Diabetologia最新文献

{"title":"Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.","authors":"Alfonso Galderisi, Emily K Sims, Carmella Evans-Molina, Alessandra Petrelli, David Cuthbertson, Brandon M Nathan, Heba M Ismail, Kevan C Herold, Antoinette Moran","doi":"10.1007/s00125-024-06323-0","DOIUrl":"10.1007/s00125-024-06323-0","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate.</p><p><strong>Methods: </strong>OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or <math><mo>≤</mo></math> 2 years). OMM metrics were also compared with the standard AUC C-peptide. Percentage changes in CD8⁺ T memory cell and programmed death-1 (PD-1) expression were evaluated in each group.</p><p><strong>Results: </strong>Baseline metabolic characteristics were similar between 28 placebo- and 39 teplizumab-treated participants. Over 12 months, insulin secretion declined in placebo-treated and rose in teplizumab-treated participants. Within groups, placebo slow-progressors (n=14) maintained insulin secretion and sensitivity, while both declined in placebo rapid-progressors (n=14). Teplizumab slow-progressors (n=28) maintained elevated insulin secretion, while teplizumab rapid-progressors (n=11) experienced mild metabolic decline. Compared with rapid-progressor groups, insulin clearance significantly decreased between baseline and 3, 6 and 12 months in the slow-progressor groups in both treatment arms. In aggregate, both higher baseline insulin secretion (p=0.027) and reduced 12 month insulin clearance (p=0.045) predicted slower progression. A >25% loss of insulin secretion at 3 months had specificity of 0.95 (95% CI 0.86, 1.00) to identify rapid-progressors and correctly classified the 2 year risk for progression in 92% of participants, with a sensitivity of 0.19 (95% CI 0.08, 0.30). OMM-estimated insulin secretion outperformed AUC C-peptide to differentiate groups by treatment or to predict progression. Metabolic changes were paralleled by relative frequency of change in PD-1⁺ CD8⁺ T effector memory cells.</p><p><strong>Conclusions/interpretation: </strong>OMM measures characterise the metabolic heterogeneity in stage 2 diabetes, identifying differences between rapid- and slow-progressors, and heterogeneous impacts of immunotherapy, suggesting the need to account for these differences when designing and interpreting clinical trials.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667393","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":"Simplified meal announcement study (SMASH) using hybrid closed-loop insulin delivery in youth and young adults with type 1 diabetes: a randomised controlled two-centre crossover trial.","authors":"Céline I Laesser, Camillo Piazza, Nina Schorno, Fabian Nick, Lum Kastrati, Thomas Zueger, Katharine Barnard-Kelly, Malgorzata E Wilinska, Christos T Nakas, Roman Hovorka, David Herzig, Daniel Konrad, Lia Bally","doi":"10.1007/s00125-024-06319-w","DOIUrl":"10.1007/s00125-024-06319-w","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>The majority of hybrid closed-loop systems still require carbohydrate counting (CC) but the evidence for its justification remains limited. Here, we evaluated glucose control with simplified meal announcement (SMA) vs CC in youth and young adults with type 1 diabetes using the mylife CamAPS FX system.</p><p><strong>Methods: </strong>We conducted a two-centre, randomised crossover, non-inferiority trial in two University Hospitals in Switzerland in 46 participants (aged 12-20 years) with type 1 diabetes using multiple daily injections (n=35), sensor-augmented pump (n=4) or hybrid closed-loop (n=7) therapy before enrolment. Participants underwent two 3 month periods with the mylife CamAPS FX system (YpsoPump, Dexcom G6) to compare SMA (individualised carbohydrate meal sizes) with CC, in a randomly assigned order using computer-generated sequences. The primary endpoint was the proportion of time glucose was in target range (3.9-10.0 mmol/l) with a non-inferiority margin of 5 percentage points. Secondary endpoints were other sensor glucose and insulin metrics, usability and safety endpoints.</p><p><strong>Results: </strong>Forty-three participants (18 women and girls) completed the trial. In the intention-to-treat analysis, time in range (mean±SD) was 69.9±12.4% with SMA and 70.7±13.0% with CC (estimated mean difference -0.6 percentage points [95% CI -2.4, 1.1], demonstrating non-inferiority). Time <3.9 mmol/l (median [IQR] 1.8 [1.2-2.2]% vs 1.9 [1.6-2.5]%) and >10.0 mmol/l (28.2±12.6% vs 27.2±13.4%) was similar between periods. Total daily insulin dose was higher with SMA (54.0±14.7 U vs 51.7±12.1 U, p=0.037). Three participants experienced serious adverse events, none of which were intervention-related.</p><p><strong>Conclusions/interpretation: </strong>Glucose control using the CamAPS FX algorithm with SMA was non-inferior to its use with CC in youth and young adults with type 1 diabetes.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05481034.</p><p><strong>Funding: </strong>The study was supported by the Swiss Diabetes Foundation and by a YTCR grant from the Bangerter-Rhyner Foundation and the Swiss Academy of Medical Sciences. Dexcom and Ypsomed provided product support.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667392","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":"Prediabetes is associated with elevated risk of clinical outcomes even without progression to diabetes","authors":"Mary R. Rooney, Amelia S. Wallace, Justin B. Echouffo Tcheugui, Michael Fang, Jiaqi Hu, Pamela L. Lutsey, Morgan E. Grams, Josef Coresh, Elizabeth Selvin","doi":"10.1007/s00125-024-06315-0","DOIUrl":"https://doi.org/10.1007/s00125-024-06315-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Prediabetes (HbA_1c 39–47 mmol/mol [5.7–6.4%] or fasting glucose 5.6–6.9 mmol/l) is associated with elevated risks of microvascular and macrovascular complications. It is unknown to what extent these risks in prediabetes remain after accounting for progression to diabetes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46–70 years, ~55% women, ~20% Black adults) without diabetes at baseline (1990–1992), we used Cox regression to characterise age- and sex-adjusted associations of prediabetes with ~30 year incidence of complications (composite and separately), including atherosclerotic CVD (ASCVD), heart failure, chronic kidney disease (CKD) and all-cause mortality before and after accounting for intervening incidence of diabetes, modelled as a time-varying variable. We calculated the excess risk of complications in prediabetes remaining after accounting for progression to diabetes.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of the 60% of adults with prediabetes at baseline, ~30% progressed to diabetes (median time to diabetes, 7 years). Over the maximum follow-up of ~30 years, there were 7069 events (1937 ASCVD, 2109 heart failure, 3288 CKD and 4785 deaths). Prediabetes was modestly associated with risk of any complication (HR 1.21 [95% CI 1.15, 1.27]) vs normoglycaemia. This association remained significant after accounting for progression to diabetes (HR 1.18 [95% CI 1.12, 1.24]) with 85% (95% CI 75, 94%) of the excess risk of any complication in prediabetes remaining. Results were similar for the individual complications.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Progression to diabetes explained less than one-quarter of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to the risk of clinical outcomes even without progression to diabetes.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"23 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599736","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":"Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes","authors":"Gechang Yu, Claudia H. T. Tam, Cadmon K. P. Lim, Mai Shi, Eric S. H. Lau, Risa Ozaki, Heung-man Lee, Alex C. W. Ng, Yong Hou, Baoqi Fan, Chuiguo Huang, Hongjiang Wu, Aimin Yang, Hoi Man Cheung, Ka Fai Lee, Shing Chung Siu, Grace Hui, Chiu Chi Tsang, Kam Piu Lau, Jenny Y. Y. Leung, Elaine Y. N. Cheung, Man Wo Tsang, Grace Kam, Ip Tim Lau, June K. Y. Li, Vincent T. F. Yeung, Emmy Lau, Stanley Lo, Samuel Fung, Yuk Lun Cheng, Cheuk Chun Szeto, Elaine Chow, Alice P. S. Kong, Wing Hung Tam, Andrea O. Y. Luk, Michael N. Weedon, Wing-yee So, Juliana C. N. Chan, Richard A. Oram, Ronald C. W. Ma","doi":"10.1007/s00125-024-06309-y","DOIUrl":"https://doi.org/10.1007/s00125-024-06309-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The ‘total’ type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (<i>n</i>=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA_1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], <i>p</i>&lt;0.0001), end-stage renal disease (1.10 [1.04, 1.16], <i>p</i>=0.0007) and CVD (1.10 [1.05, 1.16], <i>p</i>&lt;0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], <i>p</i>=0.0001) and heart failure (0.83 [0.73, 0.93], <i>p</i>=0.0011). Major findings remained significant after adjusting for a set of clinical variables.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"95 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599704","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 metabolic and circadian signatures of gestational diabetes in the postpartum period characterised using multiple wearable devices","authors":"Nicholas E. Phillips, Julie Mareschal, Andrew D. Biancolin, Flore Sinturel, Sylvie Umwali, Stéphanie Blanc, Alexandra Hemmer, Felix Naef, Marcel Salathé, Charna Dibner, Jardena J. Puder, Tinh-Hai Collet","doi":"10.1007/s00125-024-06318-x","DOIUrl":"https://doi.org/10.1007/s00125-024-06318-x","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Gestational diabetes mellitus (GDM) affects 14% of all pregnancies worldwide and is associated with cardiometabolic risk. We aimed to exploit high-resolution wearable device time-series data to create a fine-grained physiological characterisation of the postpartum GDM state in free-living conditions, including clinical variables, daily glucose dynamics, food and drink consumption, physical activity, sleep patterns and heart rate.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;In a prospective observational study, we employed continuous glucose monitors (CGMs), a smartphone food diary, triaxial accelerometers and heart rate and heart rate variability monitors over a 2 week period to compare women who had GDM in the previous pregnancy (GDM group) and women who had a pregnancy with normal glucose metabolism (non-GDM group) at 1–2 months after delivery (baseline) and 6 months later (follow-up). We integrated CGM data with ingestion events recorded with the smartphone app MyFoodRepo to quantify the rapidity of returning to preprandial glucose levels after meal consumption. We inferred the properties of the underlying 24 h rhythm in the baseline glucose. Aggregating the baseline and follow-up data in a linear mixed model, we quantified the relationships between glycaemic variables and wearable device-derived markers of circadian timing.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Compared with the non-GDM group (&lt;i&gt;n&lt;/i&gt;=15), the GDM group (&lt;i&gt;n&lt;/i&gt;=22, including five with prediabetes defined based on fasting plasma glucose [5.6–6.9 mmol/l (100–125 mg/dl)] and/or HbA&lt;sub&gt;1c&lt;/sub&gt; [39–47 mmol/mol (5.7–6.4%)]) had a higher BMI, HbA&lt;sub&gt;1c&lt;/sub&gt; and mean amplitude of glycaemic excursion at baseline (all &lt;i&gt;p&lt;/i&gt;≤0.05). Integrating CGM data and ingestion events showed that the GDM group had a slower postprandial glucose decrease (&lt;i&gt;p&lt;/i&gt;=0.01) despite having a lower proportion of carbohydrate intake, similar mean glucose levels and a reduced amplitude of the underlying glucose 24 h rhythm (&lt;i&gt;p&lt;/i&gt;=0.005). Differences in CGM-derived variables persisted when the five women with prediabetes were removed from the comparison. Longitudinal analysis from baseline to follow-up showed a significant increase in fasting plasma glucose across both groups. The CGM-derived metrics showed no differences from baseline to follow-up. Late circadian timing (i.e. sleep midpoint, eating midpoint and peak time of heart rate) was correlated with higher fasting plasma glucose and reduced amplitudes of the underlying glucose 24 h rhythm (all &lt;i&gt;p&lt;/i&gt;≤0.05).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions/interpretation&lt;/h3&gt;&lt;p&gt;We reveal GDM-related postpartum differences in glucose variability and 24 h rhythms, even among women clinically considered to be normoglycaemic. Our results provide a rationale for future interventions aimed at improving glucose variability and encouraging earlier daily beh","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"60 3 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599735","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 WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome","authors":"Raniero Chimienti, Silvia Torchio, Gabriel Siracusano, Valentina Zamarian, Laura Monaco, Marta Tiffany Lombardo, Silvia Pellegrini, Fabio Manenti, Federica Cuozzo, Greta Rossi, Paola Carrera, Valeria Sordi, Vania Broccoli, Riccardo Bonfanti, Giorgio Casari, Giulio Frontino, Lorenzo Piemonti","doi":"10.1007/s00125-024-06307-0","DOIUrl":"https://doi.org/10.1007/s00125-024-06307-0","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Wolfram syndrome 1 (WS1) is an inherited condition mainly manifesting in childhood-onset diabetes mellitus and progressive optic nerve