Diabetologia最新文献

{"title":"Evolving phenotype of newly diagnosed type 2 diabetes: a 15-year population-based comparison.","authors":"Dani Kirshner, Michael Hauzer","doi":"10.1007/s00125-026-06901-4","DOIUrl":"https://doi.org/10.1007/s00125-026-06901-4","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Our aim was to describe the phenotype at diagnosis and the early therapeutic profile of newly diagnosed type 2 diabetes across two periods spanning approximately 15 years within the same integrated healthcare system.</p><p><strong>Methods: </strong>This retrospective cohort study used electronic health record data from Clalit Health Services (Haifa & Western Galilee, Israel). Adults with incident type 2 diabetes in 2005-2008 (period 1: n=80,201) were compared with those diagnosed in 2020-2023 (period 2: n=101,392). Between-period differences are presented as crude estimates, with an age-stratified sensitivity analysis, and quantified using standardised mean differences (SMDs; values ≥0.20 indicate at least a small effect) alongside non-parametric and χ² tests.</p><p><strong>Results: </strong>The median age at diagnosis increased from 63.0 to 66.7 years between the two periods; the proportion aged ≥85 years nearly doubled (from 3.5% to 6.6%). The score for the Charlson comorbidity index increased from 4 to 6 (SMD 0.48); metabolic dysfunction-associated steatotic liver disease (MASLD) increased from 4.4% to 18.6%. HbA_1c at diagnosis decreased from 56 to 53 mmol/mol (7.3% to 7.0%); pre-diagnosis LDL-cholesterol decreased from 2.90 to 2.21 mmol/l (SMD 0.65). Within 31-90 days of diagnosis, use of sodium-glucose cotransporter 2 (SGLT2) inhibitors increased from 0.07% to 15.0%, use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) increased from 0% to 11.1%, and sulfonylurea use decreased more than fourfold (20.8% to 4.5%).</p><p><strong>Conclusions/interpretation: </strong>The phenotype of newly diagnosed type 2 diabetes has been fundamentally restructured since 2008: patients are older with a higher comorbidity burden but present with better glycaemic and lipid management, with the latter reflecting statin therapy already established before diagnosis. MASLD has emerged as a major but largely ascertainment-driven comorbidity. The shift to SGLT2 inhibitors and GLP-1RAs alongside declining sulfonylurea use indicates displacement of glucose-centric strategies by a cardiorenal- and weight-driven paradigm. These findings indicate a need for age-appropriate management and trials enrolling very elderly patients.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered glucagon and GIP responses in South Asian versus Nordic women after gestational diabetes mellitus.","authors":"Archana Sharma, Sindre Lee-Ødegård, Jens Juul Holst, Bolette Hartmann, A Anita S Kvist, Elisabeth Qvigstad, Stina T Sollid, Ingrid Nermoen, Kåre I Birkeland","doi":"10.1007/s00125-026-06898-w","DOIUrl":"https://doi.org/10.1007/s00125-026-06898-w","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>We aimed to compare ethnic differences in levels of glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) following a pregnancy complicated by gestational diabetes mellitus (GDM), and to assess whether the higher insulin levels observed in South Asian compared with Nordic women could be explained by differences in the hormone secretory responses.</p><p><strong>Methods: </strong>We measured glucagon, GIP and GLP-1 in 178 South Asian and 107 Nordic women during an OGTT, and stratified participants by glycaemic status. Glucagon and total GLP-1 and GIP responses when fasting and post-OGTT were assessed by linear mixed models. Ethnic differences in incretin and glucagon levels were evaluated by linear regression analyses. Pre-hepatic insulin levels were estimated using deconvolution of C-peptide kinetics.</p><p><strong>Results: </strong>Ethnic differences in glucagon and incretin levels varied by glycaemic status. In the normoglycaemic South Asian group, early (0-15 min) glucagon suppression post-OGTT was significantly attenuated compared with the Nordic group (p=0.002). Fasting glucagon levels did not differ (p=0.139), but total glucagon exposure (including fasting levels) was higher in South Asian women (p=0.013). No differences in GIP and GLP responses to the OGTT were observed (p=0.490 and p=0.802). In women with prediabetes or diabetes, fasting glucagon was higher in the South Asian group (p=0.010), but there were no significant differences in early glucagon suppression post-OGTT (p=0.986). GIP responses to the OGTT were lower among South Asian women (p<0.001), despite higher insulin responses compared with the Nordic women. GLP-1 responses did not differ between the ethnic groups (p=0.661). The higher pre-hepatic insulin levels in South Asian vs Nordic normoglycaemic women were not associated with differences in incretin levels, but were associated with lower insulin sensitivity in the regression analyses (p<0.001).