Isolated Impaired Fasting Glucose and Peripheral Insulin Sensitivity:

Objective: In a recent consensus statement, the American Diabetes Association (ADA) concluded that individuals with impaired fasting glucose (IFG) have " normal muscle insulin sensitivity. " To subject this conclusion to further validation, we evaluated the relationship between glucose tolerance categories and peripheral insulin sensitivity in a large nondiabetic population. Research Design and Methods: Insulin sensitivity was directly quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 446 nondiabetic individuals, divided into four groups: normal glucose tolerance (NGT, n= 318), isolated IFG (n=63), isolated impaired glucose tolerance (IGT, n=33), and combined IFG and IGT (IFG/IGT) (n=32). Results: Insulin sensitivity was significantly different in all three groups with prediabetes (IFG, IGT, IFG/IGT) as compared with NGT (p<0.05). Using tertiles of SSPG concentration in the NGT group as operational definitions of insulin resistance (highest tertile) and insulin sensitivity (lowest tertile), there was considerable heterogeneity within the prediabetic groups. Thus, 57% of IFG individuals were insulin resistant, and 13% were insulin sensitive. The IFG/IGT group was most homogeneous with 94% classified as insulin resistant and only 3% as insulin sensitive. Conclusions: Peripheral insulin sensitivity varies considerably in nondiabetic individuals with IFG individuals showing the most heterogeneity within the prediabetes group. We believe that this heterogeneity in insulin sensitivity, and the relatively few patients in whom insulin sensitivity has been measured directly in the past, explain the discrepancy between our findings and the recent consensus statement by the ADA. IFG and Insulin Sensitivity easurements of plasma glucose concentration before and two hours (2-hr) after a 75 gram oral glucose challenge provide the information needed to divide individuals into three major diagnostic groups: normal glucose tolerance (NGT), prediabetes, and diabetes (1). These data can also be used to further subdivide individuals with prediabetes into those with isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or a combination of IFG and IGT (IFG/IGT) (1). The pathophysiological differences between the three categories with prediabetes has been the focus of several reports (2-12), with general agreement that peripheral insulin resistance is the prominent finding in individuals with either isolated IGT or combined IFG/IGT. The findings are less consistent in individuals with isolated IFG, who have been described as having both normal (2-4) and abnormal (5-12) peripheral insulin sensitivities. The reasons for the discrepant findings in persons with IFG are not clear, and may relate to the use of different methods …