Diabetes Care最新文献

{"title":"Subtypes of Gestational Diabetes Mellitus Are Differentially Associated With Newborn and Childhood Metabolic Outcomes","authors":"Meredith E. Osmulski, Yuanzhi Yu, Alan Kuang, Jami L. Josefson, Marie-France Hivert, Denise M. Scholtens, William L. Lowe","doi":"10.2337/dc24-1735","DOIUrl":"https://doi.org/10.2337/dc24-1735","url":null,"abstract":"OBJECTIVE Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes. RESEARCH DESIGN AND METHODS Newborn and child (age 11–14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) and Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion), or mixed-defect GDM (both <25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes. RESULTS Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds >90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127–2.08). The risk of child-impaired glucose tolerance was higher with insulin-resistant (OR 2.21, 95% CI 1.50–3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47–6.19). CONCLUSIONS GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"75 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939855","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":"Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes","authors":"Richeek Pradhan, Hui Yin, Sally Lu, Giada Sebastiani, Oriana Yu, Samy Suissa, Laurent Azoulay","doi":"10.2337/dc24-1903","DOIUrl":"https://doi.org/10.2337/dc24-1903","url":null,"abstract":"OBJECTIVE To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With an active comparator, new-user approach, we conducted a cohort study using the U.K. Clinical Practice Research Datalink linked with hospital and national statistics databases. Cox proportional hazards models using propensity score fine stratification weighting were used to calculate hazard ratios (HRs) and 95% CIs for cirrhosis (primary outcome) and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes). RESULTS In the first cohort comparing 25,516 patients starting GLP-1RAs and 186,752 starting DPP-4 inhibitors, GLP-1RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68–1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46–0.90), as also decompensated cirrhosis (HR 0.74, 95% CI 0.54–1.00), but not with a lower risk of hepatocellular carcinoma or liver-related mortality. CONCLUSIONS In patients with type 2 diabetes in the U.K., GLP-1RAs were not associated with a lower risk of cirrhosis compared with DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared with DPP-4 inhibitors.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"479 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936933","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":"Plasma Lipid Metabolites, Clinical Glycemic Predictors, and Incident Type 2 Diabetes","authors":"Arjana Begzati, Karla P. Godinez-Macias, Tao Long, Jeramie D. Watrous, Rafael Moranchel, Edward D. Kantz, Jaakko Tuomilehto, Aki S. Havulinna, Teemu J. Niiranen, Pekka Jousilahti, Veikko Salomaa, Bing Yu, Faye Norby, Casey M. Rebholz, Elizabeth Selvin, Elizabeth A. Winzeler, Susan Cheng, Mona Alotaibi, Ravi Goyal, Trey Ideker, Mohit Jain, Amit R. Majithia","doi":"10.2337/dc24-2266","DOIUrl":"https://doi.org/10.2337/dc24-2266","url":null,"abstract":"OBJECTIVE Plasma metabolite profiling has uncovered several nonglycemic markers of incident type 2 diabetes (T2D). We investigated whether such biomarkers provide information about specific aspects of T2D etiology, such as impaired fasting glucose and impaired glucose tolerance, and whether their association with T2D risk varies by race. RESEARCH DESIGN AND METHODS Untargeted plasma metabolite profiling was performed of participants in the FINRISK 2002 cohort (n = 7,564). Cox regression modeling was conducted to identify metabolites associated with incident T2D during 14 years of follow-up. Metabolites were clustered into pathways using Gaussian graphical modeling. Clusters enriched for T2D biomarkers were further examined for covariation with fasting plasma glucose (FPG), 2-h postchallenge plasma glucose (2hPG), HbA1c, or fasting insulin. Validation analyses and tests of interaction with race were performed in the Atherosclerosis Risk in Communities study. RESULTS Two clusters of metabolites, representing diacylglycerols (DAGs) and phosphatidylcholines (PCs), contained the largest number of metabolite associations with incident T2D. DAGs associated with increased T2D incidence (hazard ratio [HR] 1.22; 95% CI 1.14–1.30) independent of FPG, HbA1c, and fasting insulin, but not 2hPG. PCs were inversely associated with T2D risk (HR 0.78; 95% CI 0.71–0.85) independent of FPG, 2hPG, HbA1c, and fasting insulin. No significant interaction between DAGs or PCs and race was observed. CONCLUSIONS Fasting DAGs may capture information regarding T2D risk similar to that represented by 2hPG; PCs may capture aspects of T2D etiology that differ from those represented by conventional biomarkers. The direction of effect and strength of DAG and PC associations with incident T2D are similar across European and African Americans.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"35 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935024","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, Subclinical Myocardial Injury or Stress and Risk of Heart Failure Subtypes: The Jackson Heart Study","authors":"Arnaud D. Kaze, Alain G. Bertoni, Ervin R. Fox, Michael E. Hall, Robert J. Mentz, Jarett D. Berry, Justin B. Echouffo-Tcheugui","doi":"10.2337/dc24-0654","DOIUrl":"https://doi.org/10.2337/dc24-0654","url":null,"abstract":"OBJECTIVE To assess the extent to which the concomitant presence of subclinical myocardial injury or stress and diabetes affects the risk of heart failure (HF) subtypes. RESEARCH DESIGN AND METHODS The Jackson Heart Study included Black adults, categorized based on diabetes status, high-sensitivity cardiac troponin I (hs-cTnI), and brain natriuretic peptide (BNP) levels. Subclinical myocardial injury was defined as hs-cTnI ≥4 ng/L in women and ≥6 ng/L in men, and subclinical myocardial stress as BNP ≥35 pg/mL. The study outcomes included incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). RESULTS Among 3,484 participants (mean age 54.6 years, 63.2% women, 22.3% with diabetes, 26.4% with subclinical myocardial injury, 9.4% with subclinical myocardial stress), 306 developed HF (151 HFpEF and 139 HFrEF) over 12 years. Compared with individuals with no diabetes and no subclinical myocardial injury at recruitment, participants with diabetes and subclinical myocardial injury had a higher HF risk (hazard ratio [HR] 3.84, 95% CI 2.60–5.66), HFpEF (HR 3.68, 95% CI 2.13–6.36), and HFrEF (HR 4.26, 95% CI 2.40–7.53). The HRs associated with the presence of diabetes and subclinical myocardial stress versus their joint absence were 4.03 (95% CI 2.50–6.51), 5.71 (95% CI 3.11–10.47), and 2.13 (95% CI 0.88–5.17) for HF, HFpEF, and HFrEF, respectively. There was no significant diabetes status and cardiac biomarkers interaction. CONCLUSIONS Both diabetes and subclinical myocardial damage significantly increase the risk of all HF types among Black individuals.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"20 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935022","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":"Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study","authors":"Hancheng Yu, Jijuan Zhang, Frank Qian, Pang Yao, Kun Xu, Ping Wu, Rui Li, Zixin Qiu, Ruyi Li, Kai Zhu, Lin Li, Tingting Geng, Xuefeng Yu, Danpei Li, Yunfei Liao, An Pan, Gang Liu","doi":"10.2337/dc24-1696","DOIUrl":"https://doi.org/10.2337/dc24-1696","url":null,"abstract":"OBJECTIVE Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction. RESEARCH DESIGN AND METHODS This cohort study included 1,859 individuals with T2D from the UK Biobank. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident PAD. Proteins were further selected as predictors using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement. RESULTS Over a median follow-up of 13.2 years, 157 incident PAD cases occurred. We observed 463 proteins associated with PAD risk, primarily involved in pathways related to signal transduction, inflammatory response, plasma membrane, protein binding, and cytokine-cytokine receptor interactions. Ranking by P values, the top five proteins associated with increased PAD risk included EDA2R, ADM, NPPB, CD302, and NPC2, while BCAN, UMOD, PLB1, CA6, and KLK3 were the top five proteins inversely associated with PAD risk. Incorporating 45 LASSO-selected proteins or a weighted protein risk score significantly enhanced PAD prediction beyond clinical variables alone, reaching a maximum C-index of 0.835. CONCLUSIONS This study identified plasma proteins associated with PAD risk in individuals with T2D. Adding proteomic data into the clinical model significantly improved PAD prediction.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917029","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":"Incidence and Risk Factors of Diagnosed Young-Adult-Onset Type 2 Diabetes in the U.S.: The National Health Interview Survey 2016–2022","authors":"Lan Xu, Jinjun Ran, Hui Shao, Meng Chen, Hao Tang, Yongxuan Li, Yaqing Xu, Yue Huang, Feng Tao, Zhenxiu Liu, Victor W. Zhong","doi":"10.2337/dc24-1699","DOIUrl":"https://doi.org/10.2337/dc24-1699","url":null,"abstract":"OBJECTIVE To estimate the incidence and identify risk factors for diagnosed type 2 diabetes (T2D) among young U.S. adults. RESEARCH DESIGN AND METHODS We analyzed 142,884 adults aged 18–79 years with self-reported diabetes type from the cross-sectional National Health Interview Survey in 2016–2022, representing the noninstitutionalized U.S. civilian population. Incidence of diagnosed T2D was calculated for three age groups: young-adult onset (18–44 years), middle-age onset (45–64 years), and older-adult onset (65–79 years); the latter two groups were included to highlight the distinct risk factor profile of young-adult-onset T2D. Multivariable logistic regressions were used to identify risk factors for young-adult-onset T2D. RESULTS The estimated incidence of diagnosed young-adult-onset T2D was 3.0 per 1000 adults (95% CI 2.6–3.5). Minority groups, socioeconomically disadvantaged individuals, and people with cardiometabolic diseases or psychological conditions had a higher incidence of diagnosed young-adult-onset T2D compared with their counterparts. Lipid-lowering medication use (adjusted odds ratio [aOR] 13.15, 95% CI 8.85–19.55), antihypertensive medication use (aOR 11.89, 95% CI 7.97–17.73), and obesity (BMI ≥30 vs. <25 kg/m2, aOR 10.89, 95% CI 6.69–17.7) were the strongest risk factors for young-adult-onset T2D; these risk factors, along with hypertension, hyperlipidemia, and coronary heart disease, were more strongly associated with young-adult-onset T2D compared with later-onset T2D, with up to 4.5 times higher aORs. CONCLUSIONS This study quantified the incidence of diagnosed young-adult-onset T2D in U.S. adults and identified its distinct risk factor profile. Targeted prevention strategies for young-adult-onset T2D are needed for minority and socioeconomically disadvantaged people and those with cardiometabolic diseases.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925017","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":"Time Below Range and Its Influence on Hypoglycemia Awareness and Severe Hypoglycemia: Insights From the Association of British Clinical Diabetologists Study","authors":"Harshal Deshmukh, Emma G. Wilmot, Pratik Choudhary, Emmanuel Ssemmondo, Dennis Barnes, Neil Walker, Chris Walton, Robert E.J. Ryder, Thozhukat Sathyapalan","doi":"10.2337/dc24-1833","DOIUrl":"https://doi.org/10.2337/dc24-1833","url":null,"abstract":"OBJECTIVE This study aimed to explore the relationship between time below range (TBR), impaired awareness of hypoglycemia (IAH), and severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS This cross-sectional study analyzed data from individuals with diabetes using continuous glucose monitors (CGMs) in the Association of British Clinical Diabetologists audit. Hypoglycemia awareness was assessed via the Gold score (≥4 denoting IAH), and SH was defined as hypoglycemia requiring third-party assistance. Logistic regression was used to determine the association between TBR percentage (<70 mg/dL; 3.9 mmol/L) at first follow-up and follow-up Gold score and SH incidence. The Youden J index identified optimal TBR percentage cutoffs for detecting IAH and SH. RESULTS The study included 15,777 participants, with follow-up TBR and SH data available for 5,029. The median TBR percentage was 4% (interquartile range 2–6.6%), with 42% meeting the recommended TBR of ≤4%. Adjusted for age, sex, and BMI, TBR was significantly associated with SH (P < 0.001) and IAH (P = 0.005). Optimal TBR cutoffs for identifying IAH and SH were 3.35% and 3.95%, yielding negative predictive value (NPV) values of 85% and 97%, respectively. CONCLUSIONS Our findings support the international consensus recommending a TBR of <4% in type 1 diabetes, with high NPV values suggesting the utility of TBR in screening for SH.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"18 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917177","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 Association Between Cost-Related Insulin Rationing and Health Care Utilization in U.S. Adults With Diabetes","authors":"Caroline G. Borden, Baylee F. Bakkila, Laura M. Nally, Kasia J. Lipska","doi":"10.2337/dc24-2117","DOIUrl":"https://doi.org/10.2337/dc24-2117","url":null,"abstract":"OBJECTIVE To examine the association between insulin rationing and health care utilization. RESEARCH DESIGN AND METHODS Cross-sectional study of all 2021 National Health Interview Survey respondents with diabetes using insulin. Logistic regression and zero-inflated negative binomial regression models examined associations between insulin rationing (skipping, delaying, or reducing insulin to save money) and 1) emergency department (ED) visit or hospitalization and 2) number of urgent care visits. All analyses were age-stratified and used survey weights. RESULTS Among 982 respondents representing 7,593,944 U.S. adults (median age 61, 47% women), 17% reported rationing. Among adults 18–64, rationing was not significantly associated with health care utilization. Among adults ≥65, rationing was associated with more urgent care visits (relative risk 2.1, 95% CI 1.2–3.6) but not with odds of ED visit or hospitalization (odds ratio 0.7, 95% CI 0.3–1.4). CONCLUSIONS Insulin rationing was not associated with higher health care utilization, but concurrent rationing of health care may mask a relationship.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"17 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917031","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":"Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1–5 Clinical Trials","authors":"Ellen M. Apperloo, Katherine R. Tuttle, Imre Pavo, Axel Haupt, Rebecca Taylor, Russell J. Wiese, Andrea Hemmingway, David Z. I. Cherney, Naveed Sattar, Hiddo J. L. Heerspink","doi":"10.2337/dc24-1773","DOIUrl":"https://doi.org/10.2337/dc24-1773","url":null,"abstract":"OBJECTIVE Tirzepatide, a long-acting, glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, reduced urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline in people with type 2 diabetes and high cardiovascular risk in the SURPASS-4 trial. To examine the generalizability of these findings, we assessed change from baseline in UACR for tirzepatide (5, 10, and 15 mg) compared with active and placebo treatment in a broad population from the SURPASS-1–5 trials. RESEARCH DESIGN AND METHODS This post hoc analysis examined data from the overall pooled SURPASS-1–5 population and subgroups defined by baseline UACR ≥30 mg/g. A mixed model for repeated measures was used to analyze on-treatment data from baseline to the end-of-treatment visit. Study identifier was included in the model as a covariate. RESULTS The adjusted mean percent change from baseline in UACR for tirzepatide 5, 10, or 15 mg compared with all pooled comparators was −19.3% (95% CI −25.5, −12.5), −22.0% (−28.1, −15.3), and −26.3 (−32.0, −20.0), respectively, at week 40/42. Results were similar across pooled placebo, active, and insulin comparator studies. UACR lowering appeared more pronounced in subgroups with UACR ≥30 mg/g. Mediation analysis findings suggested that approximately one-half of the reduction in albuminuria associated with tirzepatide may be weight loss related. There was no difference in eGFR between tirzepatide and pooled comparators at week 40/42. CONCLUSIONS In this post hoc analysis in people with type 2 diabetes, including those with chronic kidney disease, tirzepatide was associated with a clinically relevant decreased UACR versus comparators, suggesting a potential kidney-protective effect.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917032","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":"Proteomic and Metabolomic Signatures in Prediabetes Progressing to Diabetes or Reversing to Normoglycemia Within 1 Year","authors":"Marko Barovic, Joke Johanna Hahn, Annett Heinrich, Trishla Adhikari, Peter Schwarz, Peter Mirtschink, Alexander Funk, Stefan Kabisch, Andreas F.H. Pfeiffer, Matthias Blüher, Jochen Seissler, Norbert Stefan, Robert Wagner, Andreas Fritsche, Reiner Jumpertz von Schwartzenberg, Sarantis Chlamydas, Hani Harb, Christos S. Mantzoros, Triantafyllos Chavakis, Annette Schürmann, Andreas L. Birkenfeld, Michael Roden, Michele Solimena, Stefan R. Bornstein, Nikolaos Perakakis","doi":"10.2337/dc24-1412","DOIUrl":"https://doi.org/10.2337/dc24-1412","url":null,"abstract":"OBJECTIVE Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of people with prediabetes progressing to diabetes or reversing to normoglycemia within 1 year. RESEARCH DESIGN AND METHODS The fasting plasma concentrations of 1,389 proteins and the fasting, 30-min, and 120-min post–oral glucose tolerance test (OGTT) plasma concentrations of 152 metabolites were measured in up to 134 individuals with new-onset diabetes, prediabetes, or normal glucose tolerance. For 108 participants, the analysis was repeated with samples from 1 year before, when all had prediabetes. RESULTS The plasma concentrations of 14 proteins were higher in diabetes compared with normoglycemia in a population with prediabetes 1 year before, and they correlated with indices of insulin sensitivity. Higher levels of dicarbonyl/L-xylulose reductase and glutathione S-transferase A3 in the prediabetic state were associated with an increased risk of diabetes 1 year later. Pathway analysis pointed toward differences in immune response between diabetes and normoglycemia that were already recognizable in the prediabetic state 1 year prior at baseline. The area under the curve during OGTT of the concentrations of IDL particles, IDL apolipoprotein B, and IDL cholesterol was higher in new-onset diabetes compared with normoglycemia. The concentration of glutamate increased in prediabetes progressing to diabetes. CONCLUSIONS We identify new candidates associated with the progression of prediabetes to diabetes or its remission to normoglycemia. Pathways regulating the immune response are related to prediabetes trajectories.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"24 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917030","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}