THE SHORT INSULIN TOLERANCE-TEST FOR DETERMINATION OF INSULIN SENSITIVITY - A COMPARISON WITH THE EUGLYCEMIC CLAMP

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate K(ITT) in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose K(ITT) over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mu-mol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed. A close correlation was found between the glucose disappearance rate K(ITT) and M/I values derived from the ITT and euglycaemic clamp, respectively, in both the normal (r = 0.86, p < 0.01) and the diabetic subjects (r = 0.81; p < 0.01) when arterialized blood was used but correlations were not significant with the venous blood sampling. The ITT was reproducible with a CV of 6%. The results suggest that the ITT is a suitable method of assessing insulin sensitivity and will be particularly useful in epidemiological studies, although the requirement for arterialized blood adds a measure of complexity.