Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

TitleSerum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Publication TypeJournal Article
Year of Publication2020
AuthorsChen G-C, Chai JChoul, Yu B, Michelotti GA, Grove ML, Fretts AM, Daviglus ML, Garcia-Bedoya OL, Thyagarajan B, Schneiderman N, Cai J, Kaplan RC, Boerwinkle E
Secondary AuthorsQi Q
JournalAm J Clin Nutr
Volume112
Issue1
Pagination57-65
Date Published2020 07 01
ISSN1938-3207
KeywordsAdolescent, Adult, Aged, Diabetes Mellitus, Female, Hispanic Americans, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Sphingolipids, United States, Young Adult
Abstract

BACKGROUND: Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.

OBJECTIVES: We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.

METHODS: We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 y who were free of diabetes and other major chronic diseases at baseline (2008-2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.

RESULTS: There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend 

CONCLUSIONS: Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344.

DOI10.1093/ajcn/nqaa114
Alternate JournalAm J Clin Nutr
PubMed ID32469399
PubMed Central IDPMC7326587
Grant ListUM1 HG008898 / HG / NHGRI NIH HHS / United States
K01 HL129892 / HL / NHLBI NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
R01 HL140976 / HL / NHLBI NIH HHS / United States
R01 HL136266 / HL / NHLBI NIH HHS / United States
R01 DK120870 / DK / NIDDK NIH HHS / United States
R01 DK119268 / DK / NIDDK NIH HHS / United States