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- Title
HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study.
- Authors
Yamamoto, Rain; Jensen, Majken K.; Aroner, Sarah; Furtado, Jeremy D.; Rosner, Bernard; Hu, Frank B.; Balkau, Beverley; Natali, Andrea; Ferrannini, Ele; Baldi, Simona; Sacks, Frank M.
- Abstract
<bold>Context: </bold>High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects.<bold>Objective: </bold>We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3.<bold>Design, Setting, and Participants: </bold>A prospective cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and cardiovascular disease (RISC) study, a multicenter European clinical investigation, whose recruitment initiated in 2002, with a follow-up of 3 years.<bold>Main Measures: </bold>Insulin sensitivity was estimated from an oral glucose tolerance test at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich enzyme-linked immunosorbent assay (ELISA)-based method.<bold>Results: </bold>The 2 HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (P-trend = 0.01), compared to the lowest quintile. No significant association was observed for total HDL, and very low density lipoprotein (VLDL) and low density lipoprotein (LDL) containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III.<bold>Conclusion: </bold>Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.
- Subjects
INSULIN sensitivity; COHORT analysis; RESEARCH; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; APOLIPOPROTEINS; RESEARCH funding; HIGH density lipoproteins; GLUCOSE tolerance tests; INSULIN resistance; LONGITUDINAL method
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 8, pe2928
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab234