The roles of hyperandrogenemia and obesity in the syndrome of severe insulin resistance with acanthosis nigricans were evaluated in studies of 11 females with this condition. Our results in these subjects were compared to evaluations of control subjects matched for degree of androgen excess or obesity. Fasting insulin levels were 3-, 5-, and 15-fold higher in the obese (OB), hyperandrogenemic (HO), and acanthosis nigricans (AN) groups, respectively, when compared to normal females. Responsiveness to a standard bolus of exogenous insulin was 78% of normal in the OB group, 40% of normal in the HO group, and 30% of normal in the AN group. Insulin binding to monocytes from both the OB group, and the HO group was modestly diminished primarily due to decreased receptor number. As a group, AN subjects when compared to either normal or weight-matched controls, demonstrated a significant decease in monocyte insulin binding predominantly due to a decrease in receptor number. However, two patients in the AN group had normal insulin binding suggesting a postreceptor mechanism for the insulin resistance in at least some of these subjects. In vivo glucose utilization insulin dose response curves were determined in 3 acanthotic subjects using the euglycemic clamp technique. All 3 of these subjects had a right shift of the curve and diminished maximal utilization, consistent with combined receptor and postreceptor defects in insulin action. In evaluating the relationship between hypeandrogenemia, insulin resistance, and acanthosis nigricans, significant correlations among basal levels of plasma insulin, and both testosterone and androstenedione were demonstrated. Further, the severity of the acanthosis nigricans was directly related to the degree of hyperinsulinemia and was not correlated to the level of androgens. Our data suggest that the insulin resistance seen in obese acanthotic subjects cannot be attributed to hyperandrogenemia or obesity, since control subjects matched for severity of androgen excess or degree of obesity had much less insulin resistance.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism