Diabetes Care最新文献

{"title":"Diabetes Risk After Treatment for Childhood and Young Adult Cancer","authors":"Kirsten J. Cromie, Robert D. Murray, Ramzi A. Ajjan, Nicola F. Hughes, Richard G. Feltbower, Adam W. Glaser","doi":"10.2337/dc24-2171","DOIUrl":"https://doi.org/10.2337/dc24-2171","url":null,"abstract":"OBJECTIVE Diabetes is a potential late consequence of childhood and young adult cancer (CYAC) treatment. Causative treatments associated with diabetes have been identified in retrospective cohort studies but have not been validated in population-based cohorts. Our aim was to define the extent of diabetes risk and explore contributory factors for its development in survivors of CYAC in the United Kingdom. RESEARCH DESIGN AND METHODS Cancer registration data (n = 4,238) were linked to electronic health care databases to identify cases of diabetes through clinical coding or HbA1c values. Total effect of prespecified treatment exposures on diabetes risk was estimated using flexible parametric modeling and standardized cause-specific cumulative incidence functions (CIFs). RESULTS After median follow-up of 14.4 years, 163 individuals (3.8%) were identified with diabetes. Total body irradiation (TBI) increases diabetes risk over time, with a 40-year CIF reaching 21.0% (95% CI 13.8–31.9) compared with 8.4% (95% CI 6.1–11.5) without TBI. Survivors treated with corticosteroids had a 7.7% increased risk at 40 years after cancer diagnosis. Hematopoietic stem cell transplant (HSCT) survivors had markedly higher risk, with a 40-year CIF of 19.6% (95% CI 13.4–28.6) versus 8.2% (95% CI 6.0–11.3) for patients who had not undergone HSCT. Among patients who received allogeneic HSCT, the 40-year CIF of diabetes was 25.7% (95% CI 17.4–38.0), compared with 7.9% (95% CI 3.3–19.1) in patients who received autologous transplants. CONCLUSIONS This evaluation of a hospital-based cohort of patients with CYAC identifies these patients’ increased long-term risk of developing diabetes and how this varies temporally according to treatment modalities. Notable contrasts in risk by treatment were detected as early as 10 years after cancer diagnosis. Findings should inform the development of risk-stratified evidence-based screening.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"35 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031087","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":"Additive Value of Polygenic Risk Score to Family History for Type 2 Diabetes Prediction: Results From the All of Us Research Database","authors":"Emily Drzymalla, Laura Raffield, Katherine Kolor, Alain Koyama, Ramal Moonesinghe, Meda E. Pavkov, Cassandra N. Spracklen, Muin J. Khoury","doi":"10.2337/dc24-1537","DOIUrl":"https://doi.org/10.2337/dc24-1537","url":null,"abstract":"OBJECTIVE The goal of this study was to assess the additive value of considering type 2 diabetes (T2D) polygenic risk score (PRS) in addition to family history for T2D prediction. RESEARCH DESIGN AND METHODS Data were obtained from the All of Us (AoU) research database. First-degree T2D family history was self-reported on the personal family history health questionnaire. A PRS was constructed from 1,289 variants identified from a large multiancestry genome-wide association study meta-analysis for T2D. Logistic regression models were run to generate odds ratios (ORs) and 95% CIs for T2D. All models were adjusted for age, sex, and BMI. RESULTS A total of 109,958 AoU research participants were included in the analysis. The odds of T2D increased with 1 SD PRS (OR 1.75; 95% CI 1.71–1.79) and positive T2D family history (OR 2.32; 95% CI 2.20–2.43). In the joint model, both 1 SD PRS (OR 1.69; 95% CI 1.65–1.72) and family history (OR 2.06; 95% CI 1.98–2.15) were significantly associated with T2D, although the ORs were slightly attenuated. Predictive models that included both the PRS and family history (area under the curve [AUC] 0.794) performed better than models including only family history (AUC 0.763) or the PRS (AUC 0.785). CONCLUSIONS In predicting T2D, inclusion of a T2D PRS in addition to family history of T2D (first-degree relatives) added statistical value. Further study is needed to determine whether consideration of both family history and a PRS would be useful for clinical T2D prediction.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020557","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":"Lessons Learned From Epidemiology of Type 2 Diabetes in South Asians: Kelly West Award Lecture 2024","authors":"Viswanathan Mohan","doi":"10.2337/dci24-0046","DOIUrl":"https://doi.org/10.2337/dci24-0046","url":null,"abstract":"South Asia has high prevalence rates of type 2 diabetes (T2D). Until the 1990s, the prevalence of T2D within South Asia was low but much higher in the South Asian diaspora living abroad. Today, high prevalence rates of T2D are reported among those living in South Asia. T2D in South Asians presents with unique clinical features described as the “South Asian phenotype” that include younger age at onset of diabetes than in White Europeans, much lower BMI, hyperinsulinemia and greater insulin resistance, rapid decline in β-cell function resulting in low insulin reserve, low muscle mass, and greater ectopic fat deposition, especially in the liver. Also, prevalence of impaired fasting glucose is higher among South Asians than prevalence of impaired glucose tolerance. Genetic predisposition combined with intrauterine fetal programming (low vitamin B12 intake and high folate intake) increases susceptibility to T2D, from birth. In later life, overnutrition, especially a high carbohydrate intake with refined grains of higher glycemic index, coupled with low physical activity likely triggers the T2D epidemic in South Asians. Additionally, there are emerging risk factors like air pollution. Preventing T2D in South Asians requires a multifactorial approach, including improvements in maternal and fetal nutrition with special reference to vitamin B12 and folate intake, decreasing refined carbohydrate and increasing protein and fiber intake in the diet, increasing physical activity, and control of air pollution. Lessons learned from epidemiology of T2D in South Asians could be useful to other developing countries that are in earlier stages of epidemiological transition.