Diabetology International最新文献

{"title":"Physiotherapist-guided, wearable-informed exercise improves 6-minute walk distance in patients with type 2 diabetes, including those with diabetic kidney disease: a prospective study.","authors":"Momo Takahashi, Yuma Tamura, Hajime Tamiya, Masato Terashima, Harunori Takahashi, Nobuyuki Banba, Yuki Nakatani, Naoyuki Otani, Asuka Ueno, Takanori Yasu, Yasuhiro Maejima","doi":"10.1007/s13340-026-00900-x","DOIUrl":"10.1007/s13340-026-00900-x","url":null,"abstract":"<p><strong>Background: </strong>Evidence for wearable-guided physiotherapy in diabetic kidney disease (DKD) is limited. This study evaluated the effects of physiotherapist-supervised exercise supported by wearable device feedback in patients with type 2 diabetes, including those with DKD.</p><p><strong>Methods: </strong>In this single-center, prospective study, 58 outpatients were allocated to an intervention group (IG) or non-intervention group (NIG). The per-protocol set included 45 participants completing six months (IG = 25, NIG = 20). IG wore a wrist-worn device and received monthly physiotherapist-led guidance; NIG received standard care. The primary endpoint was 6-min walk distance (6MWD); secondary outcomes included weight-bearing index (WBI), phase angle (PhA), HbA1c, and eGFR. Analyses used linear mixed-effects models adjusted for covariates.</p><p><strong>Results: </strong>IG improved 6MWD from 512.0 m to 551.0 m (+ 38.7 m), while NIG changed from 410.0 m to 407.0 m (- 3.7 m). The group × time interaction was significant (<i>p</i> < 0.001); adjusted between-group difference was + 42.4 m (95% CI: 20.3-64.5). IG showed greater reductions in HbA1c (- 0.89%, 95% CI: - 1.53 to - 0.25; <i>p</i> = 0.008) and improvements in WBI and PhA (<i>p</i> < 0.01). Changes in eGFR were not significant (0.65 mL/min/1.73m², 95% CI: -3.84 to 5.14; <i>p</i> = 0.78).</p><p><strong>Conclusions: </strong>Monthly physiotherapist-led exercise supported by wearable feedback improved functional capacity and glycemic control in patients with DKD. This pragmatic, scalable model may enhance outpatient rehabilitation strategies.</p><p><strong>Graphical abstract: </strong>Values represent adjusted between-group differences in change from baseline to six months, estimated using linear mixed-effects models with group, time, and group × time interaction, adjusted for age, baseline 6-min walk distance, HbA1c, eGFR, cardiovascular disease, and smoking status. Error ranges indicate 95% confidence intervals. Arrows indicate direction of change favoring the intervention group.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00900-x.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 3","pages":"45"},"PeriodicalIF":1.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthropometry-adjusted TyG indices improve insulin resistance estimation: an exploratory euglycemic-hyperinsulinemic clamp study in Japanese adults without diabetes.","authors":"Natsu Otowa-Suematsu, Tomoaki Nakamura, Hiroshi Miura, Tomoko Yamada, Marika Nishisaka, Hayato Fukumitsu, Yukari Katsura, Yasuko Morita, Shun-Ichiro Asahara, Kazuhiko Sakaguchi","doi":"10.1007/s13340-026-00883-9","DOIUrl":"10.1007/s13340-026-00883-9","url":null,"abstract":"<p><strong>Background: </strong>We evaluated the diagnostic performance of anthropometry-adjusted triglyceride-glucose (TyG)-derived indices for assessing insulin resistance (IR) in Japanese adults without diabetes, using the euglycemic-hyperinsulinemic clamp (EHC) as the reference standard.</p><p><strong>Methods: </strong>A total of 61 Japanese individuals without diabetes underwent insulin sensitivity assessment using the gold standard EHC. IR was defined as an insulin sensitivity index (ISI) below the 25th percentile. Surrogate IR indices, including Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the original TyG index, and anthropometry-adjusted TyG-derived indices (TyG-BMI, TyG-WC, TyG-WHtR), were calculated. Correlations between these indices and the ISI were evaluated using Spearman's rank correlation. Receiver operating characteristic (ROC) analysis and linear regression were used to compare diagnostic accuracy and predictive ability. Pairwise DeLong tests were used to assess differences in the area under the curve (AUC) values.</p><p><strong>Results: </strong>TyG-BMI and TyG-WHtR showed the stronger associations with ISI (ρ = - 0.544 and - 0.546, respectively) than both HOMA-IR and the original TyG index. TyG-BMI and TyG-WHtR had the highest AUCs (0.810 and 0.829, respectively) for identifying clamp-defined IR. The optimal cutoff value for HOMA-IR was approximately 2.5. The optimal cutoff for TyG-BMI was 203.7. Pairwise DeLong tests supported the higher diagnostic performance of selected anthropometry-adjusted TyG-derived indices compared with conventional markers.