</p><p><strong>Conclusions/interpretation: </strong>When examined 1-3 years post-GDM, normoglycaemic South Asian women had less early glucagon suppression and higher total glucagon exposure post-OGTT compared with Nordic women. The higher pre-hepatic insulin levels were not associated with higher incretin levels, but were associated with lower insulin sensitivity.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of HRS-7535, a novel oral small-molecule glucagon-like peptide-1 receptor agonist, in participants with type 2 diabetes mellitus inadequately controlled by metformin and sodium-glucose co-transporter 2 inhibitors: a multicentre, randomised, double-blind, placebo-controlled, parallel-group Phase II trial.","authors":"Mingtong Xu, Weihong Song, Fang Lv, Yanqin Fu, Liu Yang, Xiaochang Bin, Xiting Zhang, Zi Ye, Danli Zhang, Xiang Lin, Wei Dai, Chang Shu, Li Yan","doi":"10.1007/s00125-026-06892-2","DOIUrl":"https://doi.org/10.1007/s00125-026-06892-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;This study aimed to evaluate the efficacy and safety of HRS-7535, an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1RA), in Chinese participants with type 2 diabetes mellitus inadequately managed by metformin and sodium-glucose co-transporter 2 inhibitors (SGLT2i).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicentre, randomised, double-blind, placebo-controlled, Phase II study included participants aged 18-75 years with type 2 diabetes, HbA&lt;sub&gt;1c&lt;/sub&gt; 58-97 mmol/mol (7.5-11.0%) and BMI 20.0-35.0 kg/m&lt;sup&gt;2&lt;/sup&gt; and on stable-dose metformin and sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy for ≥8 weeks prior to screening. Participants were assigned in a 1:1:1 ratio to receive HRS-7535 30 mg, HRS-7535 60 mg or visually matching placebo tablets once daily using a stratified block randomisation method, with treatment assignments concealed until study completion. The primary endpoint was the change in HbA&lt;sub&gt;1c&lt;/sub&gt; from baseline to week 16. Secondary efficacy outcomes included the proportions of participants achieving HbA&lt;sub&gt;1c&lt;/sub&gt; targets of &lt;53 mmol/mol (7.0%) and ≤48 mmol/mol (6.5%), and changes from baseline in fasting body weight to week 16.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 155 participants with a mean baseline HbA&lt;sub&gt;1c&lt;/sub&gt; of 69 mmol/mol (8.5%) were randomly assigned to HRS-7535 30 mg (n=51), HRS-7535 60 mg (n=53) or placebo (n=51). At week 16, the least‑squares mean differences in HbA&lt;sub&gt;1c&lt;/sub&gt; from baseline for the HRS-7535 30 mg, HRS-7535 60 mg and placebo groups were -16 mmol/mol (95% CI -19, -14) (-1.5% [95% CI -1.7, -1.3]), -20 mmol/mol (95% CI -22, -17) (-1.8% [95% CI -2.0, -1.6]) and -4 mmol/mol (95% CI -7, -2) (-0.4% [95% CI -0.6, -0.2]), respectively (p&lt;0.0001 for both HRS-7535 doses vs placebo). The proportions of participants achieving HbA&lt;sub&gt;1c&lt;/sub&gt; &lt;53 mmol/mol (7.0%) were 51.0% in the HRS‑7535 30 mg group, 66.0% in the HRS‑7535 60 mg group, and 9.8% in the placebo group; the corresponding proportions for HbA&lt;sub&gt;1c&lt;/sub&gt; ≤48 mmol/mol (6.5%) were 35.3%, 37.7% and 3.9%, respectively. Body weight loss was -2.4% in the HRS-7535 60 mg group vs -0.7% in the placebo group. Most treatment-emergent adverse events (TEAEs) were mild to moderate, and gastrointestinal adverse events were the most common. No severe hypoglycaemia was reported. The only TEAE that led to treatment discontinuation occurred in the placebo group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;Treatment with HRS-7535 resulted in significant improvements in glycaemic management in participants with type 2 diabetes, and the drug exhibited a favourable safety profile. To address a significant clinical data void, this research focused on the addition of HRS‑7535 to the background regimen of metformin and SGLT2i for glycaemic management in participants with type 2 diabetes. Trial registration ClinicalTrials.gov NCT06393348. Funding This study was funded by Jiangsu Hengrui Phar","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose controls metallothionein 1 gene expression in pancreatic islets via a mechanism involving cellular metabolism, granular zinc and the zinc transporter ZnT8 in rat and mouse.","authors":"Rui Cheng, Can Zhao, Nan Guan, LingZhi Yue, Dan Ma, Moustapha Ka, Kailun Lee, D Ross Laybutt, Jean-Christophe Jonas, Mohammed Bensellam","doi":"10.1007/s00125-026-06900-5","DOIUrl":"https://doi.org/10.1007/s00125-026-06900-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Metallothionein 1 (MT1) negatively regulates insulin secretion in pancreatic beta cells, and is upregulated by low non-stimulating glucose levels compared with physiological glucose stimulation in cultured rodent and human islets. Whether this regulation also occurs in vivo and its underlying mechanisms remain unclear. Here we examine whether physiological changes in blood glucose levels in vivo control islet Mt1 gene expression similarly to ex vivo observations, and identify the mechanisms involved.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Rats fasted for 1, 2 or 3 days and rats fasted for 2 days and refed for 1 day were compared with rats fed throughout. Mice implanted with subcutaneous insulin mini-osmotic pumps were compared with control mice. Rat and mouse islets were cultured in the presence of optimal glucose levels (10 mmol/l; G10 medium) or low non-stimulating glucose levels (2 or 5 mmol/l; G2 or G5 medium) in the absence or presence of various modulators of mitochondrial metabolism, protein synthesis, Ca&lt;sup&gt;2+&lt;/sup&gt; influx, autophagy and insulin secretion. Islets from Znt8 (Slc30a8) knockout (KO) mice and corresponding control mice were studied. Gene mRNA levels were assessed by reverse-transcription followed by real-time PCR, plasma and secreted insulin levels were assessed using RIA, intracellular free Zn&lt;sup&gt;2+&lt;/sup&gt; ([Zn&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;c&lt;/sub&gt;) was assessed using FluoZin-3, metal regulatory transcription factor 1 (MTF1) activity was assessed using an MTF1-luciferase lentiviral reporter system, and beta cell morphology was assessed by transmission electron microscopy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among glucose-affected zinc transporters/importers in rat islets, only the zinc efflux transporter Znt1 (Slc30a1) was upregulated under low non-stimulating glucose levels (G2 and G5 medium) vs physiological glucose stimulation (G10 medium), in parallel with Mt1. In vivo, Mt1 mRNA levels were upregulated approximately 3-4-fold in the islets of fasted rats and mice implanted with insulin pumps, with both conditions inducing sustained hypoglycaemia. This effect was fully reversed after normalisation of blood glucose levels. Interestingly, Znt1 mRNA levels changed in parallel with those of Mt1. Hypoglycaemia also markedly altered the expression of beta cell-enriched genes (downregulated), adaptive unfolded protein response (UPR) genes (downregulated), integrated stress response (ISR)/proapoptotic UPR genes (upregulated) and oxidative stress-responsive genes (upregulated). Normalisation of blood glucose levels largely reversed these alterations. In cultured islets, addition to G2 medium of mitochondrial metabolic substrates that bypass glycolysis inhibited Mt1 expression to the same extent as G10 medium. Conversely, the reduction of Mt1 expression in G10 medium was prevented when mitochondrial function or protein synthesis were inhibited. In comparison with fed mice, beta cells of fasted mice had degradative aut","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No journal is an island.","authors":"Hindrik Mulder","doi":"10.1007/s00125-026-06889-x","DOIUrl":"https://doi.org/10.1007/s00125-026-06889-x","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic background modulates MafAS64F-mediated islet ageing in male mice","authors":"Zachary Loyd,Dongsoo Lee,Mallory Maurer,Lizabeth Johnson,Jin-Hua Liu,Garrett Reynolds,Mark P. Keller,Jean-Philippe Cartailler,Mark A. Magnuson,Roland Stein,Jeeyeon Cha","doi":"10.1007/s00125-026-06903-2","DOIUrl":"https://doi.org/10.1007/s00125-026-06903-2","url":null,"abstract":"Abstract