Diabetologia最新文献

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Prediabetes is associated with elevated risk of clinical outcomes even without progression to diabetes 即使没有发展为糖尿病,糖尿病前期也与临床结果风险升高有关
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-12 DOI: 10.1007/s00125-024-06315-0
Mary R. Rooney, Amelia S. Wallace, Justin B. Echouffo Tcheugui, Michael Fang, Jiaqi Hu, Pamela L. Lutsey, Morgan E. Grams, Josef Coresh, Elizabeth Selvin
{"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<sub>1c</sub> 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":null,"pages":null},"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}
引用次数: 0
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 2型糖尿病路径特异性多基因风险评分阐明了18 217名中国2型糖尿病患者在临床表现、疾病进展和糖尿病并发症方面的异质性
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-12 DOI: 10.1007/s00125-024-06309-y
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
{"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<sub>1c</sub> 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":null,"pages":null},"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}
引用次数: 0
The metabolic and circadian signatures of gestational diabetes in the postpartum period characterised using multiple wearable devices 使用多种可穿戴设备描述产后妊娠糖尿病的代谢和昼夜节律特征
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-12 DOI: 10.1007/s00125-024-06318-x
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
{"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":null,"pages":null},"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}
引用次数: 0
A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome 破坏接受剪接位点的 WFS1 变体揭示了替代剪接对沃尔夫拉姆综合征患者β细胞凋亡的影响
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-09 DOI: 10.1007/s00125-024-06307-0
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
{"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":null,"pages":null},"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}
引用次数: 0
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 2013-2019年2型糖尿病合并心力衰竭、动脉粥样硬化性心血管疾病和慢性肾病的医疗保险受益人在服用SGLT2is和GLP-1RAs方面的种族和民族差异
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-08 DOI: 10.1007/s00125-024-06321-2
Eric Wang, Elisabetta Patorno, Farzin Khosrow-Khavar, Stephen Crystal, Chintan V. Dave
{"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":null,"pages":null},"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}
引用次数: 0
Diabetes knowledge and behaviour: a cross-sectional study of Jordanian adults. 糖尿病知识与行为:对约旦成年人的横断面研究。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06304-3
Rula A Amr, Ahmed M Al-Smadi, Rand T Akasheh
{"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":null,"pages":null},"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}
引用次数: 0
Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers 深层感染性糖尿病足溃疡患者发生重大不良心血管事件的风险增加
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06316-z
Nick S. R. Lan, Jonathan Hiew, Ivana Ferreira, J. Carsten Ritter, Laurens Manning, P. Gerry Fegan, Girish Dwivedi, Emma J. Hamilton
{"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":null,"pages":null},"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}
引用次数: 0
NT-proBNP improves prediction of cardiorenal complications in type 2 diabetes: the Hong Kong Diabetes Biobank NT-proBNP可提高对2型糖尿病心肾并发症的预测能力:香港糖尿病生物数据库
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06299-x
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
{"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":null,"pages":null},"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}
引用次数: 0
Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models 非β胰岛细胞转录组异质性与小鼠模型中 2 型糖尿病的发生有关
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06301-6
Pascal Gottmann, Thilo Speckmann, Mandy Stadion, Prateek Chawla, Judith Saurenbach, Nikolay Ninov, Heiko Lickert, Annette Schürmann
{"title":"Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models","authors":"Pascal Gottmann, Thilo Speckmann, Mandy Stadion, Prateek Chawla, Judith Saurenbach, Nikolay Ninov, Heiko Lickert, Annette Schürmann","doi":"10.1007/s00125-024-06301-6","DOIUrl":"https://doi.org/10.1007/s00125-024-06301-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>The aim of this work was to understand the role of non-beta cells in pancreatic islets at early stages of type 2 diabetes pathogenesis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Specific clustering was employed to single-cell transcriptome data from islet cells of obese mouse strains differing in their diabetes susceptibility (diabetes-resistant B6.V.<i>Lep</i><sup>ob/ob</sup> [OB] and diabetes-susceptible New Zealand Obese [NZO] mice) on a diabetogenic diet.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Refined clustering analysis revealed several heterogeneous subpopulations for alpha cells, delta cells and macrophages, of which 133 mapped to human diabetes genes identified by genome-wide association studies. Importantly, a similar non-beta cell heterogeneity was found in a dataset of human islets from donors at different stages of type 2 diabetes. The predominant alpha cell cluster in NZO mice displayed signs of cellular stress and lower mitochondrial capacity (97 differentially expressed genes [DEGs]), whereas delta cells from these mice exhibited higher expression levels of maturation marker genes (<i>Hhex</i> and <i>Sst</i>) but lower somatostatin secretion than OB mice (184 DEGs). Furthermore, a cluster of macrophages was almost twice as abundant in islets of OB mice, and displayed extensive cell–cell communication with beta cells of OB mice. Treatment of beta cells with IL-15, predicted to be released by macrophages, activated signal transducer and activator of transcription (STAT3), which may mediate anti-apoptotic effects. Similar to mice, humans without diabetes possess a greater number of macrophages than those with prediabetes (39 mmol/mol [5.7%] &lt; HbA<sub>1c</sub> &lt; 46 mmol/mol [6.4%]) and diabetes.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Our study indicates that the transcriptional heterogeneity of non-beta cells has an impact on intra-islet crosstalk and participates in beta cell (dys)function.</p><h3 data-test=\"abstract-sub-heading\">Data availability</h3><p>scRNA-seq data from the previous study are available in gene expression omnibus under gene accession number GSE159211 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159211).</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594913","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}
引用次数: 0
Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of type 1 diabetes β细胞胞外囊泡 PD-L1 是 CD8+ T 细胞活性的新型调节因子和 1 型糖尿病演变过程中的生物标记物
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06313-2
Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans-Molina, Jon D. Piganelli, Decio L. Eizirik, Raghavendra G. Mirmira, Emily K. Sims
{"title":"Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of type 1 diabetes","authors":"Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans-Molina, Jon D. Piganelli, Decio L. Eizirik, Raghavendra G. Mirmira, Emily K. Sims","doi":"10.1007/s00125-024-06313-2","DOIUrl":"https://doi.org/10.1007/s00125-024-06313-2","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;Beta cell lines and human islets were treated with proinflammatory cytokines to model the proinflammatory type 1 diabetes microenvironment. EVs were isolated using ultracentrifugation or size exclusion chromatography and analysed via immunoblot, flow cytometry and ELISA. EV PD-L1 binding to PD-1 was assessed using a competitive binding assay and in vitro functional assays testing the ability of EV PD-L1 to inhibit NOD CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Plasma EV and soluble PD-L1 were assayed in the plasma of islet autoantibody-positive (Ab&lt;sup&gt;+&lt;/sup&gt;) individuals or individuals with recent-onset type 1 diabetes and compared with levels in non-diabetic control individuals.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;PD-L1 protein co-localised with tetraspanin-associated proteins intracellularly and was detected on the surface of beta cell EVs. Treatment with IFN-α or IFN-γ for 24 h induced a twofold increase in EV PD-L1 cargo without a corresponding increase in the number of EVs. IFN exposure predominantly increased PD-L1 expression on the surface of beta cell EVs and beta cell EV PD-L1 showed a dose-dependent capacity to bind PD-1. Functional experiments demonstrated specific effects of beta cell EV PD-L1 to suppress proliferation and cytotoxicity of murine CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Plasma EV PD-L1 levels were increased in Ab&lt;sup&gt;+&lt;/sup&gt;individuals, particularly in those positive for a single autoantibody. Additionally, in Ab&lt;sup&gt;+&lt;/sup&gt; individuals or those who had type 1 diabetes, but not in control individuals, plasma EV PD-L1 positively correlated with circulating C-peptide, suggesting that higher EV PD-L1 could be protective for residual beta cell function.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions/interpretation&lt;/h3&gt;&lt;p&gt;IFN exposure increases PD-L1 on the beta cell EV surface. Beta cell EV PD-L1 binds PD1 and inhibits CD8&lt;sup&gt;+&lt;/sup&gt; T cell proliferation and cytotoxicity. Circulating EV PD-L1 is higher in Ab&lt;sup&gt;+&lt;/sup&gt; individuals than in control individuals. Circulating EV PD-L1 levels correlate with residual C-peptide at different stages in type 1 diabetes progression. These findings suggest that EV PD-L1 could contribute to heterogeneity in type 1 diabetes progression and residual beta cell function and raise the possibility that EV PD-L1 could be exploited as a means to inhibit ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594915","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}
引用次数: 0
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