Acta Diabetologica最新文献

{"title":"Diabetes, prediabetes, and mild cognitive impairment among older adults: the Hitachi Health Study II","authors":"Ami Fukunaga,&nbsp;Aoi Ito,&nbsp;Yosuke Inoue,&nbsp;Hitomi Inada,&nbsp;Tohru Nakagawa,&nbsp;Shuichiro Yamamoto,&nbsp;Maki Konishi,&nbsp;Tetsuya Mizoue","doi":"10.1007/s00592-026-02720-6","DOIUrl":"10.1007/s00592-026-02720-6","url":null,"abstract":"<div><h3>Aim</h3><p>We examined associations of diabetes, prediabetes, and glycemic markers with mild cognitive impairment (MCI) in older adults, and whether these associations are modified by treatment status, diabetes duration, and glycemic control.</p><h3>Methods</h3><p>We used data from 2486 adults (mean age: 65 years) undergoing health check-ups and cognitive screening. Prediabetes and diabetes were defined by fasting plasma glucose (FPG), HbA1c, or history/medication use. Diabetes was divided into screen-detected and treated cases. Cognitive function was tested using a computerized test battery evaluating immediate memory, temporal orientation, delayed recall, and three-dimensional visual-spatial perception. Participants scoring ≤ 13 (range, 0–15) were considered to have MCI.</p><h3>Results</h3><p>Overall, 251 participants (10.1%) were classified with MCI. Compared with normoglycemia, odds ratios (95% CIs) were 1.45 (0.90, 2.33) for prediabetes and 1.67 (0.99, 2.81) for diabetes. When stratified by treatment status, the odds ratios were larger in treated diabetes than in screen-detected diabetes (1.77 [1.03, 3.06] vs. 1.48 [0.77, 2.84]). Larger odds ratios were also found among those with diabetes duration ≥ 10 years (2.26, 95% CI: 1.27, 4.02) and HbA1c ≥ 7% (1.90, 95% CI: 1.00, 3.60). Diabetes was associated with lower scores in temporal orientation and visual-spatial perception. Among participants without diabetes, higher FPG was associated with higher odds of MCI; the odds ratio for FPG 110–125 vs. &lt;100 mg/dL was 1.85 (95% CI: 1.18, 2.89).</p><h3>Conclusion</h3><p>Older adults with diabetes, particularly those with treated, longstanding, or uncontrolled diabetes, had a higher prevalence of MCI. Among those without diabetes, higher FPG was associated with MCI.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1435 - 1446"},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-026-02720-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metrics and insulin variations in women with type 1 diabetes on automated insulin delivery system during strict peripartum period","authors":"Raffaella Fresa,&nbsp;Angela Napoli,&nbsp;Olimpia Bitterman","doi":"10.1007/s00592-026-02733-1","DOIUrl":"10.1007/s00592-026-02733-1","url":null,"abstract":"<div><h3>Introduction</h3><p>the use of Automated Insulin Delivery (AID) systems has increased in pregnant women with type 1 diabetes (DM1). To date, little data exist regarding glucose control and insulin modifications with AID in automode during delivery and in the postpartum period.</p><h3>Methods</h3><p>we retrospectively evaluated pregnancy-specific metrics and insulin variations in a short peripartum period in 14 DM1 users of the MiniMed™780G pump in closed loop mode from pregestational care to the postpartum period.</p><h3>Results</h3><p>glycemic control during labour and delivery was optimal, with Time In Range 63–140 mg/dl (pTIR) did not significantly change, remaining nearly the same from 48 h before to 48 after the time of birth (85%). Variations in the Total insulin daily dose (TDD) were mainly influenced by manual boluses rather than the autobasal insulin in all examined periods. Auto basal insulin + autocorrection boluses reduced by 17.5% immediately after delivery and by 31% in the early postpartum period (14 days).</p><h3>Conclusions</h3><p>this is the first study to report on insulin variations with an AID system in automode during the strict peripartum period, before and after the time of birth. pTIR did not significantly change, remaining nearly the same from 48 h before to 48 after the time of birth, despite the dramatic variations in insulin requirements, with unexpected little variation in autobasal insulin. It is possible that, for patients with very good glycemic control using Minimed^TM780G, the manual basal rate needs to be reduced less than the usual 50% after delivery, if switching to manual mode for any reason. Further research is needed to develop a protocol for glucose management in women with AID systems during and after delivery.