Aims/hypothesis In monogenic diabetes, there is increasing recognition that common polygenic factors can modulate diabetes penetrance beyond the causative mutation(s). A naturally occurring mutation in the gene encoding the essential islet-enriched transcription factor MafA ( MafA S64F ) produces an unusually long-lived variant protein that predisposes male carriers to MODY. Here we investigated how genetic background modulates disease penetrance in Mafa S64F/+ male mice. Methods Mafa S64F/+ male mice, either on a mixed genetic background (C57BL/6J and SJL/J) or backcrossed to a C57BL/6J background, were assessed for glucose levels, beta cell function and gene signatures associated with cellular ageing. RNA-seq analysis was performed to identify unique differentially expressed genes (DEGS) and pathways in mixed-background or C57BL/6J Mafa S64F/+ male mouse islets. These were overlaid on MafA CUT&amp;RUN peaks to identify direct targets that could differentially impact beta cell function in each background. Results Mafa S64F/+ male mice on a mixed background manifested overt diabetes, impaired insulin secretion, accelerated beta cell senescence and dysregulated circadian gene expression, while backcross to C57BL/6J prevented dysglycaemia and maintained insulin secretion in Mafa S64F/+ male mice, comparable with control littermates. RNA-seq of C57BL/6J Mafa S64F/+ male mouse islets revealed relative normalisation of DEGs associated with cellular ageing and circadian regulation. In addition, islets from C57BL/6J Mafa S64F/+ male mice showed unique downregulation of retinoic acid signalling and cell cycle inhibitor p21, the latter of which modulates cellular ageing and diabetes seen in the mixed-background mouse islets. CUT&amp;RUN mapping revealed that MafA directly impacted expression of (at least) retinoic acid receptor-α (encoded by Rara ) in islets from C57BL/6J Mafa S64F/+ male mice and circadian regulation in islets from mixed-background mice. Conclusions/interpretation In sum, these data show that genetic modifiers can impact beta cell regulation of retinoic acid signalling and circadian entrainment to modulate beta cell ageing and disease penetrance in mice modelling MAFA -MODY. Data availability Sequencing data were deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (accession no. GSE299343 for bulk RNA-seq and GSE298664 for CUT&amp;RUN analyses).","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"104 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Expression of Concern: Critical role of c-Kit in beta cell function: increased insulin secretion and protection against diabetes in a mouse model","authors":"Z. C. Feng, J. Li, B. A. Turco, M. Riopel, S. P. Yee, R. Wang","doi":"10.1007/s00125-026-06894-0","DOIUrl":"https://doi.org/10.1007/s00125-026-06894-0","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"9 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CGM-derived disposition index estimates beta cell function in individuals with islet autoimmunity who do not require insulin treatment; changes in the disposition index precede changes identified by CGM metrics 1 year later","authors":"Hadija Marchiori,Michele Schiavon,Eileen Tichy,Michele Alguard,Marcia DeSousa,Simone Del Favero,Jason L. Gaglia,Jennifer L. Sherr,Chiara Dalla Man,Alfonso Galderisi","doi":"10.1007/s00125-026-06895-z","DOIUrl":"https://doi.org/10.1007/s00125-026-06895-z","url":null,"abstract":"Abstract Aims/hypothesis Monitoring of beta cell function in individuals with islet autoimmunity who do not require insulin treatment (preclinical type 1 diabetes) is normally done via OGTTs, posing major challenges given the invasiveness of the test. Here, we validated a disposition index (DI) derived from continuous glucose monitoring (CGM) metrics (DI CGM ), which is a proxy of beta cell function, against the gold-standard OGTT DI (DI MM ), in a cohort of individuals with one or more islet autoantibodies who do not require insulin treatment. Methods Participants underwent a 3 h 10-point OGTT with measurement of glucose, insulin and C-peptide while wearing a blinded CGM. The sensor was started 24 h prior to the OGTT. DI CGM was computed using CGM data during the 3 h OGTT and two blood glucose calibrations, and compared with the DI from the oral minimal model (DI MM ), which uses plasma glucose, insulin and C-peptide. The association between the baseline DI CGM