Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men

Abstract

Objective: We evaluated insulin sensitivity and insulin secretion across the entire range of fasting (FPG) and 2-h plasma glucose (PG), and we investigated the differences in insulin sensitivity and insulin release in different glucose tolerance categories.

Research design and methods: A total of 6,414 Finnish men (aged 57 +/- 7 years, BMI 27.0 +/- 3.9 kg/m2) from our ongoing population-based METSIM (Metabolic Syndrome in Men) study were included. Of these subjects, 2,168 had normal glucose tolerance, 2,859 isolated impaired fasting glucose (IFG), 217 isolated impaired glucose tolerance (IGT), 701 a combination of IFG and IGT, and 469 newly diagnosed type 2 diabetes.

Results: The Matsuda index of insulin sensitivity decreased substantially within the normal range of FPG (-17%) and 2-h PG (-37%) and was approximately -65 and -53% in the diabetic range of FPG and 2-h PG, respectively, compared with the reference range (FPG and 2-h PG <5.0 mmol/l). Early-phase insulin release declined by only approximately -5% within the normal range of FPG and 2-h PG but decreased significantly in the diabetic range of FPG (by 32-70%) and 2-h PG (by 33-51%). Changes in insulin sensitivity and insulin secretion in relation to hyperglycemia were independent of obesity. The predominant feature of isolated IGT was impaired peripheral insulin sensitivity. Isolated IFG was characterized by impaired early and total insulin release.

Conclusions: Peripheral insulin sensitivity was already decreased substantially at low PG levels within the normoglycemic range, whereas impairment in insulin secretion was observed mainly in the diabetic range of FPG and 2-h PG. Obesity did not affect changes in insulin sensitivity or insulin secretion in relation to hyperglycemia.

FIG. 1.

Insulin sensitivity (Matsuda ISI) (A and B), early-phase insulin release (InsAUC₃₀/GluAUC₃₀) (C and D), and total insulin release during the OGTT (InsAUC₁₂₀/GluAUC₁₂₀) (E and F) across the categories of FPG and 2-h PG. Bars display the value of insulin sensitivity or insulin release relative to the reference category (FPG <5.0 mmol/l, 2-h PG <5.0 mmol/l). Calculations were based on geometric means, adjusted for age and BMI with the general linear model. Cutoff values for different categories of FPG were (in mg/dl): 90.1 (5.0 mmol/l), 99.1 (5.5 mmol/l), 108.1 (6.0 mmol/l), 117.1 (6.5 mmol/l), 126.1 (7.0 mmol/l), 135.1 (7.5 mmol/l), 144.1 (8.0 mmol/l), 153.2 (8.5 mmol/l), and 162.2 (9.0 mmol/l). Cutoff values for different categories of 2-h PG were (in mg/dl): 90.1 (5.0 mmol/l), 108.1 (6.0 mmol/l), 126.1 (7.0 mmol/l), 144.1 (8.0 mmol/l), 162.2 (9.0 mmol/l), 180.2 (10.0 mmol/l), 198.2 (11.0 mmol/l), 216.2 (12.0 mmol/l), and 234.2 (13.0 mmol/l).

FIG. 2.

Disposition indexes corresponding to early-phase (DI₃₀ = Matsuda ISI × InsAUC₃₀/GluAUC₃₀) and total insulin release (DI₁₂₀ = Matsuda ISI × InsAUC₁₂₀/GluAUC₁₂₀) across the categories of FPG (A) and 2-h PG (B). Cutoff values for different categories of FPG and 2-h PG are as explained in Fig. 1.

FIG. 3.

Insulin sensitivity (Matsuda ISI) (A and B), early-phase insulin release (InsAUC₃₀/GluAUC₃₀) (C and D), and total insulin release in an OGTT (InsAUC₁₂₀/GluAUC₁₂₀) (E and F) across the categories of FPG and 2-h PG in nonobese (BMI <27 kg/m²; ▲) and obese subjects (BMI ≥27 kg/m²; ■). Bars display insulin sensitivity or insulin release relative to the reference category (FPG <5.0 mmol/l, 2-h PG <5.0 mmol/l). Calculations were based on geometric means, adjusted for age and BMI, with the general linear model (performed separately in subgroups of nonobese and obese subjects). Cutoff values for different categories of FPG and 2-h PG are as explained in Fig. 1. Ref., reference.

FIG. 4.

Insulin sensitivity (Matsuda ISI and 1/HOMA-IR) (A and B), early-phase insulin release (InsAUC₃₀/GluAUC₃₀) (C), total insulin release (InsAUC₁₂₀/GluAUC₁₂₀) (D), disposition index for early insulin release (DI₃₀ = Matsuda ISI × InsAUC₃₀/GluAUC₃₀) (E), and disposition index for total insulin release (DI₁₂₀ = Matsuda ISI × InsAUC₁₂₀/GluAUC₁₂₀) (F) in different categories of glucose tolerance. Bars show percentage of each index relative to NGT (reference, 100%). Calculations were based on geometric means, adjusted for age and BMI (ANCOVA). All pairwise comparisons were statistically significant (P < 0.05, Bonferroni post hoc test) except for those marked: *P > 0.05 vs. NGT, †P > 0.05 vs. isolated IFG, ‡P > 0.05 vs. isolated IGT. Ref., reference. IIFG, isolated IFG; IIGT, isolated IGT; NewDM, newly diagnosed diabetes.