Diabetologia最新文献

{"title":"Elevated risk of infection in individuals with hyperinsulinaemic type 2 diabetes: a Danish 12 year cohort study","authors":"Frederik P. B. Kristensen, Sidsel L. Domazet, Jens S. Nielsen, Jacob V. Stidsen, Kurt Højlund, Henning Beck-Nielsen, Peter Vestergaard, Niels Jessen, Michael H. Olsen, Torben Hansen, Charlotte Brøns, Allan Vaag, Henrik T. Sørensen, Reimar W. Thomsen","doi":"10.1007/s00125-024-06342-x","DOIUrl":"https://doi.org/10.1007/s00125-024-06342-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>A better understanding of the mechanisms underlying an elevated infection risk in individuals with type 2 diabetes is needed to guide risk stratification and prevention. We investigated the risk of infection in subgroups of individuals with type 2 diabetes according to indices of insulin sensitivity and beta cell function.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We classified 7265 individuals with recently diagnosed type 2 diabetes (median duration 1.4 years, IQR 0.5–2.9 years) into hyperinsulinaemic (high beta cell function [HOMA 2-beta-cell function, HOMA2-B], low insulin sensitivity [HOMA 2-insulin sensitivity, HOMA2-S]), classical (low HOMA2-B, low HOMA2-S) and insulinopenic (low HOMA2-B, high HOMA2-S) type 2 diabetes. Individuals were followed until first hospital-treated infection or first prescription for an anti-infective agent (community-treated infection). We used Cox regression analysis to estimate HRs adjusted for age, sex, index year, diabetes duration and treatment, lifestyle behaviours and comorbidities.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among study participants, 28% had hyperinsulinaemic, 63% had classical and 9% had insulinopenic type 2 diabetes. The 10 year risks of hospital-treated infections were 42.3%, 36.8% and 31.0% in the three subgroups, respectively. Compared with the insulinopenic subgroup, adjusted HRs for hospital-treated infections were elevated for hyperinsulinaemic (1.38 [95% CI 1.16, 1.65]) and classical type 2 diabetes (1.20 [95% CI 1.02, 1.42]). The 10 year risks of community-treated infections were high in all three subgroups at 91.6%, 90.1% and 88.3%, respectively, corresponding to adjusted HRs of 1.20 (95% CI 1.08, 1.33) for the hyperinsulinaemic and 1.10 (95% CI 1.00, 1.21) for the classical subgroup. Infection risk in the hyperinsulinaemic subgroup decreased substantially when further adjusted for abdominal obesity, metabolic derangements and low-grade inflammation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>The risk of severe infections is clearly elevated in individuals with type 2 diabetes characterised by a higher degree of insulin resistance/hyperinsulinaemia.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"113 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809086","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":"Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial","authors":"J. David Smeijer, Sieta T. de Vries, Donald E. Kohan, Fan Fan Hou, Hiddo J. L. Heerspink","doi":"10.1007/s00125-024-06326-x","DOIUrl":"https://doi.org/10.1007/s00125-024-06326-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>In the Study Of diabetic Nephropathy with AtRasentan (SONAR), the endothelin receptor antagonist (ERA) atrasentan slowed progression of chronic kidney disease (CKD) in individuals with type 2 diabetes. Pre-clinical research suggests sex-based differences in the endothelin system might influence the efficacy and safety of atrasentan. We therefore assessed the effects of atrasentan in men and women participating in SONAR.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>SONAR was a double-blind, placebo-controlled trial that compared atrasentan 0.75 mg/day with placebo in individuals with type 2 diabetes and CKD (eGFR 25–75 ml/min per 1.73 m², urine albumin/creatinine ratio [UACR] 300–5000 mg/g). The primary endpoint was defined as the time from randomisation to the first occurrence of a doubling in serum creatinine or kidney failure (eGFR &lt;15 ml/min per 1.73 m², chronic dialysis, kidney transplantation or death from kidney failure). Hospitalisation for heart failure was the secondary endpoint. We performed Cox proportional hazards regression analyses to compare the treatment effect of atrasentan between male and female participants on the risk of the composite kidney outcome as well as hospitalisation for heart failure. Additionally, differences between male and female participants in atrasentan plasma exposure and eGFR change were assessed using, respectively, a <i>t</i> test and linear mixed effect model.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 3668 randomised participants, 946 (25.8%) were female. Atrasentan significantly reduced the risk of the composite kidney outcome in female participants (HR 0.46 [95% CI 0.28, 0.76]) but not in male participants (HR 0.83 [95% CI 0.65, 1.05]; <i>p</i> value for interaction 0.032). Atrasentan compared with placebo reduced eGFR decline to a greater extent in female than in male participants (treatment effect difference between male vs female participants −0.99 ml/min per 1.73 m², <i>p</i> value for interaction=0.020). The RR for hospitalisation for heart failure with atrasentan vs placebo was 1.14 (95% CI 0.74, 1.76) in male participants and 1.88 (95% CI 0.98, 3.63) in female participants (<i>p</i> value for interaction=0.217). Female participants also had significantly higher atrasentan plasma exposure than male participants (geometric mean AUC 54.5 vs 42.6 ng/ml×h; <i>p</i>&lt;0.001).</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Atrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants. These data suggest that sex-specific dosing regimens may be considered to optimise ERA treatment.</p><h3 data-test=\"abstract-sub-heading\">Trial registration</h3><p>ClinicalTrials.gov NCT01858532</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"1 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804741","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":"The use of automated insulin delivery around physical activity and exercise in type 1 diabetes: a position statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD)","authors":"Othmar Moser, Dessi P. Zaharieva, Peter Adolfsson, Tadej Battelino, Richard M. Bracken, Bruce A. Buckingham, Thomas Danne, Elizabeth A. Davis, Klemen Dovč, Gregory P. Forlenza, Pieter Gillard, Sabine E. Hofer, Roman Hovorka, Peter G. Jacobs, Julia K. Mader, Chantal Mathieu, Kirsten Nørgaard, Nick S. Oliver, David N. O’Neal, John Pemberton, Rémi Rabasa-Lhoret, Jennifer L. Sherr, Harald Sourij, Martin Tauschmann, Jane E. Yardley, Michael C. Riddell","doi":"10.1007/s00125-024-06308-z","DOIUrl":"https://doi.org/10.1007/s00125-024-06308-z","url":null,"abstract":"<p>Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provide additional health benefits but can cause glucose fluctuations, which challenges current AID systems. While an increasing number of clinical trials and reviews are being published on different AID systems and PA, it seems prudent at this time to collate this information and develop a position statement on the topic. This joint European Association for the Study of Diabetes (EASD)/International Society for Pediatric and Adolescent Diabetes (ISPAD) position statement reviews current evidence on AID systems and provides detailed clinical practice points for managing PA in children, adolescents and adults with type 1 diabetes using AID technology. It discusses each commercially available AID system individually and provides guidance on their use in PA. Additionally, it addresses different glucose responses to PA and provides stratified therapy options to maintain glucose levels within the target ranges for these age groups.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"19 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797050","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":"Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials","authors":"Sieta T. de Vries, Michelle J. Pena, Sok Cin Tye, Sanne A. E. Peters, Daniël H. van Raalte, Clare Arnott, Adriaan A. Voors, Peter G. M. Mol, Petra Denig, Hiddo J. L. Heerspink","doi":"10.1007/s00125-024-06325-y","DOIUrl":"https://doi.org/10.1007/s00125-024-06325-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Included were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]).</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>This study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers’ efficacy and underlying mechanisms of differences in response is needed.</p><h3 data-test=\"abstract-sub-heading\">Trial registration</h3><p>ClinialTrials.gov NCT00308347</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"83 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797051","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":"Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function","authors":"Matthew E. Brown, Puchong Thirawatananond, Leeana D. Peters, Elizabeth J. Kern, Sonali Vijay, Lindsey K. Sachs, Amanda L. Posgai, Maigan A. Brusko, Melanie R. Shapiro, Clayton E. Mathews, Rhonda Bacher, Todd M. Brusko","doi":"10.1007/s00125-024-06329-8","DOIUrl":"https://doi.org/10.1007/s00125-024-06329-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Immunotherapeutics targeting T cells are crucial for inhibiting autoimmune disease progression proximal to disease onset in type 1 diabetes. There is an outstanding need to augment the durability and effectiveness of T cell targeting therapies by directly restraining proinflammatory T cell subsets, while simultaneously augmenting regulatory T cell (Treg) activity. Here, we present a novel strategy for preventing diabetes incidence in the NOD mouse model using a blocking monoclonal antibody targeting the type 1 diabetes risk-associated T cell co-stimulatory receptor, CD226.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Female NOD mice were treated with anti-CD226 at 7–8 weeks of age and then monitored for diabetes incidence and therapeutic mechanism of action.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Compared with isotype-treated controls, anti-CD226-treated NOD mice showed reduced insulitis severity (0.84-fold, <i>p</i>=0.0002) at 12 weeks and decreased disease incidence (HR 0.41, <i>p</i>=0.015) at 30 weeks. Flow cytometric analysis performed 5 weeks post treatment demonstrated reduced proliferation of conventional CD4⁺ T cells (0.87-fold, <i>p</i>=0.030) and CD8⁺ (0.78-fold, <i>p</i>=0.0018) effector memory T cells in spleens of anti-CD226-treated mice. Phenotyping of pancreatic Tregs revealed increased CD25 expression (2.05-fold, <i>p</i>=0.0073) and signal transducer and activator of transcription 5 (STAT5) phosphorylation (1.39-fold, <i>p</i>=0.0007) following anti-CD226, with splenic Tregs displaying augmented suppression of CD4⁺ responder T cells (Tresps) (1.49-fold, <i>p</i>=0.0008, 1:2 Treg:Tresp) in vitro<i>.</i> Anti-CD226-treated mice exhibited reduced frequencies of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive CD8⁺ T cells in the pancreas, using both ex vivo tetramer staining (0.50-fold, <i>p</i>=0.0317) and single-cell T cell receptor sequencing (0.61-fold, <i>p</i>=0.022) approaches. ⁵¹Cr-release assays demonstrated reduced cell-mediated lysis of beta cells (0.61-fold, <i>p</i>&lt;0.0001, 1:1 effector:target) by anti-CD226-treated autoreactive cytotoxic T lymphocytes.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>CD226 blockade reduces T cell cytotoxicity and improves Treg function, representing a targeted and rational approach for restoring immune regulation in type 1 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"53 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776373","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":"Up Front","authors":"","doi":"10.1007/s00125-024-06333-y","DOIUrl":"https://doi.org/10.1007/s00125-024-06333-y","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"19 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760479","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":"Metabolomics profiling in multi-ancestral individuals with type 2 diabetes in Singapore identified metabolites associated with renal function decline","authors":"Yuqing Chen, Federico Torta, Hiromi W. L. Koh, Peter I. Benke, Resham L. Gurung, Jian-Jun Liu, Keven Ang, Yi-Ming Shao, Gek Cher Chan, Jason Chon-Jun Choo, Jianhong Ching, Jean-Paul Kovalik, Tosha Kalhan, Rajkumar Dorajoo, Chiea Chuen Khor, Yun Li, Wern Ee Tang, Darren E. J. Seah, Charumathi Sabanayagam, Radoslaw M. Sobota, Kavita Venkataraman, Thomas Coffman, Markus R. Wenk, Xueling Sim, Su-Chi Lim, E Shyong Tai","doi":"10.1007/s00125-024-06324-z","DOIUrl":"https://doi.org/10.1007/s00125-024-06324-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>This study aims to explore the association between plasma metabolites and chronic kidney disease progression in individuals with type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We performed a comprehensive metabolomic analysis in a prospective cohort study of 5144 multi-ancestral individuals with type 2 diabetes in Singapore, using eGFR slope as the primary outcome of kidney function decline. In addition, we performed genome-wide association studies on metabolites to assess how these metabolites could be genetically influenced by metabolite quantitative trait loci and performed colocalisation analysis to identify genes affecting both metabolites and kidney function.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Elevated levels of 61 lipids with long unsaturated fatty acid chains such as phosphatidylethanolamines, triacylglycerols, diacylglycerols, ceramides and deoxysphingolipids were prospectively associated with more rapid kidney function decline. In addition, elevated levels of seven amino acids and three lipids in the plasma were associated with a slower decline in eGFR. We also identified 15 metabolite quantitative trait loci associated with these metabolites, within which variants near <i>TM6SF2</i>, <i>APOE</i> and <i>CPS1</i> could affect both metabolite levels and kidney functions.