and duration of glucose levels above 7.8 mmol/l (140 mg/dl) (TA140) at 1 year was explored. Results Twenty-four participants (median age 16.8 years [IQR 13.5–27.7] ) were enrolled, of whom 18 completed both the OGTT (ten with pre-stage 1, seven with stage 1 and one with stage 3a type 1 diabetes) and CGM at baseline, and had repeat CGM 1 year later. The baseline DI CGM was highly correlated with the DI MM ( r =0.90, p &lt;0.001). Lower baseline DI CGM was associated with higher 1 year TA140 ( r =−0.61, p =0.014) and higher 1 year mean sensor glucose ( r =−0.62, p =0.020). Conclusions/interpretation Beta cell function can be estimated using CGM during a glucose load. DI CGM correlates with a 1 year clinically relevant outcome (TA140) in individuals with islet autoimmunity who do not require insulin therapy.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"1 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asian men than European men: a potential mechanism underlying elevated type 2 diabetes risk","authors":"Mueed Azhar,Jieniean Worsley,Kaitlyn M. J. H. Dennis,Emanuella De Lucia Rolfe,Amy Barrett,Mandour O. Mandour,Enes Demir,Katherine Carr,Michele Ferraro,Ranalie De Jesus,Samuel King,Sherly Jose,Simon R. White,Peter Barker,Graham J. Kemp,Kevin M. Brindle,Krishna K. Chatterjee,Nita G. Forouhi,Michelle Venables,Laura Watson,Leanne Hodson,David B. Savage,Alison Sleigh","doi":"10.1007/s00125-026-06876-2","DOIUrl":"https://doi.org/10.1007/s00125-026-06876-2","url":null,"abstract":"Abstract Aims/hypothesis South Asian individuals are up to six times more likely to develop type 2 diabetes than individuals from other ethnic groups, often at a younger age and lower BMI. It has been shown that liver fat accumulates more readily in South Asian individuals, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in this population. However, the mechanisms underlying this phenomenon remain unclear. Understanding the role of de novo lipogenesis (DNL) in liver fat accumulation has been hampered by a lack of non-invasive techniques to quantify DNL-derived liver fat. We developed a method to quantify DNL-derived liver fat and used it in a proof-of-concept case–control study, hypothesising that there would be greater liver fat contribution from DNL in South Asian individuals than in European individuals. Methods A total of seven South Asian and six European participants, matched for age and BMI, underwent deuterium magnetic resonance scans at baseline and after 5 days of 2 H water enrichment, from which the fractional and absolute amounts of liver fat from DNL (DNL MR ) were calculated. Proton magnetic resonance spectroscopy ( 1 H-MRS) and MRI were used to determine lipid quantity and composition. Results Our method allowed precise quantification of 2 H-labelled liver lipids (intraclass correlation coefficient [ICC]&gt;0.956), which enabled us to accurately detect changes in liver fat due to DNL. Both fractional and absolute DNL MR were higher in South Asian participants than in European participants (both p =0.041). DNL MR correlated with liver fat content (fractional r s =0.874, absolute r s =0.888; both p =0.001), as well as the saturation ratio of both liver fat (fractional r s =0.692, absolute r s =0.748; both p &lt;0.05) and visceral adipose tissue (fractional r s =0.648, absolute r s =0.708; both p &lt;0.01). Liver fat content correlated with insulin resistance (HOMA-IR) ( r s =0.659, p =0.014). Conclusions/interpretation DNL or related factors may play a pivotal role in driving the increased liver fat and risk of diabetes in South Asian individuals. The novel methodology used to quantify DNL provides a powerful tool for studying DNL-derived liver fat in human metabolic disorders including diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"36 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visceral fat endocannabinoid overproduction is associated with insulin resistance and tissue dysfunction in mice and humans","authors":"Romain Barbosa,Julia Leemput,Patricia Passilly-Degrace,Océane Pointeau,Chloé Buch,Jean-Paul Pais de Barros,Maéva Loriot,Amélie Lainé,Lukas Buet,Pablo Ortega-Deballon,Bruno Vergès,Laurent Demizieux,Tony Jourdan,Pascal Degrace","doi":"10.1007/s00125-026-06886-0","DOIUrl":"https://doi.org/10.1007/s00125-026-06886-0","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"24 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}