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 9","pages":"1537 - 1544"},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Super learner model for predicting carotid plaque regression in type 2 diabetes on PCSK9 inhibitors","authors":"Jingyao Chen,&nbsp;Qinglong Yang,&nbsp;Gaoming Hou,&nbsp;Jianqiao Bi,&nbsp;Qi Xu,&nbsp;Haiting Guo,&nbsp;Jia Sun","doi":"10.1007/s00592-026-02729-x","DOIUrl":"10.1007/s00592-026-02729-x","url":null,"abstract":"<div><h3>Objectives</h3><p>Evidence regarding the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on carotid plaque regression in patients with type 2 diabetes mellitus (T2DM) and subclinical atherosclerosis remains limited; therefore, this study aimed to develop and validate a machine learning-based model for predicting carotid plaque regression in this population.</p><h3>Methods</h3><p>This retrospective study included a development cohort of 204 patients with T2DM and subclinical atherosclerosis receiving combined statin and evolocumab therapy, with external validation performed in an independent cohort. The primary outcome was the change in mean carotid plaque thickness. Thirteen predictors were selected using the Boruta algorithm to construct a Super Learner model, which was validated through repeated five-fold cross-validation. Model interpretability was assessed using SHapley Additive exPlanations analysis.</p><h3>Results</h3><p>After 24 weeks of treatment, carotid plaque regression was observed in 52.9% of patients. The model demonstrated strong discriminatory performance in the internal validation set (area under the curve [AUC] = 0.958; sensitivity = 0.881; specificity = 0.908) and moderate performance in the external validation cohort (AUC = 0.755; sensitivity = 0.875; specificity = 0.560). Low-density lipoprotein cholesterol, total cholesterol, high-sensitivity C-reactive protein, high-density lipoprotein cholesterol, and alanine aminotransferase were identified as the most influential predictors.</p><h3>Conclusions</h3><p>This study demonstrates the feasibility of applying machine learning algorithms to predict responses to evolocumab in patients with T2DM and subclinical atherosclerosis. Machine learning may support individualized risk stratification by identifying individuals most likely to benefit from therapy, thereby supporting personalized strategies for secondary cardiovascular disease prevention.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 9","pages":"1515 - 1523"},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maturity onset diabetes of the young in pregnancy: management, treatment and neonatal outcomes-a systematic review.","authors":"Alessandra Romandini, Michela Vergani, Arianna Pani, Federico Bertuzzi, Basilio Pintaudi","doi":"10.1007/s00592-026-02726-0","DOIUrl":"https://doi.org/10.1007/s00592-026-02726-0","url":null,"abstract":"<p><p>Maturity Onset Diabetes of the Young (MODY) is a type of genetically inherited diabetes. As it generally arises in early adulthood, it can affect pregnant women with significant neonatal outcomes. Our study aimed to conduct a systematic review on pregnancy management and outcomes of all subtypes of MODY, browsing the Cochrane, EMBASE and PubMed databases to find clinical studies on the topic. They were last searched on June 29, 2025. The inclusion criteria for our review were: published articles, available in their full-text version, about MODY, reporting data about its management during pregnancy and neonatal outcomes, in English language, specifying therapeutic approaches used. The exclusion criteria were: study designs reported below, written in other languages, not present in above mentioned databases. The risk of bias was assessed through the ROBIS tool. Our systematic review analyzed data on 1408 live births of 1183 pregnant women, and found specific guidelines for the management of pregnant women affected with GCK-MODY and HNF1A-MODY, but none on rarer subtypes. Thus, indications on