Multiyear Reproducibility of Clamp-Derived Insulin Sensitivity in Free-Living Humans—Association with Incident Prediabetes in the POP-ABC Study

Abstract

Background: The hyperinsulinemic euglycemic clamp (HEC) is the gold standard measure for insulin sensitivity (Si-clamp). Here, we determined its reproducibility and metabolic implications. Methods: POP-ABC is a follow-up study of healthy black and white offspring of parents with T2DM for the primary outcome of prediabetes. Assessments included clinical exam, OGTT, anthropometry, and HEC. Results: 90 adults (44 AA, 46 EA; 62 women, 28 men) who underwent HEC-1 at baseline consented to HEC-2 after 2.3y (range 2-3.5 y) (Table 1). The mean (SD) baseline age was 47.5 ± 8.13y, BMI was 30.4 ± 9.16 kg/m2, FPG was 94.8 ± 7.92 mg/dl and 2-hrPG was 127.4 ± 26.8. HEC-1 and HEC-2 metrics did not differ significantly (Table 1). Si-clamp values from HEC-1 and HEC-2 were strongly correlated (r=0.81, P<0.0001); the change in Si-clamp correlated with change in weight (r= 0.35, P=0.0009), but not age, gender, race, or FPG. After ∼5 y follow-up, 40 subjects progressed (P) to prediabetes and 50 were Nonprogressors (NP). Si-clamp was lower at baseline and 2.3 y later in P vs. NP (P=0.02). The mean change in Si-clamp (-2.5% in NP and -9.5% in P) predicted prediabetes risk (P=0.02). Conclusion: Insulin sensitivity by HEC is reproducible over multiyear intervals in nondiabetic free-living subjects. Progressors to prediabetes showed ∼4% /y decline in Si-clamp vs. 1%/y in nonprogressors. Disclosure N.A. Umekwe: None. D.J. James: None. S. Dagogo-Jack: None.