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Our study identified plasma metabolites associated with prospective renal function decline, offering insights into the underlying mechanism by which the metabolite abnormalities due to fatty acid oversupply might reflect impaired β-oxidation and associate with future chronic kidney disease progression in individuals with diabetes.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"12 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758488","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":"Evidence on the effectiveness and equity of population-based policies to reduce the burden of type 2 diabetes: a narrative review","authors":"Joreintje D. Mackenbach, Josine M. Stuber, Joline W. J. Beulens","doi":"10.1007/s00125-024-06330-1","DOIUrl":"https://doi.org/10.1007/s00125-024-06330-1","url":null,"abstract":"<p>There is increasing evidence for the effectiveness of population-based policies to reduce the burden of type 2 diabetes. Yet, there are concerns about the equity effects of some policies, whereby socioeconomically disadvantaged populations are not reached or are adversely affected. There is a lack of knowledge on the effectiveness and equity of policies that are both population based (i.e. targeting both at-risk and low-risk populations) and low agency (i.e. not requiring personal resources to benefit from the policy). In this narrative review, we selected 16 policies that were both population based and low agency and reviewed the evidence on their effectiveness and equity. Substantial evidence suggests that fruit and vegetable subsidies, unhealthy food taxes, mass media campaigns, and school nutrition and physical activity education are effective in promoting healthier lifestyle behaviours. Less evidence was available for mandatory food reformulation, reduced portion sizes, marketing restrictions and restriction of availability and promotion of unhealthy products, although the available evidence suggested that these policies were effective in reducing unhealthy food choices. Effects could rarely be quantified across different studies due to substantial heterogeneity. There is an overall lack of evidence on equity effects of population-based policies, although available studies mostly concluded that the policies had favourable equity effects, with the exception of food-labelling policies. Each of the policies is likely to have a relatively modest effect on population-level diabetes risks, which emphasises the importance of combining different policy measures. Future research should consider the type of evidence needed to demonstrate the real-world effectiveness and equity of population-based diabetes prevention policies.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"3 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758487","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":"A critique of measurement of defective insulin secretion and insulin sensitivity as a precision approach to gestational diabetes","authors":"Danielle L. Jones, Laura C. Kusinski, Clare Gillies, Claire L. Meek","doi":"10.1007/s00125-024-06334-x","DOIUrl":"https://doi.org/10.1007/s00125-024-06334-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency or both), and demonstrated associations with clinical outcomes. We aimed to assess whether using enhanced processing to determine indices of insulin secretion and sensitivity is analytically robust, reproducible in a different population, and useful diagnostically and prognostically in clinical practice.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A total of 1308 pregnant women with one or more risk factors for GDM who underwent a 75 g OGTT at one of nine hospital sites were recruited to this observational study. Specimens were collected for determination of glucose levels using standard and enhanced procedures, HbA_1c and insulin analysis. GDM diagnosis and management followed National Institute for Health and Care Excellence guidance. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA2-S &lt; 25th centile of the population with normal glucose tolerance [NGT]), insulin-insufficient GDM (HOMA2-B &lt; 25th centile), both or neither. We assessed associations with pregnancy outcomes using logistic regression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Using enhanced specimen handling, 1027/1308 (78.5%) women had NGT, with 281/1308 (21.5%) being classified as having GDM. Of this group, 135/281 (48.0%) had insulin-resistant GDM, 73/281 (26.0%) had insulin-insufficient GDM and 2/281 (0.7%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71 patients (25.3%) had GDM with both HOMA2-S and HOMA2-B ≥ 25th centile (GDM-neither). This novel subgroup appeared to be relatively insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinaemia, suggesting an isolated postprandial defect in insulin sensitivity that was not captured by HOMA2-B or HOMA2-S. Women within most GDM subgroups had comparable pregnancy outcomes to those of normoglycaemic women, and HOMA2-B and HOMA2-S were weak predictors of pregnancy outcomes. Maternal BMI predicted a similar number of outcomes to HOMA2-S, suggesting that there was no additional predictive value in adding HOMA2-S. Similar findings were obtained when using different indices and standard specimen handling techniques.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Precision categorisation of GDM using HOMA2-S and HOMA2-B does not provide useful diagnostic or prognostic information, but did distinguish a novel subgroup of patients with GDM, characterised by an isolated postprandial defect in insulin sensitivity.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"260 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758486","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":"The effect of vitamin D3 supplementation on the incidence of type 2 diabetes in healthy older adults not at high risk for diabetes (FIND): a randomised controlled trial","authors":"Jyrki K. Virtanen, Sari Hantunen, Niko Kallio, Christel Lamberg-Allardt, JoAnn E. Manson, Tarja Nurmi, Jussi Pihlajamäki, Matti Uusitupa, Ari Voutilainen, Tomi-Pekka Tuomainen","doi":"10.1007/s00125-024-06336-9","DOIUrl":"https://doi.org/10.1007/s00125-024-06336-9","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D&lt;sub&gt;3&lt;/sub&gt; supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged ≥60 years and ≥65 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications. The study had three arms: placebo, 1600 IU/day of vitamin D&lt;sub&gt;3&lt;/sub&gt; or 3200 IU/day of vitamin D&lt;sub&gt;3&lt;/sub&gt;. A non-study group statistician carried out sex-stratified simple randomisation in a 1:1:1 ratio, based on computerised random number generation. The participants, investigators and study staff were masked to group assignment. National health registries were used to collect event data. A representative subcohort of 505 participants had more detailed in-person investigations at months 0, 6, 12 and 24.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;During the mean follow-up of 4.2 years, there were 38 (5.0%), 31 (4.2%) and 36 (4.7%) type 2 diabetes events in the placebo (&lt;i&gt;n&lt;/i&gt;=760), 1600 IU/day vitamin D&lt;sub&gt;3&lt;/sub&gt; (&lt;i&gt;n&lt;/i&gt;=744; vs placebo: HR 0.81; 95% CI 0.50, 1.30) and 3200 IU/day vitamin D&lt;sub&gt;3&lt;/sub&gt; (&lt;i&gt;n&lt;/i&gt;=767; vs placebo: HR 0.92, 95% CI 0.58, 1.45) arms, respectively (&lt;i&gt;p&lt;/i&gt;-trend=0.73). When the two vitamin D&lt;sub&gt;3&lt;/sub&gt; arms were combined and compared with the placebo arm, the HR was 0.86 (95% CI 0.58, 1.29). In the analyses stratified by BMI (&lt;25 kg/m&lt;sup&gt;2&lt;/sup&gt; [&lt;i&gt;n&lt;/i&gt;=813, number of type 2 diabetes events=12], 25–30 kg/m&lt;sup&gt;2&lt;/sup&gt; [&lt;i&gt;n&lt;/i&gt;=1032, number of events=38], ≥30 kg/m&lt;sup&gt;2&lt;/sup&gt; [&lt;i&gt;n&lt;/i&gt;=422, number of events=54]), the HRs in the combined vitamin D&lt;sub&gt;3&lt;/sub&gt; arms vs the placebo were 0.43 (95% CI 0.14, 1.34), 0.97 (0.50, 1.91) and 1.00 (0.57, 1.75), respectively (&lt;i&gt;p&lt;/i&gt;-interaction &lt;0.001). In the subcohort, the mean (SD) baseline serum 25-hydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt; (25(OH)D&lt;sub&gt;3&lt;/sub&gt;) concentration was 74.5 (18.1) nmol/l. After 12 months, the concentrations were 72.6 (17.7), 99.3 (20.8) and 120.9 (22.1) nmol/l in the placebo, 1600 IU/day vitamin D&lt;sub&gt;3&lt;/sub&gt; and 3200 IU/day vitamin D&lt;sub&gt;3&lt;/sub&gt; arms, respectively. In the subcohort, no differences were observed in changes in plasma glucose or insulin concentrations, BMI or waist circumference during the 24 month follow-up (&lt;i&gt;p&lt;/i&gt; values ≥0.19).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusion/interpretation&lt;/h3&gt;&lt;p&gt;Among generally healthy older adults who are not at high risk for diabetes and who have serum 25(OH)D&lt;sub&gt;3&lt;/sub&gt; levels that are suffic","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"205 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758501","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}