pregnancy management and outcomes of rarer MODYs were identified through an additional literature review, and its findings were summarized in Table 1. Our systematic review was limited by the lack of data on rarer subtypes of MODY and the specific keywords and databases selected. However, our work lays an important step in the direction of much-needed clinical data and recommendations in treating rare MODY subtypes during pregnancy, towards healthy offspring delivery and growth. A further literature review was carried out to identify any data on other subtypes of MODY and their neonatal outcomes, and the findings were summarized in Table 1. No funding was needed to carry out the present systematic review. PROSPERO registration number: CRD420251062633.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic control and clinical outcomes in patients with diabetes and atrial fibrillation: a nationwide cohort study","authors":"Elis Kouki,&nbsp;Birgitta Salmela,&nbsp;Aapo Aro,&nbsp;Olli Halminen,&nbsp;Konsta Teppo,&nbsp;Leo Niskanen,&nbsp;Jari Haukka,&nbsp;Jukka Putaala,&nbsp;Miika Linna,&nbsp;Pirjo Mustonen,&nbsp;Juha Hartikainen,&nbsp;K. E. Juhani Airaksinen,&nbsp;Mika Lehto","doi":"10.1007/s00592-026-02725-1","DOIUrl":"10.1007/s00592-026-02725-1","url":null,"abstract":"<div><h3>Aims</h3><p>To evaluate the association of HbA1c level at the time of atrial fibrillation (AF) diagnosis with adverse outcomes (death, ischemic stroke (IS), myocardial infarction (MI), bleeding) in an unselected nationwide cohort of patients with AF and diabetes mellitus (DM).</p><h3>Methods</h3><p>The retrospective FinACAF registry study covered all patients with incident AF in Finland between 2010 and 2017. Outcomes were analyzed using HRs and sHRs (hazard ratios and subdistribution hazard ratios), with HbA1c modelled both categorically and continuously.</p><h3>Results</h3><p>Among 157 658 patients with incident AF, DM was present in 23% (n = 35 872). Baseline HbA1c was available in 49% (17 519) of DM patients. DM was associated with increased hazards of all evaluated outcomes. Elevated HbA1c in categorical analyses was associated with progressively increased adjusted HRs and sHRs, with highest ratios seen in HbA1c &gt; 63 mmol/mol for death (HR 1.56, 95% CI 1.45–1.68), IS (sHR 1.38 95% CI 1.20–1.59), and MI (sHR 1.70 95% CI 1.48–1.94), when compared to patients without DM. In continuous analyses, higher HbA1c levels were associated with increasing hazards for mortality, IS, and MI. Bleeding hazards remained stable across the HbA1c spectrum.</p><h3>Conclusions</h3><p>Higher baseline HbA1c levels were associated with progressively increased hazards of mortality, IS, and MI in patients with incident AF and DM.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1459 - 1468"},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-026-02725-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes of autologous cell therapy in patients with ischaemic diabetic foot ulcers and no-option chronic limb threatening ischaemia","authors":"Meloni Marco,&nbsp;Bellizzi Ermanno,&nbsp;Uccioli Luigi,&nbsp;Morosetti Daniele,&nbsp;Giurato Laura,&nbsp;Bonanni Federico Rolando,&nbsp;Ruotolo Valeria,&nbsp;Andreadi Aikaterini,&nbsp;Bellia Alfonso,&nbsp;Lauro Davide","doi":"10.1007/s00592-026-02721-5","DOIUrl":"10.1007/s00592-026-02721-5","url":null,"abstract":"<div><h3>Aim</h3><p>Patients with ischaemic diabetic foot ulcers (DFUs) and no-option chronic limb-threatening ischaemia (CLTI) are reported to have a high risk of major amputation and mortality. Peripheral blood mononuclear cell (PB-MNCs) therapy has emerged as a promising adjunctive strategy, but long-term data remain limited. The study aimed to evaluate the long-term outcomes of PB-MNC therapy in patients with DFUs and NO-CLTI.