Journal of Diabetes Investigation最新文献

{"title":"Methodological considerations in interpreting serum galectin-3 as a predictor of incident type 2 diabetes.","authors":"Lingyan Chen, Dandan Weng","doi":"10.1111/jdi.70469","DOIUrl":"10.1111/jdi.70469","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206294","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":"Association between low-carbohydrate diet scores and macrovascular events or all-cause mortality in adults with type 1 diabetes in Japan.","authors":"Junko Sato, Tomoya Mita, Takuya Negami, Shohei Fujikawa, Haruki Nagashima, Eri Takagi, Shuhei Aoyama, Emi Otani, Yuya Nishida, Fuki Ikeda, Katsumi Aso, Hirotaka Watada","doi":"10.1111/jdi.70468","DOIUrl":"10.1111/jdi.70468","url":null,"abstract":"<p><strong>Aims/introduction: </strong>The effects of lifestyle factors on macrovascular events or all-cause mortality remain unclear in type 1 diabetes. We examined the associations of diet, physical activity, and sleep with these outcomes among adults with type 1 diabetes living in Japan.</p><p><strong>Materials and methods: </strong>This multicenter prospective cohort included 352 adults with type 1 diabetes from the Juntendo-Aso Type 1 Diabetes cohort. Lifestyle factors were assessed by questionnaire. Dietary intake was evaluated using a brief-type self-administered diet history questionnaire, from which Total, Plant, and Animal low-carbohydrate diet scores were calculated. The primary composite outcome was the first occurrence of ischemic heart disease, cerebrovascular disease, peripheral artery disease, or all-cause mortality. Associations were analyzed using Cox proportional hazards models.</p><p><strong>Results: </strong>Mean age was 51.4 ± 15.1 years, mean HbA1c was 7.9 ± 1.1%, and carbohydrate accounted for 49.3% of energy intake. During follow-up, 35 participants experienced the primary composite outcome. In multivariable Cox models, the Total LCDS (HR, 0.90; 95% CI: 0.82-0.98; P = 0.012), Plant LCDS (HR, 0.85; 95% CI: 0.76-0.94; P = 0.003), and Animal LCDS (HR, 0.93; 95% CI: 0.87-0.996; P = 0.037) were inversely associated with the outcome.</p><p><strong>Conclusions: </strong>Among adults with type 1 diabetes living in Japan, low-carbohydrate dietary patterns, particularly the Plant low-carbohydrate diet score, were inversely associated with macrovascular events or all-cause mortality.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190311","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":"Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.","authors":"Sayumi Kanie, Koki Nishida, Yusuke Seino, Shihomi Hidaka, Shinji Ueno, Hiroaki Sumioki, Eisuke Tomatsu, Takuya Haraguchi, Naoya Murao, Haruki Fujisawa, Takeshi Takayanagi, Yoshihisa Sugimura, Yoshitaka Hayashi, Atsushi Suzuki","doi":"10.1111/jdi.70466","DOIUrl":"10.1111/jdi.70466","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Glucagon is a key regulator of fasting glucose homeostasis, but the contribution of adrenal hormones during prolonged fasting remains unclear. We investigated the complementary roles of glucagon and adrenal hormones in hepatic glucose metabolism during prolonged fasting.</p><p><strong>Materials and methods: </strong>Male proglucagon-deficient (GCGKO) mice and adrenalectomized (ADX) mice were studied after a 36-h fast. Metabolic parameters, hepatic glycogen and lipid contents, gene expression, and liver metabolomic profiles were analyzed.</p><p><strong>Results: </strong>GCGKO mice exhibited markedly elevated plasma corticosterone levels and only mildly reduced blood glucose levels despite preserved hepatic glycogen stores after a 36-h fast. Hepatic triglyceride and free fatty acid contents were significantly lower in GCGKO mice. Fasting increased the expression of genes involved in amino acid metabolism and the urea cycle in both control and GCGKO mice, but the magnitude of the response was attenuated in GCGKO mice. Hepatic amino acid levels were broadly reduced in control mice but largely preserved in GCGKO mice. In contrast, adrenalectomy in GCGKO mice resulted in severe hypoglycemia accompanied by reduced adipose tissue lipolysis and impaired hormone-sensitive lipase phosphorylation. Adrenalectomy had minimal effects on blood glucose and hepatic metabolic responses in control mice.</p><p><strong>Conclusions: </strong>Glucagon-dependent glycogen utilization, adrenal hormone-dependent adipose lipolysis, and cooperative regulation of hepatic amino acid metabolism by glucagon and adrenal hormones contribute to the maintenance of blood glucose during prolonged fasting. Adrenal hormones provide an important compensatory mechanism that preserves glucose homeostasis when glucagon signaling is impaired.