Cross-sectional and longitudinal changes of glucose effectiveness in relation to glucose tolerance: the insulin resistance atherosclerosis study

Abstract

Objective: Glucose effectiveness (S(G)), the capacity of glucose to enhance its own disposition, is an independent predictor of future diabetes. However, there are data on cross-sectional and longitudinal changes of S(G) and its components, basal insulin effect on S(G) (BIE) and S(G) at zero insulin (GEZI), but the natural course of S(G) has not been described in a large population.

Research design and methods: S(G) was measured at baseline in 1,265 participants (aged 40-69 years) and at the 5-year examination in 827 participants in the Insulin Resistance Atherosclerosis Study (IRAS) using the frequently sampled intravenous glucose tolerance test. None of these participants were treated with glucose-lowering agents.

Results: In cross-sectional analyses, S(G), BIE, and GEZI deteriorated with worsening of glucose tolerance (P < 0.001 for all three associations). In longitudinal analyses among subjects with normal glucose tolerance (NGT) at baseline, S(G), BIE, and GEZI declined in those who progressed to impaired glucose tolerance (IGT) or diabetes (P < 0.001 for all three measures). More modest longitudinal changes were demonstrated in individuals with IGT. The transition back to NGT (as opposed to no change) compared with the transition to diabetes was statistically significant for S(G) (P = 0.049) and BIE (P = 0.042) and was not a statistically significant trend for GEZI (P = 0.332). In individuals with diabetes, only BIE had a significant decline (P = 0.003).

Conclusions: S(G), BIE, and GEZI decline in subjects whose glycemic status worsens. S(G) and GEZI deteriorate more in the initial stages of the disease process.

Figure 1

Cross-sectional analysis of the relationship between S_I, AIR, S_G, BIE, and GEZI and fasting and 2-h glucose levels. ○, S_I; ●, AIR; □, S_G; ■, BIE; △, GEZI. All results were adjusted for age, sex, race/ethnicity, and research center.

Figure 2

Yearly changes in S_G, BIE, and GEZI relative to the change in glucose tolerance status. A: Yearly changes in S_G. Results were adjusted for age, sex, race/ethnicity, research center, and baseline S_G. B: Yearly changes in BIE. Results were adjusted for age, sex, race/ethnicity, research center, and baseline log BIE. C: Yearly changes in GEZI. Results were adjusted for age, sex, race/ethnicity, research center, and baseline GEZI. Results were stratified by glucose tolerance status at the baseline and follow-up examinations: ○, NGT at baseline and follow-up; ●, NGT at baseline and IGT at follow-up; □, NGT at baseline and diabetes at follow-up; ■, IGT at baseline and NGT at follow-up; △, IGT at baseline and follow-up; ▲, IGT at baseline and diabetes at follow-up; ◇, diabetes at baseline and follow-up.