The documentation of hyperinsulinemia using either the glucose to insulin ratio or the 2-hour GTT with insulin is problematic. When compared to the gold standard measure for insulin resistance, the hyperinsulemic-euglycemic clamp, it shows that the glucose-to-insulin ratio does not always accurately portray insulin resistance. When hyperglycemia is present, a relative insulin secretion deficit is present. This deficient insulin secretion exacerbates the effects of insulin resistance and renders inaccurate the use of hyperinsulinemia as an index of insulin resistance. Thus, routine measurements of insulin levels may not be particularly useful.
Although detection of insulin resistance, per se, is not of practical importance to the diagnosis or management of PCOS, testing women with PCOS for glucose intolerance is of value because their risk of cardiovascular disease correlates with this finding. An appropriate frequency for such screening depends on age, BMI and waist circumference, all of which increase risk.
Two-Hour Glucose Tolerance Test Normal Glucose Ranges (World Health Organization criteria, after 75-gm glucose load)
Fasting 64 to 128 mg/dL
One hour 120 to 170 mg/dL
Two hour 70 to 140 mg/dL
Two-Hour Glucose Values for Impaired Glucose Tolerance and Type 2 Diabetes (World Health Organization criteria, after 75-gm glucose load)
Impaired (2-hour) = 140 to 199 mg/dL
Abnormal glucose metabolism may be significantly improved with weight reduction, which may reduce hyperandrogenism and restore ovulatory function (74). In obese, insulin-resistant women, caloric restriction that results in weight reduction will reduce the severity of insulin resistance (a 40% decrease in insulin level with a 10-kg weight loss) (75). This decrease in insulin levels should result in a marked decrease in androgen production (a 35% decrease in testosterone levels with a 10-kg weight loss) (76). Exercise reduces insulin resistance, independent from any associated weight loss, but data on the impact of exercise on the principal manifestations of PCOS are lacking.
In addition to addressing the increased risk for diabetes, the clinician should recognize insulin resistance or hyperinsulinemia as a cluster syndrome called metabolic syndrome or dysmetabolic syndrome X. Recognition of the importance of insulin resistance or hyperinsulinemia as a risk factor for cardiovascular disease led to diagnostic criteria for the dysmetabolic syndrome. The more dysmetabolic syndrome X criteria are present, the higher the level of insulin resistance and its downstream consequences. The presence of three of the following five criteria confirm the diagnosis, and an insulin-lowering agent and/or other interventions may be warranted (19).
Fasting glucose: 110–126 mg/dL
Two-hour glucose (75 gm OGTT): 140–199 mg/dL
Risk factors for the dysmetabolic syndrome include nonwhite race, sedentary lifestyle, BMI greater than 25, age over 40 years, cardiovascular disease, hypertension, PCOS, hyperandrogenemia, insulin resistance, HAIR-AN syndrome, nonalcoholic steatohepatitis (NASH), and a family history of type 2 diabetes mellitus, gestational diabetes, or impaired glucose tolerance.
Comprehensive treatment of PCOS addresses reproductive, metabolic and psychological features.