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190194","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":"Hepatic steatosis and postprandial hyperglucagonemia in early type 2 diabetes: Revisiting the liver-α-cell axis.","authors":"Yu-Ning Kuo, Jun-Sing Wang","doi":"10.1111/jdi.70471","DOIUrl":"10.1111/jdi.70471","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190425","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":"Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity.","authors":"Daiki Matsubara, Yumie Takeshita, Masahiro Mori, Yujiro Nakano, Kenichi Harada, Noboru Takata, Kengo Hayashi, Hideki Moriyama, Noriyuki Inaki, Masao Honda, Taro Yamashita, Toshinari Takamura","doi":"10.1111/jdi.70465","DOIUrl":"10.1111/jdi.70465","url":null,"abstract":"<p><strong>Aims: </strong>Weight loss by laparoscopic sleeve gastrectomy (LSG) compared to medical weight loss (low-calorie diet: LCD) ameliorates diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate changes in liver pathology 1-year after LSG and their associations with metabolic factors in Japanese participants with severe obesity.</p><p><strong>Materials and methods: </strong>We recruited 27 Japanese participants with severe obesity (BMI > 35 kg/m²) and metabolic disorders who showed inadequate weight loss after at least 6 months of medical treatment. LSG was performed after 4 weeks of LCD. Liver biopsy samples were obtained intraoperatively and at 1-year after surgery. The primary endpoint was the change in liver histopathological scores.</p><p><strong>Results: </strong>LSG significantly reduced histological scores in hepatic steatosis, hepatocellular ballooning, lobular inflammation, and hepatic fibrosis, together with fasting plasma glucose, hemoglobin A1c, body weight, body mass index, and liver enzymes. Reduction in steatosis was associated with a reduction in glycemic parameters and γ-glutamyl transpeptidase. Reduction in lobular inflammation was associated with reductions in liver enzyme levels and hemoglobin A1c. Changes in hepatic fibrosis were not associated with metabolic or biochemical changes but were related to baseline fibrosis severity and the presence of diabetes. Unexpectedly, weight reduction significantly lowered platelet counts and elevated the fibrosis-4 index.</p><p><strong>Conclusion: </strong>LSG improves liver histopathology of MASLD in Japanese participants with severe obesity. The comorbidity of diabetes was associated with attenuated improvement in liver fibrosis after LSG, suggesting that glycemic status and diabetes-related factors may be key modifiers of fibrosis reversibility in MASLD.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134427","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":"The cholesterol, high-density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new-onset cardiovascular-liver-metabolic multimorbidity: A prospective cohort study.","authors":"Zhonghua Sun, Aikeliyaer Ainiwaer, Yameng Xu, Ge Zhang, Xiangyu Sun, Xinliang Peng, Yuanhui Dai, Kaisaierjiang Kadier","doi":"10.1111/jdi.70462","DOIUrl":"10.1111/jdi.70462","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-liver-metabolic multimorbidity (CLMM), defined as the co-occurrence of at least two of cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, is an increasing health burden. We evaluated the cholesterol, high-density lipoprotein, and glucose (CHG) index and its obesity- and inflammation-derived variants for predicting incident CLMM.</p><p><strong>Methods: </strong>This prospective cohort included 6,534 adults aged ≥45 years from the China Health and Retirement Longitudinal Study. CHG, eight obesity-derived indices, and CHG-CRP were assessed, with the triglyceride-glucose index and TG/HDL-C ratio as comparators. Associations with incident CLMM were evaluated using logistic regression, restricted cubic splines, and threshold analysis. Predictive performance was compared using receiver operating characteristic analysis, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI), with additional joint-effect, interaction, subgroup, and sensitivity analyses.</p><p><strong>Results: </strong>At the 2015 follow-up, 406 participants (6.2%) met the criteria for CLMM. Higher CHG was linearly associated with incident CLMM (highest vs lowest quartile: OR 1.64, 95% confidence interval [CI] 1.22-2.22). Obesity-derived variants showed stronger associations, particularly CHG-BMI (OR 3.13, 95% CI 2.21-4.43), which also had the highest discrimination (AUC 0.643, 95% CI 0.616-0.669) and continuous NRI (34.08%). Participants with both high CHG and high BMI had the greatest CLMM risk (OR 2.59, 95% CI 1.94-3.51). Results were robust in sensitivity analyses.