Defining insulin resistance from hyperinsulinemic-euglycemic clamps

Abstract

Objective: This study was designed to determine a cutoff point for identifying insulin resistance from hyperinsulinemic-euglycemic clamp studies performed at 120 mU/m(2)·min in a white population and to generate equations from routinely measured clinic and blood variables for predicting clamp-derived glucose disposal rate (GDR), i.e., insulin sensitivity.

Research design and methods: We assembled data from hyperinsulinemic-euglycemic clamps (120 mU/m(2)·min insulin dose) performed at the Pennington Biomedical Research Center between 2001 and 2011. Subjects were divided into subjects with diabetes (n = 51) and subjects without diabetes (n = 116) by self-report and/or fasting glucose ≥126 mg/dL.

Results: We found that 75% of individuals with a GDR <5.6 mg/kg fat-free mass (FFM) + 17.7·min were truly insulin resistant. Cutoff values for GDRs normalized for body weight, body surface area, or FFM were 4.9 mg/kg·min, 212.2 mg/m(2)·min, and 7.3 mg/kgFFM·min, respectively. Next, we used classification tree models to predict GDR from routinely measured clinical and biochemical variables. We found that individual insulin resistance could be estimated with good sensitivity (89%) and specificity (67%) from the homeostasis model assessment of insulin resistance (HOMA-IR) >5.9 or 2.8< HOMA-IR <5.9 with HDL <51 mg/dL.

Conclusions: We developed a cutoff for defining insulin resistance from hyperinsulinemic-euglycemic clamps. Moreover, we now provide classification trees for predicting insulin resistance from routinely measured clinical and biochemical markers. These findings extend the clamp from a research tool to providing a clinically meaningful message for participants in research studies, potentially providing greater opportunity for earlier recognition of insulin resistance.

Figures

Figure 1

Tree model for insulin resistance determined using all available body composition and blood measures. HOMA-IR and HDL were the only significant determinants in this model. The model is built on a randomly selected training cohort of 125 subjects and tested in 42 subjects. An arbitrary risk score of 0.25 is calculated. Therefore, if a terminal node has a >25% proportion, those subjects are more likely to be insulin resistant (dashed lines). The decision nodes for being insulin resistant are as follows: 1) HOMA-IR >5.9 and 2) 2.8< HOMA-IR <5.9 and HDL <51 mg/dL.

Figure 2

Tree model for insulin resistance using only fasting glucose, insulin, age, sex, and BMI. Only fasting insulin was a significant determinant in the model. The model is built on a randomly selected training cohort of 125 subjects and tested on 42 subjects. An arbitrary risk score of 0.25 is calculated. Therefore, if a terminal node has a >25% proportion, those subjects are more likely to be insulin resistant (dashed lines). The decision node for being insulin resistant is having a fasting insulin >10.6 μU/mL.