Distinct β-cell defects in impaired fasting glucose and impaired glucose tolerance

Abstract

To characterize the defects in β-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, β-cell glucose sensitivity and rate sensitivity during the oral glucose tolerance test were measured with the model by Mari in 172 Mexican Americans. A subgroup (n=70) received a 2-h hyperglycemic clamp (+125 mg/dL), and first- and second-phase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in β-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased β-cell rate sensitivity. In IFG subjects, the defect in β-cell glucose sensitivity was time dependent, began to improve after 60 min, and was comparable to NGT after 90 min. The incremental area under the plasma C-peptide concentration curve during the first 12 min of the hyperglycemic clamp (ΔC-pep[AUC]0-12) was inversely related with the increase in FPG concentration (r=-36, r=0.001), whereas ΔC-pep[AUC]15-120 positively correlated with FPG concentration (r=0.29, r<0.05). When adjusted for the prevailing level of insulin resistance, first-phase insulin secretion was markedly decreased in both IFG and IGT, whereas second-phase insulin secretion was decreased only in IGT. These results demonstrate distinct defects in β-cell function in IFG and IGT.

FIG. 1.

Plasma glucose concentration (A) and insulin secretory rate (B) in subjects with IFG (n = 46), IGT (n = 48), and NGT (n = 78).

FIG. 2.

A: β-Cell glucose sensitivity in IFG, IGT, and NGT subjects derived with the model by Mari. B: The ratio between the increment in insulin secretory rate above baseline and increment in plasma glucose concentration above the fasting level at each time point through the OGTT. *P < 0.05; **P < 0.01.

FIG. 3.

Relationship between incremental area under the plasma C-peptide curve during the first phase (0–12 min, left) and second phase (15–120 min, right) of the hyperglycemic clamp. Triangles represent NGT subjects, open circles represent IGT subjects, and closed circles represent IFG subjects.