</p><p><strong>Conclusions: </strong>The CHG index and its obesity-derived variants, particularly CHG-BMI, are accessible and inexpensive candidate metabolic markers for predicting new-onset CLMM. CHG-BMI showed the highest apparent discrimination among the evaluated indices, although its AUC was modest. External population validation is needed.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134417","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":"A study of changes in insulin requirements related to the menstrual cycle in Japanese women with type 1 diabetes using the advanced hybrid closed-loop system.","authors":"Eri Takagi, Hideyoshi Kaga, Ryoki Mori, Shohei Fujikawa, Haruki Nagashima, Toshiki Kogai, Mami Koshibu, Junko Sato, Yuya Nishida, Fuki Ikeda, Yoshifumi Tamura, Hirotaka Watada","doi":"10.1111/jdi.70463","DOIUrl":"10.1111/jdi.70463","url":null,"abstract":"<p><strong>Aims/introduction: </strong>In type 1 diabetes (T1D), insulin requirements and glycemic control may vary across the menstrual cycle. We examined phase-related differences in insulin requirements, glycemic metrics, and recorded carbohydrate amounts in women using an advanced hybrid closed-loop (AHCL) system and their associations with menstrual symptoms and premenstrual dysphoric disorder (PMDD) screening status.</p><p><strong>Materials and methods: </strong>Fifteen premenopausal women with T1D using the MiniMed 780G without hormonal therapy were analyzed. Cycles with ≥2 eligible days (SmartGuard ≥70%) in both early follicular (d1-7) and late-luteal (d-7 to -1) phases were included. Phase differences were assessed using linear mixed-effects models. Associations between phase-related changes and menstrual symptom scores and PMDD screening status were evaluated using Spearman correlation and the Mann-Whitney U test, respectively.</p><p><strong>Results: </strong>Eighty cycles were analyzed. Compared with the early follicular phase, the late-luteal phase showed a higher total daily insulin dose (49.2 ± 3.7 vs 45.1 ± 3.7 U/day), basal insulin dose, total bolus insulin, and recorded carbohydrate amount (197.9 ± 18.2 vs 186.1 ± 18.2 g/day), with lower Time in Range (70.0 ± 3.2% vs 72.9 ± 3.2%) and higher Time above Range (TAR). Most phase-related differences persisted after adjustment for recorded carbohydrate amount. No clear associations between menstrual symptom scores or PMDD screening status and phase-related changes were detected.</p><p><strong>Conclusion: </strong>During AHCL therapy, insulin requirements increased and glycemic control modestly worsened in the late-luteal phase. No clear associations between phase-related metabolic changes and menstrual symptom scores or PMDD screening status were detected in this small cohort.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134401","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":"LGR6 couples maresin 1 signaling to glycolytic flux and protein lactylation for the rescue of diabetic cardiomyopathy.","authors":"Bin Feng, Chao Chen, Lin Chen, Yuqiong Chen, Wenjun Mao, Peiran Yu, Hao Yu, Bimin Shi, Nannan Zhang","doi":"10.1111/jdi.70464","DOIUrl":"10.1111/jdi.70464","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DbCM) is driven by metabolic inflexibility and impaired mitochondrial clearance. While the pro-resolving lipid mediator Maresin 1 (MaR1) shows therapeutic promise, its capacity to correct the underlying metabolic-epigenetic disturbances in DbCM remains undefined.</p><p><strong>Materials: </strong>Db/db mice and palmitic acid (PA)-exposed H9c2 cardiomyocytes were treated with MaR1. Cardiac function and structure were assessed by echocardiography and histological analysis. Myocardial oxidative stress, inflammation, and key molecular pathways were evaluated via immunoblotting, qPCR, immunohistochemistry, and transmission electron microscopy. The role of the putative receptor LGR6 was investigated using siRNA-mediated knockdown.</p><p><strong>Results: </strong>MaR1 improved cardiac diastolic function, attenuated pathological hypertrophy and interstitial fibrosis, and reduced oxidative stress and inflammatory markers in db/db mice. Mechanistically, MaR1 activated AMPK signaling, restoring the expression of crucial enzymes for both fatty acid oxidation (CPT1B) and glycolysis (PFK-1, HK2). This metabolic reprogramming elevated intracellular lactate, which in turn replenished the deficient global protein lysine lactylation (Kla). Concurrently, MaR1 reactivated the PINK1/Parkin pathway, restoring mitophagy-associated signaling. In vitro, exogenous lactate supplementation recapitulated these effects. Importantly, LGR6 silencing abrogated all MaR1-induced benefits, including glycolytic activation, lactylation rescue, and mitophagic recovery.</p><p><strong>Conclusion: </strong>MaR1 protects against DbCM by signaling through LGR6 to restore metabolic flexibility, thereby fueling a lactate-dependent lactylation program that is critically associated with the reactivation of mitochondrial quality control via mitophagy. This study unveils a critical metabolic-epigenetic axis as a novel therapeutic target.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126428","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":"Fasting proinsulin as a predictor of future glucose tolerance deterioration in Japanese adults.","authors":"Nobuhiro Kajihara, Tomonori Tsuyama, Kazuki Fukuda, Ai Maekawa, Eiichi Araki, Naoto Kubota, Kazuya Yamagata","doi":"10.1111/jdi.70461","DOIUrl":"10.1111/jdi.70461","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Proinsulin is associated with β-cell stress and has been linked to subsequent deterioration in glucose metabolism in Western populations, but its predictive value in Asian populations remains unclear. We investigated whether proinsulin is associated with future glucose tolerance deterioration in community-dwelling Japanese adults.</p><p><strong>Materials and methods: </strong>Of 160 individuals who underwent a 75-g oral glucose tolerance test (OGTT) in 2020-2021, 88 completed a follow-up OGTT in 2024-2025. Fasting proinsulin concentrations were measured using stored baseline serum samples from 84 participants. Associations with glucose tolerance deterioration were examined using Firth's penalized logistic regression, and discriminatory performance was evaluated using receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>During the 4-year follow-up, glucose tolerance deteriorated in 16 participants. Fasting proinsulin concentrations were higher in progressors than in non-progressors (5.8 vs. 3.6 pmol/L; P = 0.009). Each 1-standard deviation increase in fasting proinsulin was associated with glucose tolerance deterioration (odds ratio 2.11, 95% confidence interval 1.31-3.72; P = 0.002). In exploratory ROC analysis, the area under the curve was 0.710, and a cutoff of 5.1 pmol/L yielded 68.8% sensitivity and 83.8% specificity. Participants with elevated fasting proinsulin (≥ 5.1 pmol/L) and a low disposition index (≤ 1.27) had the highest odds of deterioration.</p><p><strong>Conclusions: </strong>Fasting proinsulin may help identify Japanese adults at risk of future glucose tolerance deterioration, particularly when combined with indices of β-cell compensation.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126419","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":"Renal glycogen handling in diabetes: A narrative review of diabetic kidney disease pathogenesis.","authors":"Deenadhayalan Ashok, Poornima Ajay Manjrekar, Bhushan Chandrahasa Shetty, Sujina Simon Sailet","doi":"10.1111/jdi.70448","DOIUrl":"https://doi.org/10.1111/jdi.70448","url":null,"abstract":"<p><p>Kidney disease is a major microvascular complication of diabetes, affecting approximately 40% of individuals with diabetes, and is a leading cause of end-stage renal disease. Besides the functional consequences of hyperglycemia; hemodynamic alterations are well understood. Activation of the sorbitol and hexosamine pathways, formation of advanced glycated products, and prevailing oxidative stress in the background of diabetic hyperglycemia are determinants of diabetic kidney disease (DKD) and its progression. The contribution of ectopic glycogen deposition remains unexplored. Glycogen metabolism in the kidneys is well regulated under physiological conditions, yet chronic hyperglycemia disrupts this balance across podocytes, tubular cells, and the glomerulus. Abnormal glycogen buildup has been observed in experimental diabetes models and human biopsy samples. GSK3β inactivation and mTORC1 upregulation emerge as central regulators. Metformin and SGLT2 inhibitors alter renal glycogen flow via AMPK-dependent pathways, a potential avenue for therapeutic exploration. The significance of observational studies needs to be further explored for the potential involvement of glycogen buildup in the pathogenesis of DKD. This narrative review aims to provide a comprehensive understanding of glycogen metabolism, examine the dysregulation of key enzymes and signaling pathways, collate available evidence from animal and clinical studies and propose hypothesis that glycogen accumulation may have an additive role in the progression of DKD.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101718","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}