyond HbA1c may contribute to its development. Albumin-corrected fructosamine (AlbF) may provide complementary information on glycaemic exposure relevant to DR risk. METHODS: This retrospective cross-sectional study included 1,090 T2DM patients. AlbF was calculated as serum fructosamine/albumin ratio. DR was assessed by standardized ophthalmic examination. Multivariable logistic regression examined the association between AlbF and DR, adjusting for demographic, metabolic, and clinical covariates. Subgroup analyses were performed by HbA1c level. RESULTS: Higher AlbF was independently associated with DR. In fully adjusted models, each 10 μmol/g increase in AlbF was associated with 65% higher odds of DR (OR 1.65; 95% CI 1.40-1.95). The highest versus lowest AlbF tertile showed nearly fivefold higher odds (OR 4.77; 95% CI 2.99-7.60). The association remained significant in patients with HbA1c <7.0%. Adding AlbF modestly improved discrimination (ΔAUC=0.045; P=0.002), but this improvement should be interpreted cautiously. CONCLUSIONS: AlbF is independently associated with DR in T2DM, including well-controlled individuals. These findings suggest AlbF may reflect glycaemic aspects not captured by HbA1c. Given the cross-sectional design, results should be interpreted as associations, not prediction or causality.
Evaluation of large language models for carbohydrate counting in type 1 diabetes mellitus: a comparative study with patient estimations.
Soyer AK, Akarsu GÇ, Yelli BD … +5 more , Tural Balsak BÖ, Özdemir D, Topaloğlu O, Ersoy R, Çakır B
Diabetes Res Clin Pract · 2026 Jun · PMID 42044810 · Publisher ↗
AIMS: To evaluate large language models (LLMs) accuracy in carbohydrate (CHO) counting (CC) and compare their performance with estimations by patients with type-1 diabetes mellitus (T1DM). METHODS: This cross-sectional s...
AIMS: To evaluate large language models (LLMs) accuracy in carbohydrate (CHO) counting (CC) and compare their performance with estimations by patients with type-1 diabetes mellitus (T1DM). METHODS: This cross-sectional study included 14 adults with T1DM with advanced CC training and > 70% accuracy on the AdultCarbQuiz. Eighteen main meals and four snacks were prepared by dietitians using standardized descriptions and two-angle photographs. Dietitian-determined values served as the reference. CHO estimations by patients and LLMs (ChatGPT-5.2, Gemini-3 Pro, and Claude Sonnet-4.5) were compared. LLM performance was evaluated in two-stages: image-only (stage-1) and image-plus-detailed-description (stage-2) inputs. Performance was assessed using mean absolute error (MAE), mean absolute percentage error (MAPE), counting accuracy (CA; ≤10 g), Wilcoxon signed-rank test, and Bland-Altman analysis. RESULTS: Patients showed MAE 8.31 g, MAPE 13.82%, and CA 73.74%. In Stage-1, Gemini had the lowest MAE (6.55 g), and MAPE (12.54%), while Claude achieved the highest CA (81.8%). In Stage-2, Gemini outperformed patients (p < 0.001) with MAE 2.14 g, MAPE 3.21%, CA 100%, and mean bias - 1.05 g. Other model-stage combinations showed performance comparable to patients. CONCLUSION: LLMs, particularly Gemini-3 Pro, may support CC when detailed inputs are provided; however, findings should be interpreted cautiously given the small, highly selected sample.
Efficacy and safety of anagliptin added to metformin and empagliflozin 25 mg in patients with type 2 diabetes: a 24-week randomized, double-blind, placebo-controlled phase 3 trial with 28-week open-label extension.
Moon JS, Han KA, Yu JM … +4 more , Won JC, Kang JG, Park S, Park CY
Diabetes Res Clin Pract · 2026 Jun · PMID 42036072 · Publisher ↗
AIMS: This study evaluated the efficacy and safety of anagliptin added to metformin and empagliflozin in patients with type 2 diabetes (T2DM) inadequately controlled on dual therapy. METHODS: In this multicenter, randomi...
AIMS: This study evaluated the efficacy and safety of anagliptin added to metformin and empagliflozin in patients with type 2 diabetes (T2DM) inadequately controlled on dual therapy. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 3 trial, patients with T2DM (HbA1c 7.0-11.0 %) on metformin (≥1000 mg/day) and empagliflozin (25 mg/day) were randomized 1:1 to anagliptin (100 mg twice daily) or placebo for 24 weeks, followed by a 28-week open-label extension. The primary endpoint was HbA1c change from baseline to week 24. RESULTS: Of 200 randomized patients, 197 were analyzed (baseline HbA1c 7.76 %). At week 24, the least-squares mean HbA1c change was -0.83 % with anagliptin versus -0.03 % with placebo (difference -0.80 %; 95 % CI - 0.95 to - 0.64; P < 0.0001). The least-squares mean change in HOMA-β was + 10.45 versus -6.02 with placebo (between-group difference 16.46; P = 0.0003). Adverse events were similar between groups, with no severe hypoglycemia or deaths. CONCLUSIONS: In this first placebo-controlled trial evaluating DPP-4 inhibitor addition to maximally dosed empagliflozin (25 mg) plus metformin, anagliptin significantly improved glycemic control and β-cell function with a favorable safety profile, supporting this triple combination as an effective intensification strategy.
Effects of time-restricted eating on glycemic control and variability in individuals with overweight/obesity and prediabetes: A secondary analysis of the RESET randomized controlled trial.
Kloura C, Jensen MM, Ekblond TS … +6 more , Pedersen HE, Raben A, Clemmensen KKB, Færch K, Blond MB, Quist JS
Diabetes Res Clin Pract · 2026 Jul · PMID 42025926 · Publisher ↗
AIM: The aim of this exploratory analysis was to investigate effects of time-restricted eating (TRE) on glycemic control and variability in adults with prediabetes. METHODS: This study utilized data from the Restricted E...
AIM: The aim of this exploratory analysis was to investigate effects of time-restricted eating (TRE) on glycemic control and variability in adults with prediabetes. METHODS: This study utilized data from the Restricted Eating Time (RESET) randomized controlled trial. A subset of 46 participants with prediabetes, allocated to either a 10-hour TRE intervention (n = 20) or the control group (n = 26), was analyzed. Changes in continuous glucose monitoring derived outcomes, fasting glucose and glycosylated hemoglobin (HbA1c), at 6 weeks and 3 months were assessed using a linear mixed-effects model. RESULTS: There were no between-group differences in fasting glucose or HbA1c after 6 weeks and 3 months. The 24-hour and daytime coefficient of variation were reduced within the TRE group after 6 weeks but not after 3 months. Nighttime average sensor glucose was lower in the TRE group compared with the control group after 6 weeks [-0.3 mmol/L (-0.6 to -0.1)], but this effect was not maintained after 3 months [-0.1 mmol/L (-0.4 to 0.2)]. CONCLUSION: TRE may have a small short-term beneficial effect on nighttime glucose levels in adults with prediabetes. Larger long-term TRE studies are warranted.
AIGC-driven virtual patients for diabetes: a systematic review.
Tang Y, Wen G, Wu H
Diabetes Res Clin Pract · 2026 Jun · PMID 42025925 · Publisher ↗
This systematic review (SR) examines the application of Artificial Intelligence-Generated Content (AIGC) in developing virtual patients (VPs) for diabetes management. Through structured analysis of current literature, th...
This systematic review (SR) examines the application of Artificial Intelligence-Generated Content (AIGC) in developing virtual patients (VPs) for diabetes management. Through structured analysis of current literature, the study demonstrates how AIGC methodologies address key clinical challenges: generative adversarial networks (GANs) create synthetic continuous glucose monitoring trajectories to overcome data scarcity; reinforcement learning (RL) optimizes personalized insulin regimens through simulated treatment responses; and multimodal fusion techniques generate detailed models for diabetic complications. These approaches demonstrate technical feasibility in retrospective analyses and experimental settings for medical education and clinical decision support. However, their translation to clinical practice awaits rigorous prospective validation with diabetes-specific endpoints. However, validation remains primarily retrospective, with limited prospective trials reporting diabetes-specific endpoints like time-in-range and hypoglycemia metrics. Critical implementation barriers include data privacy concerns, model generalizability across diabetes subtypes, and clinical workflow integration. An empirical mapping of included studies onto a three-dimensional maturity framework reveals that while 92% of studies achieve technical validation, none demonstrate implementation maturity and only one has prospective evidence of clinical efficacy. Future progress hinges on interdisciplinary collaboration to develop robust validation frameworks aligned with regulatory standards and to proactively mitigate algorithmic biases, thereby bridging the gap between technical innovation and dependable clinical application.
