Diabetes & metabolism最新文献

{"title":"Lower glucagon response and attenuated hepatic glucagon signaling in MASLD","authors":"So Ra Kim,&nbsp;Yeseong Hwang,&nbsp;Minyoung Lee,&nbsp;Arim Choi,&nbsp;Byung-Wan Lee,&nbsp;Eun Seok Kang,&nbsp;Bong-Soo Cha,&nbsp;Kwang Joon Kim,&nbsp;Yong-ho Lee","doi":"10.1016/j.diabet.2026.101787","DOIUrl":"10.1016/j.diabet.2026.101787","url":null,"abstract":"<div><h3>Background</h3><div>While glucagon plays a role in hepatic lipid metabolism, alterations in circulating glucagon profiles and hepatic glucagon signaling in metabolic dysfunction-associated steatotic liver disease (MASLD) in humans remain unclear. We aimed to investigate the relationship between MASLD severity and plasma glucagon dynamics, and evaluate hepatic glucagon signaling using human liver tissue.</div></div><div><h3>Methods</h3><div>This retrospective cross-sectional study included 137 adults with prediabetes or type 2 diabetes who underwent a 75 g oral glucose tolerance test (OGTT) with fasting and 2-h plasma glucagon measurements. MASLD severity was assessed using noninvasive scores and transient liver elastography. To evaluate hepatic glucagon signaling across MASLD severity, human liver tissue transcriptome and single-nucleus RNA sequencing (snRNA-seq) were analyzed.</div></div><div><h3>Results</h3><div>Participants with moderate-to-severe hepatic steatosis or high-risk metabolic dysfunction-associated steatohepatitis exhibited a lower integrated glucagon response, assessed by glucagon AUC during the 2-h OGTT, than their respective control groups (46,500 vs. 60,480 pg·min/ml, <em>P</em> = 0.006; and 43,680 vs. 52,620 pg·min/ml, <em>P</em> = 0.014, respectively). In contrast, there was no significant association between plasma glucagon levels and fibrosis severity. Transcriptomic analyses revealed downregulation of the glucagon receptor <strong>(</strong>GCGR<strong>)</strong> and downstream signaling pathways in liver tissues from individuals with MASLD, particularly within hepatocytes from those with advanced disease.</div></div><div><h3>Conclusion</h3><div>Among individuals with prediabetes or type 2 diabetes, greater hepatic steatosis and inflammation are associated with lower circulating glucagon levels and attenuated hepatic glucagon signaling. These findings may provide a basis for future investigation of glucagon-based therapeutic approaches.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 5","pages":"Article 101787"},"PeriodicalIF":5.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent burden and management gaps of hypoglycemia in pediatric type 1 diabetes: insights from the Epi-GLUREDIA Study","authors":"Maude Beckers,&nbsp;Antoine Harvengt,&nbsp;Gaetan de Valensart Schoenmaeckers,&nbsp;Dominique Beckers,&nbsp;Laure Boutsen,&nbsp;Thierry Mouraux,&nbsp;Inge Gies,&nbsp;Willem Staels,&nbsp;Jesse Vanbesien,&nbsp;Philippe A. Lysy","doi":"10.1016/j.diabet.2026.101774","DOIUrl":"10.1016/j.diabet.2026.101774","url":null,"abstract":"<div><h3>Background/Objectives</h3><div><em>-</em> Despite advances in automated insulin delivery, hypoglycemia remains a major challenge in pediatric type 1 diabetes. We aimed to characterize, in real-world practice, the burden, awareness, and daily-life impact of hypoglycemia and severe hypoglycemia (SH), and to identify gaps in perception and management.</div></div><div><h3>Methods</h3><div><em>-</em> We conducted a prospective, descriptive, multicenter study using the new GLUREDIA questionnaire, administered during routine pediatric diabetes visits across six centers in Belgium and Luxembourg. This structured, study-specific, semi-quantitative tool assessed hypoglycemia frequency, symptom severity, perceived glycemic thresholds, SH history and management, and post-SH behavioral adaptations. Hypoglycemia awareness was evaluated using items aligned with Clarke score domains.</div></div><div><h3>Results</h3><div><em>-</em> Among 232 participants, 55.9% reported hypoglycemia at least weekly, with moderate-to-high symptom severity. Cognitive and daily-life symptoms (impaired focus, fatigue, hunger, tremor) were reported by &gt;60% and interfered with activities. Hypoglycemia was identified as the dominant disease burden by 39.7% of participants. Hypoglycemia-related symptom burden remained substantial and was not fully explained by CGM-derived metrics. SH was reported by 45.7%, without clear cause in 29.1%. Recommended management, including glucagon use, was inconsistently applied, even in recurrent SH. Following SH, participants reported insulin dose reductions (27.4%), increased sugar intake (21.1%), and avoidance of physical activities (22.1%), as adaptations. The Epi-GLUREDIA questionnaire demonstrated promising discriminative ability against the Clarke score (AUC = 0.84), supporting its construct validity.