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Differences in Insulin Resistance in Nondiabetic Subjects With Isolated Impaired Glucose Tolerance or Isolated Impaired Fasting Glucose

¹ Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
² Eli Lilly and Company, Area Medical Center, Vienna, Austria
³ Department of Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina
⁴ Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada
⁵ Kaiser Research Center, Northern California, Oakland, California
⁶ Department of Medicine, UCLA School of Medicine, Los Angeles, California

Both impaired glucose tolerance (IGT) (as defined by the 1985 World Health Organization criteria) and impaired fasting glucose (IFG) (as defined by the 1997 American Diabetes Association criteria) represent intermediate metabolic states between normal and diabetic glucose homeostasis. Cardiovascular disease may be related to postglucose load rather than fasting glycemia, i.e., IGT rather than IFG. We hypothesized that subjects with IGT may be more insulin resistant and have higher levels of common cardiovascular risk factors than those with isolated IFG. In the Insulin Resistance Atherosclerosis Study (IRAS), we studied S_i and first-phase insulin secretion (acute insulin response [AIR]), as derived from a frequently sampled intravenous glucose tolerance test, as well as common cardiovascular risk factors in four different glucose tolerance categories (NFG/NGT [n = 654], NFG/IGT [n = 255], IFG/NGT [n = 59], and IFG/IGT [n = 102]) among nondiabetic subjects. Subjects with isolated postchallenge hyperglycemia (NFG/IGT) had lower S_i (means ± SE: 2.10 ± 0.04 vs. 2.59 ± 0.13 x 10^–4 min^–1 · µU^–1 · ml^–1; P = 0.005), lower proinsulin levels (34.4 ± 1.8 vs. 42.0 ± 4.5 pmol/l; P = 0.03), higher AIR (273.1 ± 18.1 vs. 215.9 ± 30.0 pmol/l; P = 0.04), higher C-reactive protein (2.49 ± 0.3 vs. 1.49 ± 0.5 mg/l; P = 0.0015), and higher triglyceride levels (137.7 ± 5.5 vs. 108.4 ± 8.9 mg/dl; P = 0.0025) than subjects with isolated fasting hyperglycemia (IFG/NGT). The relation of insulin resistance to glucose tolerance category was consistently seen in women and men and across the three ethnic groups of the IRAS (non-Hispanic whites, African Americans, and Hispanics). Nondiabetic individuals with isolated postchallenge hyperglycemia (IGT) are more insulin resistant than individuals with isolated fasting hyperglycemia (IFG). The risk factor pattern (including increased insulin resistance) seen in isolated IGT identifies a subgroup of nondiabetic individuals who are likely to benefit from early intervention.

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