</p><p><strong>Conclusions: </strong>Anthropometry-adjusted TyG-derived indices, particularly TyG-BMI and TyG-WHtR, showed strong associations with IR as assessed by the gold standard EHC in Japanese adults without diabetes. These findings suggest that these indices may serve as practical surrogate markers for IR in settings where direct clamp measurements are not feasible.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00883-9.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"35"},"PeriodicalIF":1.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute onset of neovascular age-related macular degeneration after initiation of tirzepatide.","authors":"Kohzo Takebayashi, Yurina Iemura, Mototaka Yamauchi, Kenji Hara, Takafumi Tsuchiya, Shigeki Machida, Koshi Hashimoto","doi":"10.1007/s13340-026-00885-7","DOIUrl":"10.1007/s13340-026-00885-7","url":null,"abstract":"<p><p>Recent retrospective cohort studies showed that use of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) increased the incident risk of diabetic retinopathy and nonarteritic anterior ischemic optic neuropathy (NAION). Furthermore, it was recently reported that use of GLP-1RAs for more than 6 months increased the risk of neovascular age-related macular degeneration (nAMD) by about twofold, although the association between a gastric inhibitory polypeptide (GIP)/GLP-1 receptor dual agonist (GIP/GLP-1RA) and nAMD is not clearly established. We describe the case of a middle-aged male patient with type 2 diabetes without apparent diabetic retinopathy. Due to poor glycemic control, tirzepatide (a GIP/GLP-1RA) was started instead of sitagliptin (a dipeptidyl peptidase-4 inhibitor). After switching from sitagliptin to tirzepatide, glycemic control rapidly improved, but the patient felt haziness with distortion of the central part of the left eye. A diagnosis of neovascular age-related degeneration (nAMD) was made by ophthalmologists in our hospital. The basis for the possible association of tirzepatide administration with onset of nAMD is unknown. However, clinicians should pay attention to potential visual impairments after achieving acute glycemic control with incretin-related drugs, including tirzepatide.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"37"},"PeriodicalIF":1.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of a rapid-acting insulin bolus at the initiation of continuous insulin infusion therapy in patients with hyperglycemic crisis: a propensity score-matched analysis.","authors":"Yuichiro Iwamoto, Tomohiko Kimura, Takashi Itoh, Toshitomo Sugisaki, Kazunori Dan, Hideyuki Iwamoto, Yoshiro Fushimi, Junpei Sanada, Masashi Shimoda, Shuhei Nakanishi, Kohei Kaku, Hideaki Kaneto","doi":"10.1007/s13340-026-00892-8","DOIUrl":"https://doi.org/10.1007/s13340-026-00892-8","url":null,"abstract":"<p><strong>Background: </strong>The use of insulin bolus at the initiation of continuous intravenous insulin infusion (CII) in hyperglycemic emergencies remains controversial, with limited real-world data in patients with severe presentations. Although some guidelines discourage its routine use, there are many variations in clinical practice and its clinical benefit remains uncertain.</p><p><strong>Methods: </strong>We conducted a retrospective single-center study using propensity score matching to evaluate the impact of rapid bolus insulin administration at the start of CII in diabetic patients with hyperglycemic emergencies. Among 99 patients treated with CII between April 2010 and December 2024, 21 pairs of patients with and without bolus insulin were matched based on clinical and biochemical severity indicators. Clinical outcomes and glycemic control parameters were compared using Wilcoxon rank-sum and chi-square tests.</p><p><strong>Results: </strong>Rapid bolus insulin administration did not improve the length of hospital period, time to CII withdrawal, or glycemic control in the short and long term. However, the bolus group showed significantly higher insulin use during the treatment and greater fluctuations in serum potassium levels (Δpotassium: 1.2 (0.8-1.9) vs. 1.0 (0.4-1.3) mmol/L, <i>p</i> = 0.049). No significant differences were observed in rates of hypokalemia, mortality, or other adverse events.</p><p><strong>Conclusion: </strong>Rapid bolus insulin administration at the initiation of CII was not associated with the improvement of clinical outcomes or faster glycemic recovery. It was associated with the increase of insulin use and potassium variability. These findings suggest that a more conservative approach without an initial bolus of insulin is sufficient in managing hyperglycemic emergencies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00892-8.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"38"},"PeriodicalIF":1.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional category, physical frailty, and sarcopenia in older adults with diabetes mellitus: a cross-sectional study.","authors":"Takuya Omura, Taiki Sugimoto, Ayumi Sugie, Mariko Ban, Ayano Toda, Seiya Tanaka, Tomoyasu Kinoshita, Naoki Yamauchi, Makio Tanabashi, Yoshiharu Ohshima, Naoki Takashi, Shosuke Ohtera, Takahiro Kamihara","doi":"10.1007/s13340-026-00890-w","DOIUrl":"10.1007/s13340-026-00890-w","url":null,"abstract":"<p><strong>Aims: </strong>To describe how a three-level functional category (DAFS-8; lower categories indicating better function) overlaps with physical frailty and sarcopenia in older outpatients with diabetes, and to explore whether their combination provides clinically interpretable risk stratification for prioritizing care.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 122 outpatients aged ≥ 65 years. Physical frailty was defined by the revised Japanese Cardiovascular Health Study (J-CHS) phenotype, and sarcopenia/possible sarcopenia by the AWGS 2019 criteria. Discriminative performance was evaluated using receiver operating characteristic (ROC) analyses and rule-based performance metrics.</p><p><strong>Results: </strong>Prefrailty/frailty, sarcopenia, and possible sarcopenia were present in 70.5%, 23.8%, and 64.8% of participants, respectively. Sarcopenia was almost exclusively concentrated among those classified as prefrail or frail (96.6%). The intersection of prefrailty/frailty and functional category II/III captured 48.3% of sarcopenia cases. While frailty alone showed high sensitivity (96.6%) but limited specificity (37.6%), this intersection-based condition showed higher specificity (80.6%) and positive predictive value (43.8%). ROC analyses <i>showed a numerically higher AUC when functional category was added to frailty (0.733 vs. 0.671)</i>, <i>although the confidence intervals overlapped.</i></p><p><strong>Conclusions: </strong>Functional category and physical frailty capture complementary aspects of vulnerability. Sarcopenia in older adults with diabetes was not uniformly distributed across frailty states but was specifically concentrated within the prefrail-to-frail spectrum. Their overlap identifies subgroups where sarcopenia is disproportionately enriched, supporting a <i>potential</i> triage perspective for prioritizing interventions in routine outpatient care. These findings illustrate how multiple geriatric \"measuring sticks\" capture distinct but overlapping segments of this heterogeneous population.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"36"},"PeriodicalIF":1.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein 72 (HSP72) modulates glucagon secretion via JNK inhibition in pancreatic α-cells.","authors":"Takuro Watanabe, Tatsuya Kondo, Rintaro Yoshizumi, Nobukazu Miyakawa, Sayaka Kitano, Mary Ann Suico, Miki Sato, Masaji Sakaguchi, Motoyuki Igata, Takeshi Matsumura, Hirofumi Kai, Eiichi Araki, Naoto Kubota","doi":"10.1007/s13340-026-00886-6","DOIUrl":"10.1007/s13340-026-00886-6","url":null,"abstract":"<p><p>Heat shock protein 72 (HSP72) plays a protective role against metabolic stress through suppression of c-Jun N-terminal kinase (JNK). While HSP72 has been extensively studied in insulin-sensitive tissues and pancreatic β-cells, its role in regulating glucagon secretion in α-cells remains unclear. Because glucagon secretion is enhanced by stress-responsive kinases including JNK, we hypothesized that HSP72 may negatively regulate glucagon secretion. To evaluate the effects of HSP72 on glucagon regulation, HSP72 induction was achieved using a combination of heat shock (HS) and mild electrical stimulation (MES) in <i>db/db</i> mice. In vitro, αTC cells were treated with HS + MES, transfected with HSP72 overexpression plasmids, or subjected to HSP72 knockdown. Glucagon secretion, JNK phosphorylation, insulin signaling, and expression of glucagon-related transcription factors were analyzed. Pancreatic islets were isolated from wild-type (WT) and HSP72-knockout (KO) mice to assess glucagon secretion under basal, inflammatory, and metabolic stress conditions. HS + MES-treated <i>db/db</i> mice showed reduced fasting and random glucagon levels, accompanied by increased pancreatic HSP72 expression and decreased glucagon-positive islet area. In αTC cells, HSP72 induction suppressed TNF-α-induced glucagon secretion and JNK phosphorylation while restoring insulin-induced Akt phosphorylation. HSP72 knockdown abolished these protective effects. Islets from KO mice secreted significantly more glucagon under inflammatory (TNF-α) and metabolic (high-fat diet) stress. HSP72 overexpression decreased Pax6 and MafB mRNA levels, indicating transcriptional suppression of proglucagon expression. HSP72 suppresses glucagon secretion by inhibiting JNK activation, improving insulin signaling, and downregulating key glucagon transcription factors in α-cells. These findings identify HSP72 as a novel regulator of α-cell stress responses and a potential therapeutic target for glucagon dysregulation in diabetes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00886-6.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"34"},"PeriodicalIF":1.1,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teleguidance by physiotherapists maintains the quality of life in older patients with diabetic polyneuropathy: subanalysis of the TelePhysioT2D trial.","authors":"Takuo Nomura, Hiroaki Kataoka, Hiroyuki Oka, Yukio Ikeda","doi":"10.1007/s13340-026-00884-8","DOIUrl":"10.1007/s13340-026-00884-8","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetic polyneuropathy (DPN) decreases health-related quality of life (HRQOL) and physical function. Exercise therapy improves the physical function of patients with DPN; however, its effect on HRQOL remains unknown. Therefore, we subanalyzed the effect that teleguidance for exercise therapy by physiotherapists has on HRQOL in older patients with DPN by using our previously obtained data.</p><p><strong>Methods: </strong>The physiotherapist who participated in this study is a specialist in exercise therapy for diabetes. Participants with DPN were categorized into the teleguidance for exercise therapy by physiotherapists (TelePhysio) and control groups (<i>n</i> = 18 and 19, respectively). Both groups underwent the same moderate-intensity exercise therapy program. In the TelePhysio group, teleguidance for exercise therapy was provided for 30 min once a week for six months. In the control group, no telephone intervention was provided, and patients were interviewed at the hospital only at 3 months after discharge.</p><p><strong>Results: </strong>For the comparison between parameters at baseline and six months later, in the TelePhysio group, the EuroQol 5-dimensional (EQ-5D) score and knee extension force (KEF) did not decrease, whereas the Diabetes Treatment Satisfaction Questionnaire (DTSQ) score significantly improved (24.2 ± 5.7 to 26.7 ± 6.0; <i>P</i> < 0.05). In contrast, in the control group, the EQ-5D score and KEF were significantly decreased, whereas the DTSQ score remained unchanged.</p><p><strong>Conclusions: </strong>TelePhysio is effective in improving treatment satisfaction and may help prevent decline in HRQOL and physical function in older patients with DPN. Our findings suggest that TelePhysio may be a treatment option for older patients with DPN.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00884-8.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"33"},"PeriodicalIF":1.2,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective real-world database study to examine the prevalence and incidence of cardiovascular diseases and medication prescription in Japanese patients with type 2 diabetes.","authors":"Mitsuhisa Komatsu, Hiroshi Kobayashi, Satoshi Tsuboi, Hirotaka Watada","doi":"10.1007/s13340-026-00877-7","DOIUrl":"10.1007/s13340-026-00877-7","url":null,"abstract":"<p><strong>Introduction: </strong>In Japan, real-world characterisation of cardiovascular disease (CVD) prevalence, incidence, and medication prescription in adults with type 2 diabetes (T2D) has been limited.</p><p><strong>Methods: </strong>This real-world study (comprising a cross-sectional and a retrospective study) in adults aged ≥ 20 years with T2D used the Medical Data Vision database to evaluate the prevalence and incidence of three-point major adverse cardiovascular events (3P-MACE) and composite CVD and to describe medication prescription patterns.</p><p><strong>Results: </strong>The cross-sectional study included 292,383 patients in 2014 and 622,531 in 2021. Prevalence of 3P-MACE and composite CVD were 4.8% and 12.1%, respectively, in 2014; values in 2021 were 5.0% and 14.0%. In 2014, 2.1% of patients received glucagon-like peptide-1 receptor agonists (GLP-1RAs) and 0.8% received sodium-glucose cotransporter-2 inhibitors (SGLT-2is); 2021 values were 9.2% and 32.3%. The retrospective study included 314,206 patients; 19.7% had a CVD history. The overall incidence rate of 3P-MACE per 1000 person-years was 12.8 (95% confidence interval [CI] 12.6-13.0); 46.6 (45.3-48.0) in those with and 8.6 (8.4-8.8) in those without CVD history. The incidence rates (95% CI) of composite CVD were 47.9 (47.4-48.3); 179.5 (177.0-182.1) in those with and 31.5 (31.1-31.9) in those without CVD history.</p><p><strong>Conclusions: </strong>In Japan, the prevalence of 3P-MACE and composite CVD were almost unchanged from 2014 to 2021, whereas GLP-1RA/SGLT-2i prescriptions increased. Incidence rates of 3P-MACE and composite CVD were higher in patients with a CVD history. These data provide insights into prescription patterns in T2D in Japan and could inform future treatment practices.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13340-026-00877-7.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"31"},"PeriodicalIF":1.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RFX6 expression is central to the development and function of the neuroendocrine compartments of the pancreas and intestine and strongly affects diabetes risk.","authors":"Thomas S R Bate, Yuanhao Huang, Xin Luo, Diane C Saunders, John T Walker, Vivek Rai, Stephen C J Parker, Jie Liu, Marcela Brissova","doi":"10.1007/s13340-025-00867-1","DOIUrl":"10.1007/s13340-025-00867-1","url":null,"abstract":"<p><p>Transcription factors are central to the developmental and functional regulation of cells through co-ordination of gene expression via interaction with the genome. RFX6 is a winged-helix transcription factor whose expression is highly specific to the pancreas and gastrointestinal tract. Recent developments have highlighted an association between RFX6 and Type 2 Diabetes (T2D), which affects over 500 million people throughout the world. RFX6 controls development in both the pancreas and the gastrointestinal tract, where it is required for the differentiation of islet endocrine and enteroendocrine cells. Coding and non-coding <i>RFX6</i> variants have been associated with syndromic neonatal diabetes (Mitchell-Riley Syndrome), Maturity Onset Diabetes of the Young (MODY), and T2D. Given the central position of RFX6 in pancreatic development and diabetes, understanding in more detail the regulatory role of RFX6 in different cell types and at different stages of development may open avenues towards patient-specific diabetes treatment and prevention. In this article, we review the literature surrounding RFX6 with respect to its role in development and diabetes pathogenesis.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"23"},"PeriodicalIF":1.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigational treatments of β-cell failure and replacement.","authors":"Domenico Accili, Wen Du, Takumi Kitamoto, Wendy McKimpson, Jinsook Son, Hitoshi Watanabe","doi":"10.1007/s13340-026-00878-6","DOIUrl":"10.1007/s13340-026-00878-6","url":null,"abstract":"<p><p>Diabetes is associated with β-cell destruction (Type 1) or functional failure (Type 2). Our research has shown that β-cell failure in Type 2 Diabetes is secondary to the progression of β-cell dedifferentiation. Until recently, it was unclear whether the process was reversible. By analyzing the molecular underpinning of β-cell dedifferentiation, we identified ectopic activation of the enzyme aldehyde dehydrogenase subtype 1A3 (ALDH1A3) as an early marker and effector of the process. Although the signaling pathways by which activation of ALDH1A3 impinges on β-cell function are still to be determined, the enzyme provides a tractable pharmacological target. We have shown that a proprietary, highly potent, and specific ALDH1A3 inhibitor can reverse β-cell dysfunction in animals. Clinical trials of a further version of this compound are being readied. Another area of our interest is the treatment of Type 1 Diabetes by conversion of intestinal epithelial cells into glucose-responsive insulin-producing, β-like cells. We have developed small molecule FoxO1 inhibitors that, when administered orally to diabetic rodents, can lower glycemia and generate insulin-immunoreactive intestinal cells. These cells can also be generated in NOD mice and lead to a restoration of insulin production, demonstrating that they are resistant to autoimmunity. Further preclinical studies are underway to test safety and efficacy of this approach as a Type 1 Diabetes treatment.</p>","PeriodicalId":11340,"journal":{"name":"Diabetology International","volume":"17 2","pages":"25"},"PeriodicalIF":1.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}