title: The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance.
abstract: To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT (n = 293) and IGT (n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as DeltaISR/DeltaG / IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(-0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0-30 min) was correlated with the increase in FPG in both NGT and IGT (r = -0.43, P < 0.0001 and r = -0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60-120 min) and FPG was not significant. In conclusion, small increments in FPG, within the "normal" range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.
authors.affiliation: Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Abdulghani@uthscsa.edu
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Abdul-Ghani
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuda
authors.forename: Rucha
authors.initials: R
authors.lastname: Jani
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Jenkinson
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Coletta
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002097:C-Reactive Protein