Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study

Abstract

Aims/hypothesis: The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n = 85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA.

Methods: Youths with a diagnosis of type 1 (n = 60) or type 2 diabetes (n = 25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg⁻¹ min⁻¹). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA₁(c), lipids, blood pressure, urine albumin:creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n = 53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n = 33) and healthy control youths (n = 22).

Results: The best model included waist, triacylglycerol (TG) and HbA₁(c) levels (R² = 0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r = 0.65, p < 0.0001; r = 0.62, p = 0.002) with GDR on the two validation sets. Based on this analysis, we propose the following formula to estimate insulin sensitivity in youths with diabetes: [Formula: see text].

Conclusions/interpretation: Insulin sensitivity can be estimated in adolescents with diabetes using routinely collected measures. This score can be applied to epidemiological studies of youths with diabetes to characterise relationships between dimensions of diabetes type.

Fig. 1

Relationship between measured GDR and estimated IS score in (a) youths with diabetes (n=32), r=0.65, p<0.0001 (grey diamonds, type 1 diabetes; black squares, type 2 diabetes); (b) youths without diabetes (n=22), r=0.62, p=0.002 (black circles)

Fig. 2

Relationship between fasting C-peptide (FCP, nmol/l) and estimated IS score among all SEARCH participants (n=2,417): two-piece orthogonal regression splines. y1=−0.541x+4.309, y2=−0.00132x+0.151 with a knot at x=7.7 (IS score), y=0.14 (FCP in nmol/l)

Fig. 3

Relationship between fasting C-peptide and insulin sensitivity by DA status among SEARCH participants: smooth spline averages. DA-positive: black (n = 1,780). DA-negative: grey (n=610)