Serum Metabolomics of Incident Diabetes and Glycemic Changes in a Population With High Diabetes Burden: The Hispanic Community Health Study/Study of Latinos

Abstract

Metabolomic signatures of incident diabetes remain largely unclear for US Hispanics/Latinos, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at baseline (2008-2011). On the basis of the significant metabolites associated with incident diabetes, metabolite modules were detected using topological network analysis and their associations with incident diabetes and longitudinal changes in cardiometabolic traits were further examined. There were 224 incident cases of diabetes after on average 6 years of follow-up. After adjustment for sociodemographic, behavioral and clinical sociodemographic and clinical diabetes risk factors, 134 metabolites were associated with incident diabetes (FDR-adjusted P<0.05). We identified 10 metabolite modules, including modules comprised of previously reported diabetes-related metabolites (e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, and glycine) and two reflecting potentially novel metabolite groups (e.g., threonate, N-methylproline, oxalate, and tartarate in a plant-food metabolite module; and androstenediol sulfates in an androgenic-steroid metabolite module). The plant-food metabolite module and its components were associated with higher diet quality (especially higher intakes of healthy plant-based foods), lower risk of diabetes, and favorable longitudinal changes in HOMA-IR. The androgenic-steroid module and its component metabolites decreased with increasing age and were associated with higher risk of diabetes and greater increases in 2-h glucose over time. We replicated the associations of both modules with incident diabetes in a US cohort of non-Hispanic Blacks and Whites (n = 1754). Among US Hispanics/Latinos we identified metabolites across various biological pathways, including those reflecting androgenic steroids and plant-derived foods, associated with incident diabetes and changes in glycemic traits, highlighting the importance of hormones and dietary intake in the pathogenesis of diabetes.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

“…We found that the biosynthesis of valine, leucine and isoleucine belonging to branched chain amino acids (BCAAs), and of phenylalanine, tyrosine and tryptophan belonging to aromatic amino acids (AAAs) was enriched in PDR group, compared with HC group. Increasing evidence reported that BCAAs and AAAs were predictors of occurrence and development of T2D [63][64][65] , which was consist with previous study. Of note, more data pointed that arginine biosynthesis, lysine degradation, histidine and D-ornithine catabolism were enriched in PDR group.…”

Blood metabolomic shift links diet and gut microbiota to multiple health outcomes among Hispanic/Latino immigrants in the U.S.

“…Finally, we discovered that U.S. nativity related metabolites were collectively associated with representative clinical traits reflecting blood glycemic and lipid profiles, liver function, kidney function, and lung function, to a greater extent than metabolites unrelated to U.S. nativity. Additionally, U.S. nativity related metabolites were collectively overlapped with these metabolites associated with representative common diseases that are prevalent among Hispanics/Latinos in the U.S. Hispanics/Latinos in the U.S. have a high burden of multiple chronic diseases [31,48,49], and prior studies have attempted to pinpoint one or multiple causal factors [13,50,51]. However, our study suggests that a systemic metabolomic shift in metabolic patterns, resulting from the adoption of U.S. lifestyle due to multiple risk factors, significantly contributes to this multifaceted disease burden.…”

Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes

“…Metabolic traits, including body mass index, waist-hip ratio, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, fasting glucose, after 2-hour glucose, HbA1c, and homeostatic model assessment for insulin resistance, were measured following standardized methods and protocols. 17,18…”

“…T2D cases were identified if participants met at least one of the following criteria 17 : fasting glucose ≥7.0 mmol/L (126 mg/dL); after 2-hour glucose ≥11.1 mmol/L (200 mg/dL); HbA1c ≥6.5%; or self-reported antidiabetic medication use. Participants free of diabetes at baseline who were identified as having T2D during the follow-up visits were deemed to be incident T2D.…”