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials","authors":"Hon Jen Wong, Bryan Sim, Yao Hao Teo, Yao Neng Teo, Mark Y. Chan, Leonard L.L. Yeo, Pei Chia Eng, Benjamin Y.Q. Tan, Naveed Sattar, Mayank Dalakoti, Ching-Hui Sia","doi":"10.2337/dc24-1678","DOIUrl":"https://doi.org/10.2337/dc24-1678","url":null,"abstract":"OBJECTIVE To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity. RESEARCH DESIGN AND METHODS We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation. RESULTS Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of −4.57 kg (95% CI −5.35 to −3.78), mean BMI reduction of −2.07 kg/m2 (95% CI −2.53 to −1.62), and mean waist circumference reduction of −4.55 cm (95% CI −5.72 to −3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations. CONCLUSIONS GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"12 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020559","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":"Derivation and Validation of D-RISK: An Electronic Health Record–Driven Risk Score to Detect Undiagnosed Dysglycemia in Clinical Practice","authors":"Michael E. Bowen, Ildiko Lingvay, Luigi Meneghini, Brett Moran, Noel O. Santini, Song Zhang, Ethan A. Halm","doi":"10.2337/dc24-1624","DOIUrl":"https://doi.org/10.2337/dc24-1624","url":null,"abstract":"OBJECTIVE We derive and validate D-RISK, an electronic health record (EHR)-driven risk score to optimize and facilitate screening for undiagnosed dysglycemia (prediabetes + diabetes) in clinical practice. RESEARCH DESIGN AND METHODS We used retrospective EHR data (derivation sample) and a prospective diabetes screening study (validation sample) to develop D-RISK. Logistic regression with backward selection was used to predict dysglycemia (HbA1c ≥5.7%) using diabetes risk factors consistently captured in structured EHR data. Model coefficients were converted to a points-based risk score. We report discrimination, sensitivity, and specificity and compare D-RISK to the American Diabetes Association (ADA) risk test and the ADA and United States Preventive Services Task Force (USPSTF) screening guidelines. RESULTS The derivation cohort included 11,387 patients (mean age 48 years; 65% female; 42% Hispanic; 32% non-Hispanic Black; mean BMI 32; 29% with hypertension). D-RISK included age, race, BMI, hypertension, and random glucose. The area under curve (AUC) for the risk score was 0.75 (95% CI 0.74–0.76). In the validation screening study (n = 519), the AUC was 0.71 (95% CI 0.66–0.75) which was better than the ADA and USPSTF diabetes screening guidelines (AUC = 0.52 and AUC = 0.58, respectively; P < 0.001 for both). Discrimination was similar to the ADA risk test (AUC = 0.67) using patient-reported data to supplement EHR data, although D-RISK was more sensitive (75% vs. 61%) at the recommended screening thresholds. CONCLUSIONS Designed for use in EHR, D-RISK performs better than commonly used screening guidelines and risk scores and may help detect undiagnosed cases of dysglycemia in clinical practice.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988461","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":"Financial Incentives, Income Supplementation, Cash Transfer, and Universal Basic Income Interventions in Diabetes: Understanding Differences and Effectiveness: A Scoping Review","authors":"Leonard E. Egede, Jennifer A. Campbell, Sebastian Linde, Rebekah J. Walker","doi":"10.2337/dci24-0072","DOIUrl":"https://doi.org/10.2337/dci24-0072","url":null,"abstract":"The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"52 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981448","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":"Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial","authors":"Ida M. Mynarek, Lars Krogvold, Freja B. Mørk, Trine W. H. Lawaetz, Trine Roald, Morten W. Fagerland, Nina Lindblom, Jacob Westman, Peter Barker, Heikki Hyöty, Johnny Ludvigsson, Kristian F. Hanssen, Jesper Johannesen, Knut Dahl-Jørgensen","doi":"10.2337/dc24-2121","DOIUrl":"https://doi.org/10.2337/dc24-2121","url":null,"abstract":"OBJECTIVE In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis. RESEARCH DESIGN AND METHODS This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6–15.9 years newly diagnosed with T1D. Antiviral treatment (pleconaril and ribavirin) or placebo was given for 6 months from diagnosis, and participants were followed for 3 years. The primary outcome was residual C-peptide secretion, reported as the area under the curve (AUC), assessed by 2-h mixed-meal tolerance test. Secondary outcomes included insulin doses and HbA1c. RESULTS At the 3-year follow-up, 75 participants attended. At 2 years, the mean ± SD AUC for C-peptide in the placebo group was 0.27 ± 0.33 compared with 0.34 ± 0.37 in the pleconaril and ribavirin group. After 3 years, the AUC had decreased to 0.17 ± 0.23 and 0.25 ± 0.34, respectively. There was no statistically significant difference between the groups. The groups were also comparable with regard to secondary end points. CONCLUSIONS The decreased reduction in C-peptide levels after antiviral treatment is no longer present after 2 or 3 years. Further investigations are needed to explore options to use antiviral treatment in the prevention and treatment of T1D.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"43 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974557","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":"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}