</p><h3>Methods</h3><p>This prospective, single-centre, observational, controlled study included patients with ischaemic DFUs and no-option CLTI enrolled between January 2017 and September 2023. No-option CLTI was defined by a technical failure of lower limb revascularization with the absence of any below-the-ankle vessel and/or indirect revascularization with TcPO₂ values &lt; 30 mmHg in the wound angiosome area. Patients were divided into two groups: those receiving PB-MNCs therapy plus standard of care (SoC) and those treated only with SOC based on conventional guidelines. PB-MNCs were administered by intramuscular injections along the anatomical area of the wound-related artery (2 or 3 cycles, 21–42 days apart). At 24 months of follow-up, outcomes assessed were healing, major amputation, and mortality. In the PB-MNC group, hospital readmission for recurrent CLTI requiring repeat revascularization was also recorded.</p><h3>Results</h3><p>Overall, 78 patients were included: 48 in the PB-MNCs group and 30 in the conventional therapy group. The mean age was 73.7 years, 84.6% were male, and most had type 2 diabetes (92.3%). At the baseline assessment, 71.8% of DFUs were infected, 83.3% were &gt; 5 cm², and 88.5% had gangrene. At 24 months, the PB-MNCs group showed a higher rate of healing (60.4 vs. 20%, <i>p</i> &lt; 0.0001), lower rate of major amputation (12.5 vs. 26.7%, <i>p</i> = 0.0004), and mortality (27.1 vs. 46.7%, <i>p</i> = 0.0002) than the control group. CLTI recurrence requiring readmission occurred in 3/48 (6.2%) among patients in the PB-MNC group.</p><h3>Conclusions</h3><p>In patients with ischaemic DFUs and NO-CLTI, adjunctive PB-MNCs therapy was associated with better long-term outcomes in comparison to conventional therapy.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1447 - 1457"},"PeriodicalIF":3.1,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-026-02721-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylketonuria and type 1 diabetes: a clinical and nutritional challenge in a young adult—a case report","authors":"Carmine Piccolo,&nbsp;Sara de Candia,&nbsp;Annalisa Natalicchio,&nbsp;Sergio Di Molfetta,&nbsp;Irene Caruso,&nbsp;Luigi Laviola,&nbsp;Francesco Giorgino,&nbsp;Gian Pio Sorice","doi":"10.1007/s00592-026-02685-6","DOIUrl":"10.1007/s00592-026-02685-6","url":null,"abstract":"<div><h3>Aims</h3><p>Phenylketonuria and type 1 diabetes are lifelong metabolic disorders requiring complex and potentially conflicting nutritional strategies. Their coexistence is rare, yet management may become particularly challenging during transition from pediatric to adult care. We describe the case of a young adult with phenylketonuria who developed type 1 diabetes.</p><h3>Methods</h3><p>A 27-year-old man with longstanding phenylketonuria was referred to an adult metabolic-diabetes center after the diagnosis of type 1 diabetes. Clinical, biochemical, nutritional, and continuous glucose monitoring data were reviewed. The intervention included structured therapeutic education, transition from fixed insulin doses to a dynamic regimen based on carbohydrate counting, and revision of medical nutrition therapy using phenylketonuria-adapted low-protein foods and sugar-free phenylalanine-free amino acid supplements.</p><h3>Results</h3><p>At diagnosis, HbA1c was 11.5%, with markedly reduced C-peptide levels and high titer anti-GAD antibodies. Initial diabetes management was associated with poor adherence to the phenylketonuria diet, increased intake of conventional protein sources, and elevated phenylalanine levels. After individualized insulin titration and nutritional intervention, HbA1c improved from 11.5% to 7.8%, phenylalanine levels decreased from 842 to 705 μmol/L, insulin requirement declined from 0.55 to 0.3 IU/kg/day, and continuous glucose monitoring showed improved glycemic control without increased hypoglycemia. The Glycemia Risk Index improved from high-risk Zone E to low-intermediate-risk Zone B.</p><h3>Conclusions</h3><p>This case highlights the need for personalized multidisciplinary care integrating continuous glucose monitoring, carbohydrate counting, and phenylketonuria specific nutrition to optimize both metabolic conditions.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1405 - 1409"},"PeriodicalIF":3.