Continuous glucose monitoring for cystic fibrosis-related diabetes: impact on quality of life and glycaemic control.
Martini R, Samm DA, Routley A … +5 more , Gagliardi L, Chapman S, Hopkins E, Umapathysivam M, Morton J
Diabetes Res Clin Pract · 2026 Jun · PMID 42019581 · Publisher ↗
BACKGROUND/AIMS: Data for the use of continuous glucose monitoring (CGM) in cystic fibrosis related diabetes (CFRD) is lacking. The aim of this study is to establish efficacy and safety of CGM in CFRD to improve glycemic...
BACKGROUND/AIMS: Data for the use of continuous glucose monitoring (CGM) in cystic fibrosis related diabetes (CFRD) is lacking. The aim of this study is to establish efficacy and safety of CGM in CFRD to improve glycemic control and quality of life. METHODS: A prospective single-arm trial of 3 months CGM (Libre2®) in insulin requiring CFRD. All outcomes were assessed at baseline, completion of intervention and 3 months post completion. Glycemic control was assessed by glycated haemoglobin (HbA1c) and CGM metrics. QOL assessed by Problem Areas in Diabetes (PAID). RESULTS: 19 subjects were recruited. Median baseline HbA1c was 8.7% (72 mmol/mol) (IQR:8-10.6%, 64-92 mmol/mol), decreasing to 7.8% (62 mmol/mol) (IQR:7.3-8.3%, 56-67 mmol/mol), (p = 0.018) at completion of intervention, and remained lower than baseline at 8.0% (64 mmol/mol) (IQR: 7.0-9.0%, 53-75 mmol/mol) at 3 months post study intervention. Median baseline PAID score was 29.0 (IQR:16.0-48.5), decreasing to 16.0 (IQR: 11.0-22.0) (p = 0.02) at completion of intervention. At 3 months post completion median increased to 19.0 (IQR 11.5-23.0). There was no increase in time spent <3.0 mmol/L before and after sensor use (0.0% vs 0.3% p = 0.50). CONCLUSION: CGM use in CFRD improved QOL and glycaemic control without increases in hypoglycaemia.
The association between adverse childhood experiences (ACEs) and gestational diabetes mellitus (GDM): A systematic review and meta-analysis.
Fadhilah SN, Burton S, Wilson CA … +1 more , Benton M
Diabetes Res Clin Pract · 2026 Jun · PMID 42013918 · Publisher ↗
Gestational diabetes mellitus (GDM) has consequences for maternal and offspring health. Adverse childhood experiences (ACEs) contribute to GDM risk, but findings have been inconsistent. We synthesised evidence using a sy...
Gestational diabetes mellitus (GDM) has consequences for maternal and offspring health. Adverse childhood experiences (ACEs) contribute to GDM risk, but findings have been inconsistent. We synthesised evidence using a systematic review and meta-analysis of observational studies on ACEs before age 18 and GDM, including dose-response effects. Nine databases were searched from inception to 30 May 2025 based on a PROSPERO-registered protocol (CRD420251035754). Studies without extractable estimates or assessing diabetes not restricted to gestational onset were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-E. Random-effects models pooled adjusted odds ratios (aORs), with dose-response analyses using the Greenland-Longnecker method. Thirteen studies met eligibility criteria, 11 contributed to meta-analysis (n = 326,797). ACE exposure was associated with higher odds of GDM (aOR 1.15, 95% CI 1.12-1.18; I = 0%). A cumulative dose-response effect was observed, with each additional ACE increasing GDM odds (aOR 1.13, 95% CI 1.08-1.19). This study extends prior work by incorporating dose-response modelling, updated pooled estimates from recent cohorts, a pregnancy-focused risk window, and consideration of mediating and moderating pathways. Overall, ACEs are associated with increased risk of GDM, supporting a life-course approach to maternity care.
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