title: Relative conributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia.
abstract: We performed hyperglycemic clamps in 283 nondiabetic Caucasians and, with multiple linear regression, determined the contribution of beta-cell function and tissue insulin sensitivity to variations in glycemia and insulinemia during oral glucose tolerance tests (OGTTs). Impaired glucose tolerance (IGT) subjects had reduced insulin sensitivity (P < .02) and beta-cell function (P < .0001). Normal glucose tolerance (NGT) subjects with first-degree type 2 diabetic relatives had reduced first and second phase insulin secretion (both, P < .05), but normal insulin sensitivity (P = .37). Beta-Cell function and insulin sensitivity accounted for one fourth of the variability in glucose tolerance. Fasting plasma glucose in subjects with NGT (n = 185) was a function of both phases of insulin secretion and of insulin sensitivity (all, P < .05), whereas, in IGT subjects (n = 98), it was a function of first phase insulin secretion and insulin sensitivity (P < .01). Two-hour glycemia was a function of second phase secretion and insulin sensitivity (P < .01). Fasting and 2-hour plasma insulin levels were determined by insulin sensitivity (and glycemia) in NGT subjects (P < .001), but by second phase secretion in IGT (P < .001). We conclude that beta-cell function is reduced in subjects with IGT; glycemia and insulinemia are not regulated by the same mechanisms in IGT and NGT; insulin sensitivity does not contribute to insulinemia in IGT; family history of diabetes influences beta-cell function, but not insulin sensitivity in Caucasians.
authors.affiliation: Department of Internal Medicine, University Medical Center Utrecht, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: van Haeften
authors.forename: W
authors.initials: W
authors.lastname: Pimenta
authors.forename: A
authors.initials: A
authors.lastname: Mitrakou
authors.forename: M
authors.initials: M
authors.lastname: Korytkowski
authors.forename: T
authors.initials: T
authors.lastname: Jenssen
authors.forename: H
authors.initials: H
authors.lastname: Yki-Jarvinen
authors.forename: J E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin