Abstract
Background: South Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians. Methods: We examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40–84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication. Results: Average age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity. Conclusions: Metabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 668-673 |
| Number of pages | 6 |
| Journal | International Journal of Obesity |
| Volume | 48 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2024 |
Funding
MDG is supported by K23DK119404 from the National Institute of Diabetes and Digestive and Kidney Diseases. The MASALA study was supported by Grant Number R01HL093009 from the National Heart, Lung, And Blood Institute and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1RR024131. The metabolomic measurements were supported by an anonymous gift to Dr. Kanaya. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health. MGG is supported by funding from NIH-NIDDK and the MASALA study is supported by funding from NIH-NHLBI. The authors declare no financial conflicts of interest.
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