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-026-02685-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Therapeutic role of gut microbial metabolite indole propionic acid in a rat model of high-fat diet/Streptozotocin-Induced diabetes: enhancing glucose metabolism, antioxidant defense and PI3K/Akt/GLUT4 signaling pathway","authors":"Nayab Shuja,&nbsp;Imran Tarique,&nbsp;Sehrish Sohail,&nbsp;Iram Taalay","doi":"10.1007/s00592-026-02688-3","DOIUrl":"10.1007/s00592-026-02688-3","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1403 - 1403"},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HbA1c variability as an independent risk factor for diabetic retinopathy: results from a screening program","authors":"Maria Ida Maiorino,&nbsp;Carlo Gesualdo,&nbsp;Silvia Angelino,&nbsp;Settimio Rossi,&nbsp;Nicole Di Martino,&nbsp;Clemente Iodice,&nbsp;Miriam Longo,&nbsp;Lorenzo Scappaticcio,&nbsp;Giuseppe Bellastella,&nbsp;Francesca Simonelli,&nbsp;Katherine Esposito","doi":"10.1007/s00592-026-02711-7","DOIUrl":"10.1007/s00592-026-02711-7","url":null,"abstract":"<div><h3>Aims</h3><p>To investigate the independent association between long-term glycemic variability, measured as the coefficient of variation (CV) of HbA1c, and the presence of diabetic retinopathy (DR) in a cohort of adults with diabetes within a systematic eye screening program.</p><h3>Methods</h3><p>This study screened 379 adults with type 1 and type 2 diabetes. Long-term glycemic variability was calculated as the CV of serial HbA_1c measurements. DR was assessed via dilated fundus photography. The association between HbA_1c CV and DR was analyzed using multivariable logistic regression adjusting for confounders.</p><h3>Results</h3><p>DR incidence of 12.4%, mostly mild non-proliferative. The median HbA_1c CV was 7.0% (53 mmol/mol). In unadjusted bivariate analysis, the incidence of mild DR was higher in the low- glycemic variability group (CV &lt; 5%) compared to the high- glycemic variability group. However, the multivariable logistic regression analysis revealed that higher HbA_1c CV was independently associated with the presence of DR (β = 0.643, P = 0.042), alongside diabetes duration (P &lt; 0.001) and age (P &lt; 0.001).</p><h3>Conclusions</h3><p>In conclusion, in a cohort of individuals with both type 1 and type 2 diabetes and a low incidence of DR, long-term glycemic variability, estimated as HbA_1c CV, was independently associated with an increased risk of this complication.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 8","pages":"1395 - 1402"},"PeriodicalIF":3.1,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00592-026-02711-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Converging TCF7L2 and CDKAL1 pathways in the pathogenesis of type 2 diabetes mellitus","authors":"Meena S. Farman,&nbsp;Maryam I. Salman,&nbsp;Omar M. Hasan","doi":"10.1007/s00592-026-02719-z","DOIUrl":"10.1007/s00592-026-02719-z","url":null,"abstract":"<div><p>Type 2 diabetes mellitus develops when insulin resistance raises insulin demand and pancreatic beta cells fail to sustain insulin supply. Genome-wide association studies support a polygenic architecture and enrich for loci that affect beta cell stimulus secretion coupling and secretory stress responses. Polygenic risk scores summarize liability across many variants and guide genetic stratification in cohort studies. This review uses TCF7L2 and CDKAL1 as two mechanistically interpretable loci to connect inherited variation to measurable physiology. TCF7L2 risk alleles reduce incretin potentiation of insulin secretion after oral nutrient exposure, which blunts early postprandial insulin release. CDKAL1 risk alleles impair the ms2 modification of t6A37 at position 37 of tRNALys(UUU), which increases proinsulin mistranslation and raises endoplasmic reticulum stress in beta cells. These defects converge during repeated postprandial cycles that require rapid insulin synthesis and secretion. Reduced incretin signaling prolongs glycemic excursions and increases secretory workload, which intensifies folding stress when translation quality control is limited. The model predicts earlier postprandial dysglycemia under obesity or aging related insulin resistance and faster loss of beta cell reserve when both pathways constrain supply. The framework supports mechanistic phenotyping and pharmacogenetic testing within a broader polygenic risk setting.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"63 10","pages":"1669 - 1681"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}