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Diabetes. 2018 Aug;67(8):1663-1672. doi: 10.2337/db17-1449. Epub 2018 Mar 27.

Circulating Sphingolipids, Insulin, HOMA-IR, and HOMA-B: The Strong Heart Family Study.

Author information

1
Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA rozenl@uw.edu.
2
Department of Biostatistics, University of Washington, Seattle, WA.
3
Department of Laboratory Medicine, University of Washington, Seattle, WA.
4
Boston Heart Diagnostics, Framingham, MA.
5
Cardiovascular Health Research Unit, Department of Medicine, School of Medicine, University of Washington, Seattle, WA.
6
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA.
7
MedStar Health Research Institute, Hyattsville, MD, and Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC.
8
New York Academy of Medicine, New York, NY.
9
Department of Internal Medicine, University of New Mexico, Albuquerque, NM.

Abstract

Experimental studies suggest ceramides may play a role in insulin resistance. However, the relationships of circulating ceramides and related sphingolipids with plasma insulin have been underexplored in humans. We measured 15 ceramide and sphingomyelin species in fasting baseline samples from the Strong Heart Family Study (SHFS), a prospective cohort of American Indians. We examined sphingolipid associations with both baseline and follow-up measures of plasma insulin, HOMA of insulin resistance (HOMA-IR), and HOMA of β-cell function (HOMA-B) after adjustment for risk factors. Among the 2,086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0 (16 carbons, 0 double bond), 18:0, 20:0, or 22:0 were associated with higher plasma insulin and higher HOMA-IR at baseline and at follow-up an average of 5.4 years later. For example, a twofold higher baseline concentration of ceramide 16:0 was associated with 14% higher baseline insulin (P < 0.0001). Associations between sphingomyelin species carrying 18:0, 20:0, 22:0, or 24:0 and insulin were modified by BMI (P < 0.003): higher levels were associated with lower fasting insulin, HOMA-IR, and HOMA-B among those with normal BMI. Our study suggests lowering circulating ceramides might be a target in prediabetes and targeting circulating sphingomyelins should take into account BMI.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00005134.

Comment in

PMID:
29588286
PMCID:
PMC6054436
[Available on 2019-08-01]
DOI:
10.2337/db17-1449
[Indexed for MEDLINE]
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