Rain Yamamoto1, Majken K Jensen1,2, Sarah Aroner1, Jeremy D Furtado1, Bernard Rosner3,4, Frank B Hu1,4, Beverley Balkau5, Andrea Natali6, Ele Ferrannini7, Simona Baldi6, Frank M Sacks1,4. 1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 2. Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 3. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. 4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 5. INSERM 1018, CESP, Clinical Epidemiology, University Paris-Saclay, UVSQ-UPS, 94800, Villejuif, France. 6. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 7. CNR Institute of Clinical Physiology, Pisa, Italy.
Abstract
CONTEXT: High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. OBJECTIVE: We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN MEASURES: 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. RESULTS: 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. CONCLUSION: 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.
CONTEXT: High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. OBJECTIVE: We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN MEASURES: 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. RESULTS: 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. CONCLUSION: 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.
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