atrophy. The causative gene, &lt;i&gt;WFS1&lt;/i&gt;, encodes wolframin, a master regulator of several cellular responses, and the gene’s mutations associate with clinical variability. Indeed, nonsense/frameshift variants correlate with more severe symptoms than missense/in-frame variants. As achieving a genotype–phenotype correlation is crucial for dealing with disease outcome, works investigating the impact of transcriptional and translational landscapes stemming from such mutations are needed. Therefore, we sought to elucidate the molecular determinants behind the pathophysiological alterations in a WS1 patient carrying compound heterozygous mutations in &lt;i&gt;WFS1&lt;/i&gt;: c.316-1G&gt;A, affecting the acceptor splice site (ASS) upstream of exon 4; and c.757A&gt;T, introducing a premature termination codon (PTC) in exon 7.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;Bioinformatic analysis was carried out to infer the alternative splicing events occurring after disruption of ASS, followed by RNA-seq and PCR to validate the transcriptional landscape. Patient-derived induced pluripotent stem cells (iPSCs) were used as an in vitro model of WS1 and to investigate the &lt;i&gt;WFS1&lt;/i&gt; alternative splicing isoforms in pancreatic beta cells. CRISPR/Cas9 technology was employed to correct ASS mutation and generate a syngeneic control for the endoplasmic reticulum stress induction and immunotoxicity assays.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;We showed that patient-derived iPSCs retained the ability to differentiate into pancreatic beta cells. We demonstrated that the allele carrying the ASS mutation c.316-1G&gt;A originates two PTC-containing alternative splicing transcripts (c.316del and c.316–460del), and two open reading frame-conserving mRNAs (c.271–513del and c.316–456del) leading to N-terminally truncated polypeptides. By retaining the C-terminal domain, these isoforms sustained the endoplasmic reticulum stress response in beta cells. Otherwise, PTC-carrying transcripts were regulated by the nonsense-mediated decay (NMD) in basal conditions. Exposure to cell stress inducers and proinflammatory cytokines affected expression levels of the NMD-related gene &lt;i&gt;SMG7&lt;/i&gt; (&gt;twofold decrease; &lt;i&gt;p&lt;/i&gt;&lt;0.001) without eliciting a robust unfolded protein response in WFS1 beta cells. This resulted in a dramatic accumulation of the PTC-containing isoforms c.316del (&gt;100-fold increase over basal; &lt;i&gt;p&lt;/i&gt;&lt;0.001) and c.316–460del (&gt;20-fold increase over basal; &lt;i&gt;p&lt;/i&gt;&lt;0.001), predisposing affected beta cells to undergo apoptosis. Cas9-mediated recovery of ASS retrieved the canonical transcriptional landscape, rescuing the normal phenotype in patient-derived beta cells.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions/interpretation&lt;/h3&gt;&lt;p&gt;Thi","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"148 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597073","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":"Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013–2019","authors":"Eric Wang, Elisabetta Patorno, Farzin Khosrow-Khavar, Stephen Crystal, Chintan V. Dave","doi":"10.1007/s00125-024-06321-2","DOIUrl":"https://doi.org/10.1007/s00125-024-06321-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>The aim of this study was to investigate racial and ethnic disparities in the use of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) among older adults with type 2 diabetes and cardiorenal conditions.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Using Medicare fee-for-service data (2013–2019), this retrospective cohort study identified older adults (≥65 years) with type 2 diabetes initiating second-line therapies (SGLT2is, GLP1-RAs, dipeptidyl peptidase-4 inhibitors [DPP4is] and sulfonylureas [SUs]) with (1) heart failure (HF), (2) atherosclerotic cardiovascular disease (ASCVD), (3) chronic kidney disease (CKD) and (4) no recorded cardiorenal conditions. Participants were classified as non-Hispanic White, non-Hispanic Black and Hispanic. Multinomial regressions, adjusting for sociodemographic, clinical and county-level characteristics, were used to model the odds of initiating SGLT2is or GLP-1RAs within each cohort.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Black participants with HF, ASCVD, CKD or no recorded cardiorenal conditions had 35% (adjusted OR 0.65 [95% CI 0.61, 0.68]), 33% (0.67 [0.64, 0.69]), 32% (0.68 [0.64, 0.72]) and 24% (0.76 [0.74, 0.79]) lower odds of initiating SGLT2is, respectively, than White participants. Disparities ameliorated from 50–60% lower odds in 2013 to 17–18% in 2019. Similar patterns were observed for GLP-1RA uptake among Black participants. By contrast, Hispanic participants had similar odds of SGLT2i initiation in the HF and CKD cohorts as White participants, but 6% (0.94 [0.91, 0.98]) lower odds in the ASCVD cohort. Notable disparities for Hispanic participants compared with White participants were observed for GLP-1RA uptake in the HF, ASCVD, CKD and no cardiorenal conditions cohorts: 11% (0.89 [0.84, 0.94]), 16% (0.84 [0.81, 0.87]), 16% (0.84 [0.80, 0.89]) and 25% (0.75 [0.72, 0.78]) lower odds, respectively. Participants had greater odds than White participants of initiating DPP4is, which confer no cardiorenal benefits, across all cohorts (HF 1.25 [1.19, 1.31]; ASCVD 1.36 [1.32, 1.40]; CKD 1.32 [1.26, 1.38). Adjustment for social determinants of health did not meaningfully change the study findings.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Compared with White participants, disparities in the uptake of SGLT2is were evident for Black participants, and in the uptake of GLP-1RAs for both Black and Hispanic participants. This study highlights how type 2 diabetes management is evolving, while underscoring historical imbalances that have shown signs of abatement.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"244 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597075","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":"Diabetes knowledge and behaviour: a cross-sectional study of Jordanian adults.","authors":"Rula A Amr, Ahmed M Al-Smadi, Rand T Akasheh","doi":"10.1007/s00125-024-06304-3","DOIUrl":"https://doi.org/10.1007/s00125-024-06304-3","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Diabetes mellitus is a significant global health concern that is projected to affect 7.7% of the global population by 2030. Understanding factors that influence diabetes knowledge and management adherence is crucial for effective diabetes mellitus management and prevention. This study investigates the relationships between demographic and clinical factors and their impact on diabetes knowledge and behaviour, as well as the potential influence of diabetes knowledge on management behaviours.</p><p><strong>Methods: </strong>The study comprised a cross-sectional survey of 1050 adults, collecting data on age, sex, marital status, education, employment, hypertension, dyslipidaemia (any lipid imbalance, such as high cholesterol, high LDL-cholesterol or low HDL-cholesterol), smoking and diabetes status. Two multiple linear regression models were used to identify factors associated with diabetes knowledge and behaviour, and a simple linear regression model was used to assess the relationship between knowledge and behaviour.</p><p><strong>Results: </strong>Significant associations were found between diabetes knowledge and the following factors: age (44.32 ± 9.53 for ≥50 years vs 39.73 ± 9.95 for 18 to <25 years; p<0.0001), sex (49.00 ± 12.35 for women vs 45.09 ± 13.27 for men; p<0.0001), marital status (50.92 ± 11.69 for married vs 45.39 ± 13.10 for single; p<0.0001), smoking status (45.78 ± 13.22 for smokers vs 48.22 ± 12.15 for non-smokers; p=0.003), hypertension (46.46 ± 13.11 for present vs 47.31 ± 12.87 for absent; p=0.007) and diabetes status (69.49 ± 17.35 for present vs 62.76 ± 16.88 for absent; p<0.001). Behaviour scores correlated similarly with these factors except for diabetes and smoking status. The adjusted simple linear regression model revealed that diabetes knowledge was significantly associated with better management behaviours (coefficient=0.0794, p<0.001) after adjusting for demographic and clinical factors.</p><p><strong>Conclusions/interpretation: </strong>This study highlights the importance of demographic and clinical factors in the context of diabetes knowledge and behaviours, underscoring the need for targeted educational and preventive programmes to improve diabetes management, especially in vulnerable populations. Additionally, the strong association between diabetes knowledge and management behaviours supports a knowledge-attitude-behaviour (KAB) model of diabetes management.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589732","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":"Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers","authors":"Nick S. R. Lan, Jonathan Hiew, Ivana Ferreira, J. Carsten Ritter, Laurens Manning, P. Gerry Fegan, Girish Dwivedi, Emma J. Hamilton","doi":"10.1007/s00125-024-06316-z","DOIUrl":"https://doi.org/10.1007/s00125-024-06316-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D−/I−), not deep but infected (D−/I+), deep with no infection (D+/I−) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of 513 patients, 241 (47.0%) were in the D−/I− group, 110 (21.4%) were in the D−/I+ group, 35 (6.8%) were in the D+/I− group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220–551) and 404 days (IQR 228–576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; <i>p</i>&lt;0.001) and MACE alone (13.5% vs 5.1%; <i>p</i>=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D−/I− 7.9%; D−/I+ 15.5%; D+/I− 14.3%; D+/I+ 26.8%; <i>p</i>&lt;0.001), as was MACE alone (D−/I− 5.0%; D−/I+ 10.9%; D+/I− 5.7%; D+/I+ 15.7%; <i>p</i>=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"18 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594916","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":"NT-proBNP improves prediction of cardiorenal complications in type 2 diabetes: the Hong Kong Diabetes Biobank","authors":"Ronald C. W. Ma, Claudia H. T. Tam, Yong Hou, Eric S. H. Lau, Risa Ozaki, Juliana N. M. Lui, Elaine Chow, Alice P. S. Kong, Chuiguo Huang, Alex C. W. Ng, Erik G. Fung, Andrea O. Y. Luk, Wing Yee So, Cadmon K. P. Lim, Juliana C. N. Chan","doi":"10.1007/s00125-024-06299-x","DOIUrl":"https://doi.org/10.1007/s00125-024-06299-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>N-terminal pro B-type natriuretic peptide (NT-proBNP) is a natriuretic peptide that is strongly associated with congestive heart failure (CHF). The utility of NT-proBNP for prediction of cardiovascular events and renal endpoints, compared with clinical risk factors, has not been evaluated in detail. We hypothesise that NT-proBNP can improve risk stratification and prediction of cardiorenal events in type 2 diabetes, beyond that provided by clinical risk factors.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>NT-proBNP was measured in 1993 samples from the Hong Kong Diabetes Biobank, a multicentre prospective diabetes cohort and biobank. A cut-off of ≥125 pg/ml was used to define elevated NT-proBNP. Associations between elevated NT-proBNP and incident cardiovascular and renal endpoints were examined using Cox regression, adjusted for sex, age and duration of diabetes, as well as other covariates. Prognostic and incremental predictive values of NT-proBNP in diabetes cardiorenal complications, compared with those of the Joint Asia Diabetes Evaluation risk equations for CHD, CHF and kidney failure, were evaluated using the concordance index (C index), net reclassification improvement index, integrated discrimination improvement index and relative integrated discrimination improvement index.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 24.7% of participants had elevated NT-proBNP. Participants with elevated NT-proBNP at baseline had a more adverse cardiometabolic profile, with 2–4-fold higher frequency of complications at baseline. Adjusting for age at baseline, sex and duration of diabetes, elevated NT-proBNP was associated with incident atrial fibrillation (HR 4.64 [95% CI 2.44, 8.85]), CHD (HR 4.21 [2.46, 7.21]), CVD (HR 3.32 [2.20, 5.01]) and CHF (HR 4.18 [2.18, 8.03]; all <i>p</i>&lt;0.001). All these associations remained significant after further adjustment for additional covariates. Elevated NT-proBNP had good discriminative ability for various cardiorenal endpoints, with C index of 0.83 (95% CI 0.76, 0.90) for CHD, 0.88 (0.81, 0.94) for atrial fibrillation, 0.89 (0.83, 0.95) for CHF, 0.81 (0.77, 0.84) for 40% drop in eGFR and 0.88 (0.84, 0.92) for kidney failure. Models incorporating NT-proBNP had improved prediction compared with established clinical risk models. Sensitivity analyses including alternative cut-off of NT-proBNP, as well as use of other risk engines of CHD, yielded similar results.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>NT-proBNP demonstrated a promising ability to serve as a prognostic marker for a variety of cardiorenal complications in type 2 diabetes. Considering NT-proBNP in clinical assessments could potentially help identify high-risk individuals who may benefit from more intensive therapies.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"9 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594912","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}