Adaptation of β-Cell and Endothelial Function to Carbohydrate Loading: Influence of Insulin Resistance.

Abstract

High-carbohydrate diets have been associated with β-cell strain, dyslipidemia, and endothelial dysfunction. We examined how β-cell and endothelial function adapt to carbohydrate overloading and the influence of insulin resistance. On sequential days in randomized order, nondiabetic subjects (classified as insulin-sensitive [IS] [n = 64] or insulin-resistant [IR] [n = 79] by euglycemic clamp) received four mixed meals over 14 h with either standard (300 kcal) or double carbohydrate content. β-Cell function was reconstructed by mathematical modeling; brachial artery flow-mediated dilation (FMD) was measured before and after each meal. Compared with IS, IR subjects showed higher glycemia and insulin hypersecretion due to greater β-cell glucose and rate sensitivity; potentiation of insulin secretion, however, was impaired. Circulating free fatty acids (FFAs) were less suppressed in IR than IS subjects. Baseline FMD was reduced in IR, and postprandial FMD attenuation occurred after each meal, particularly with high carbohydrate, similarly in IR and IS. Throughout the two study days, higher FFA levels were significantly associated with lower (incretin-induced) potentiation and impaired FMD. In nondiabetic individuals, enhanced glucose sensitivity and potentiation upregulate the insulin secretory response to carbohydrate overloading. With insulin resistance, this adaptation is impaired. Defective suppression of endogenous FFA is one common link between impaired potentiation and vascular endothelial dysfunction.

• Authors: Barry E Hurwitz, Neil Schneiderman, Jennifer B Marks, Armando J Mendez, Alex Gonzalez, Maria M Llabre, Steven R Smith, Roberto Bizzotto, Eleonora Santini, Maria Laura Manca, Jay S Skyler, Andrea Mari, Ele Ferrannini
• Journal: Diabetes (Diabetes) Vol. 64 Issue 7 Pg. 2550-9 (Jul 2015) ISSN: 1939-327X [Electronic] United States
• PMID: 25754957 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Dietary Carbohydrates
• Fatty Acids, Nonesterified

Topics

• Adaptation, Physiological
• Adult
• Dietary Carbohydrates (administration & dosage)
• Endothelium, Vascular (physiology)
• Fatty Acids, Nonesterified (blood)
• Female
• Humans
• Insulin Resistance
• Insulin-Secreting Cells (physiology)
• Male
• Models, Theoretical
• Vasodilation