</div></div><div><h3>Conclusions</h3><div><em>-</em> Despite advances in diabetes technology, hypoglycemia remains highly prevalent, impactful, and often poorly anticipated in pediatric type 1 diabetes. Gaps in SH management and hypoglycemia awareness, together with post-event adaptations, highlight the need for integrated strategies combining education, behavioral support, optimized use of technologies, and improved implementation of guidelines, including appropriate glucagon use, to improve hypoglycemia safety, recognition, and long-term outcomes in pediatric type 1 diabetes.</div></div><div><h3>Summary</h3><div>Hypoglycemia remains frequent and impactful in pediatric type 1 diabetes, with variable symptom thresholds, unexplained severe hypoglycemia, management gaps, and post-event adaptations that may impair glycemic control.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 4","pages":"Article 101774"},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like peptide-1 receptor agonists and risk of pancreaticobiliary cancers in patients with type 2 diabetes: a nationwide cohort study","authors":"Byeong Geun Song,&nbsp;Tae-Se Kim,&nbsp;Bong Seong Kim,&nbsp;Kyungdo Han,&nbsp;Byung-Hoon Min","doi":"10.1016/j.diabet.2026.101776","DOIUrl":"10.1016/j.diabet.2026.101776","url":null,"abstract":"<div><h3>Aim</h3><div>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated substantial metabolic benefits, but their association with pancreaticobiliary cancer risk remains unclear. We investigated the association between GLP-1RA use and pancreaticobiliary cancer incidence in patients with type 2 diabetes (T2D).</div></div><div><h3>Methods</h3><div>This population-based cohort study used Korean National Health Insurance Service data from 2011 to 2023. We identified 51,780 patients with T2D receiving metformin plus sulfonylurea who initiated either GLP-1RA (n=24,052) or dipeptidyl peptidase-4 inhibitor (DPP-4i, n=27,728). The primary outcomes were incident pancreatic cancer, bile duct cancer, gallbladder cancer, and composite pancreaticobiliary cancer. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for demographics, comorbidities, and previous diabetes medications.</div></div><div><h3>Results</h3><div>During 208,992 person-years of follow-up (mean 4.0 years), 321 pancreaticobiliary cancers occurred. GLP-1RA use was associated with a significantly lower risk of pancreatic cancer (adjusted HR 0.668, 95% CI 0.476-0.939). Similar trends were observed for bile duct cancer (adjusted HR 0.649, 95% CI 0.375-1.124), gallbladder cancer (adjusted HR 0.418, 95% CI 0.171-1.019), and composite pancreaticobiliary cancer (adjusted HR 0.681, 95% CI 0.515-0.901). These associations remained consistent in a propensity score–matched analysis and after excluding patients with baseline pancreaticobiliary disease.</div></div><div><h3>Conclusion</h3><div>In this large cohort study, GLP-1RA use was associated with reduced pancreatic cancer risk compared with DPP-4i use among patients with T2D. Similar trends were observed for other pancreaticobiliary cancers. These findings suggest potential protective effects that warrant confirmation in longer-term studies.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 4","pages":"Article 101776"},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CGM-based metrics and mortality in older adults living with type 2 diabetes on insulin therapy: a secondary analysis of the HYPOAGE study","authors":"Sarra Smati,&nbsp;Anne-Sophie Boureau,&nbsp;Pierre Gourdy,&nbsp;Béatrice Guyomarch,&nbsp;Cédric Annweiller,&nbsp;Claire Briet,&nbsp;Nathalie Cervantes,&nbsp;Laure de Decker,&nbsp;Isabelle Delabrière,&nbsp;Sophie Guyonnet,&nbsp;Marielle Joliveau,&nbsp;Rachel Litke,&nbsp;Pierre Morcel,&nbsp;Marc Paccalin,&nbsp;Alfred Penfornis,&nbsp;Pierre-Jean Saulnier,&nbsp;Samy Hadjadj,&nbsp;Bertrand Cariou","doi":"10.1016/j.diabet.2026.101775","DOIUrl":"10.1016/j.diabet.2026.101775","url":null,"abstract":"<div><h3>Aim</h3><div>Older adults living with type 2 diabetes represent a particularly vulnerable population. We investigated which continuous glucose monitoring (CGM)-derived targets are associated with all-cause mortality in this population.</div></div><div><h3>Methods</h3><div>HYPOAGE is prospective multicenter study including 141 insulin-treated older adults living with type 2 diabetes aged 75 and older, under insulin therapy for at least 6 months. All participants underwent standardized geriatric and diabetic assessments and wore an ambulatory blinded CGM (FreeStyle Libre Pro®) for 28 consecutive days. In this ancillary study, multivariable cox regressions were performed to identify factors associated with mortality after adjustment for age, sex, HbA_1c, kidney function, geriatric status, and metformin use.</div></div><div><h3>Results</h3><div>At baseline, participants were 81.5 years old on average. After a median follow-up of 44 months, 58 of 141 patients had died. In adjusted model, higher percentages of level 1 time below range (TBR), level 2 TBR and glycemic variability assessed by the coefficient of variation (CV) were independently associated with an increased mortality risk (hazard ratio [95% CI] 1.51 [1.11; 2.06], 1.25 [1.02; 1.53], and 1.76 [1.21; 2.56] for an interquartile range (IQR)% increase of each parameter, respectively). When recommended CGM targets were considered, only glycemic variability (CV ≤ 36%), remained significantly associated with a lower risk of mortality (hazard ratio 0.57 [0.32; 0.99]), whereas TIR &gt; 50% and TBR ≤ 1% were not.</div></div><div><h3>Conclusion</h3><div>Among insulin-treated older adults living with type 2 diabetes, glycemic variability was independently associated with all-cause mortality, highlighting its potential relevance for clinical management in geriatric diabetes care.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 4","pages":"Article 101775"},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased risk of new-onset osteoporosis in patients with Type 2 diabetes on SGLT-2 inhibitors","authors":"Chih-Feng Chang,&nbsp;Wei-Yao Wang,&nbsp;Pei-Lun Liao,&nbsp;Chih-Jung Yeh,&nbsp;Gwo-Ping Jong","doi":"10.1016/j.diabet.2026.101778","DOIUrl":"10.1016/j.diabet.2026.101778","url":null,"abstract":"<div><h3>Aims</h3><div>To evaluate the risk of new-onset osteoporosis (NOO) associated with sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes (T2D).</div></div><div><h3>Methods</h3><div>This population-based cohort study used Taiwan’s National Health Insurance Research Database. Participants were initially matched 1:2 on age, sex, and T2D duration between the SGLT2i and non-SGLT2i groups. Cox proportional hazards models assessed the association between SGLT2i use and the risk of NOO. Differences in osteoporosis risk over time between groups were also analyzed using the Kaplan–Meier method. A sensitivity analysis was then conducted using 1:1 propensity score matching.</div></div><div><h3>Results</h3><div>After matching on age, sex, and T2D duration, the study included 309,747 participants in the SGLT2i group and 619,494 in the non-SGLT2i group from 2016 to 2022. In the adjusted Cox model, SGLT2i use was associated with an 18% reduction in the risk of incident osteoporosis (adjusted hazard ratio [aHR]: 0.82, 95% confidence interval [CI]: 0.79–0.84). The sensitivity analysis using 1:1 propensity score matching included 274,329 patients per group, and SGLT2i use remained associated with a lower risk of osteoporosis (aHR: 0.83, 95% CI: 0.80–0.86). Kaplan–Meier analysis also showed that SGLT2i users had a lower incidence of NOO.</div></div><div><h3>Conclusion</h3><div>In real-world settings, patients with T2D treated with SGLT2is had a lower risk of NOO than those not using SGLT2is.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 4","pages":"Article 101778"},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two faces of autoimmune hyperinsulinemia: contrasting type B insulin resistance syndrome and exogenous insulin antibody syndrome","authors":"Huajie Zou,&nbsp;Xin Zheng,&nbsp;Siyi Wu,&nbsp;Tong Jiang,&nbsp;Xiaomei Ma,&nbsp;Ying Bai,&nbsp;Yuhong Li,&nbsp;Zilan Ma,&nbsp;Qiang Zhu,&nbsp;Shengmei Yang,&nbsp;Shenghua Ma,&nbsp;Ming Li,&nbsp;Ruixia Zhang","doi":"10.1016/j.diabet.2026.101777","DOIUrl":"10.1016/j.diabet.2026.101777","url":null,"abstract":"<div><h3>Aim</h3><div>To report two cases of immune-mediated severe hyperinsulinemia—Type B Insulin Resistance Syndrome (TBIRS) and Exogenous Insulin Antibody Syndrome (EIAS)—and to highlight the clinical clues for differential diagnosis and the divergent therapeutic strategies.</div></div><div><h3>Methods</h3><div>Detailed clinical, biochemical, and immunological evaluations of two patients with extreme hyperinsulinemia (&gt;350 µU/ml) and refractory hyperglycemia were performed, including polyethylene glycol (PEG) precipitation and insulin recovery assays.</div></div><div><h3>Results</h3><div>Patient 1, a 59-year-old woman with type 2 diabetes and pulmonary tuberculosis, had insulin levels exceeding 1000 µU/ml with positive anti-insulin receptor antibodies, confirming TBIRS. Active tuberculosis contraindicated immunosuppression and hyperglycemia persisted. Patient 2, a 61-year-old man with type 2 diabetes, had insulin levels of 767.7–833.9 µU/ml with strongly positive anti-insulin antibodies. PEG precipitation revealed an insulin recovery of 28.6% and a free-to-total insulin ratio of 6.8%, confirming EIAS. Insulin discontinuation and corticosteroids achieved glycemic control.</div></div><div><h3>Conclusion</h3><div>TBIRS and EIAS, though both presenting with extreme hyperinsulinemia, require fundamentally different management strategies. Comorbidities such as active tuberculosis may preclude immunosuppressive therapy in TBIRS, creating therapeutic dilemmas. In EIAS, when initial insulin modification fails to resolve glycemic instability, timely escalation to glucocorticoid therapy can achieve sustained immunological remission and durable glycemic control.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 4","pages":"Article 101777"},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equivalent fracture odds do not define equivalent treatment thresholds in diabetes","authors":"Yong Zhu,&nbsp;Jinjin Luo,&nbsp;Sheng Zheng","doi":"10.1016/j.diabet.2026.101764","DOIUrl":"10.1016/j.diabet.2026.101764","url":null,"abstract":"<div><div>None.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 3","pages":"Article 101764"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between primary bile acids and metabolically unhealthy obesity","authors":"Mingxi Zong ,&nbsp;Chao Wu ,&nbsp;Shaoqian Zhao ,&nbsp;Lijie Kong ,&nbsp;Wen Li ,&nbsp;Juan Shi ,&nbsp;Yufei Chen ,&nbsp;Yaorui Ye ,&nbsp;Aibo Gao ,&nbsp;Guang Ning ,&nbsp;Weiqing Wang ,&nbsp;Jiqiu Wang ,&nbsp;Weiqiong Gu ,&nbsp;Jie Hong ,&nbsp;Ruixin Liu","doi":"10.1016/j.diabet.2026.101761","DOIUrl":"10.1016/j.diabet.2026.101761","url":null,"abstract":"<div><h3>Objective</h3><div>Dysregulation of bile acid (BA) profiles is closely associated with obesity and its related metabolic abnormalities. This study aims to investigate the BA alterations between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and identify specific BA species associated with MUO.</div></div><div><h3>Methods</h3><div>We measured serum bile acid profiles in two cross-sectional studies. The discovery cohort included 261 normal-weight, 80 MHO, and 120 MUO individuals. The validation cohort, consisting of 104 MHO and 104 MUO participants (matched for age, sex, and BMI), was used for confirmation.</div></div><div><h3>Results</h3><div>Individual primary bile acids (PBAs), including cholic acid, glycocholic acid, chenodeoxycholic acid, and total PBA concentration, were markedly increased in MUO compared with both normal-weight and MHO subjects. Total secondary bile acids were decreased in both obesity phenotypes compared with normal-weight subjects, but did not differ between MUO and MHO. Among individuals with obesity, either individual PBA or total PBA levels were positively correlated with metabolic deterioration parameters such as WHR, HOMA-IR, HbA1c, and TG. Moreover, a higher total PBA level was associated with an increased proportion of MUO. These findings were further replicated in the validation cohort.</div></div><div><h3>Conclusions</h3><div>Serum individual PBAs and total PBAs were significantly elevated in MUO compared with MHO. Higher PBA levels were associated with adverse metabolic parameters and an increased proportion of MUO. This study characterizes the distinct BA profiles across obesity phenotypes and highlights the associations between PBAs and MUO.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 3","pages":"Article 101761"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why glycemic control remains suboptimal in type 1 diabetes in the era of advanced technologies?","authors":"Michael Joubert","doi":"10.1016/j.diabet.2026.101763","DOIUrl":"10.1016/j.diabet.2026.101763","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) remains associated with suboptimal glycemic control in a substantial proportion of individuals despite major advances in insulin formulations and technological systems. This apparent paradox highlights that glucose control in T1D is not determined by technology alone, but rather emerges from the interaction of multiple biological, therapeutic, behavioral, and psychosocial factors. In this structured narrative review, we examine the main determinants that continue to limit optimal control in real-world practice. Pathophysiological barriers include residual or absolute insulin deficiency, impaired counterregulatory responses, chronic or acute insulin resistance, hormonal changes related to puberty, the menstrual cycle and pregnancy, physical activity, and advanced renal disease. Therapeutic and technological progress has improved glycemic safety and time in range, yet insulin therapy remains an imperfect substitute for physiological insulin secretion, and the effectiveness of CGM, insulin pumps, connected pens, and AID systems remains highly dependent on sustained and appropriate use. Behavioral determinants such as treatment adherence, meal bolusing, carbohydrate estimation, physical activity management, and technology misuse continue to be major drivers of glycemic variability. In parallel, psychosocial factors, including eating disorders, anxiety, depression, stress, socioeconomic vulnerability, and shift work, strongly influence self-management and may further aggravate metabolic instability. These determinants interact dynamically and bidirectionally, creating self-reinforcing cycles that help explain why recommended glycemic targets remain difficult to achieve. Improving outcomes in T1D therefore requires moving beyond a technology-centered model toward an integrated, patient-centered approach that combines technological innovation with therapeutic education, psychosocial screening, and individualized care across the life course.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 3","pages":"Article 101763"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone phenotype in familial partial lipodystrophy type 2: Insulin resistance and sclerostin","authors":"Hippolyte Dupuis ,&nbsp;Arnaud Jannin ,&nbsp;Lucille Van Es ,&nbsp;Romain Vankemmel ,&nbsp;Olivier Ernst ,&nbsp;Pascal Pigny ,&nbsp;Georges Lion ,&nbsp;Benjamin Chevalier ,&nbsp;Bernard Cortet ,&nbsp;Stéphanie Espiard ,&nbsp;Marie-Christine Vantyghem","doi":"10.1016/j.diabet.2026.101762","DOIUrl":"10.1016/j.diabet.2026.101762","url":null,"abstract":"<div><h3>Background</h3><div>The impact of insulin-resistance on bone mineral density (BMD) remains unclear. Sclerostin inhibits bone formation, and increases with ageing, metabolic syndrome, and renal failure. Genetically-determined low sclerostin levels are associated with high BMD. Our aim was to determine the bone phenotype and the influence of insulin-resistance without obesity on sclerostin levels in Familial Partial Lipodystrophy type 2 (FPLD2).</div></div><div><h3>Methods</h3><div>Demographic, metabolic, anthropometric, and bone parameters were compared after adjustment on age and menopausal status across four groups of women (19 FPLD2, 12 obese with diabetes, 14 obese without diabetes, 11 lean controls).</div></div><div><h3>Results</h3><div>The FPLD2 group had significantly higher Intra-Abdominal/Total-Abdominal Fat (IAF/TAF) ratio and lower fat mass percentage compared to the other groups. Glucose parameters (Fasting blood glucose, C-peptide, HbA1c, HOMA2-IR_CP), and triglycerides were significantly higher in the FPLD2 group than in controls, with a higher sclerostin level. Sclerostin levels were positively associated with age, glucose parameters, Z-score, T-score, and negatively with osteocalcin. FPLD2 was the only subgroup in which the association between sclerostin and HOMA2-IR_CP was maintained. In contrast, osteocalcin levels were negatively associated with age, glucose parameters, triglycerides, IAF/TAF, and bone parameters. Neither sclerostin or osteocalcin were associated with BMI, whole-body fat, or leptin.</div></div><div><h3>Conclusion</h3><div>The association of sclerostin (positive) and osteocalcin (negative) with HOMA2-IR_CP, but not with fat mass parameters, suggests a predominant role of insulin-resistance over fat mass in the regulation of osteokines. Insulin-resistance may uncouple the usual relationship between sclerostin and BMD. The sclerostin contribution in early atherosclerosis in FPLD2 remains to be studied.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"52 3","pages":"Article 101762"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}