The most common cause of insulin resistance and compensatory hyperinsulinemia is obesity, but despite its frequent occurrence in PCOS, obesity alone does not explain this important association (56). The insulin resistance associated with PCOS is not solely the result of hyperandrogenism based on the following: 1.
Hyperinsulinemia is not a characteristic of hyperandrogenism in general but is uniquely associated with PCOS (69).
2.
In obese women with PCOS, 30% to 45% have glucose intolerance or frank diabetes mellitus, whereas ovulatory hyperandrogenic women have normal insulin levels and glucose tolerance (69). It seems that the associations between PCOS and obesity on the action of insulin are synergistic.
3.
Suppression of ovarian steroidogenesis in women with PCOS with long-acting GnRH analogues does not change insulin levels or insulin resistance (70).
4.
Oophorectomy in patients with hyperthecosis accompanied by hyperinsulinemia and hyperandrogenemia does not change insulin resistance, despite a decrease in androgen levels (70,71).
Acanthosis nigricans is a reliable marker of insulin resistance in hirsute women. This thickened, pigmented, velvety skin lesion is most often found in the vulva and may be present on the axilla, over the nape of the neck, below the breast, and on the inner thigh (72). The HAIR-AN syndrome consists of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) (68,73). These patients often have high testosterone levels (>150 ng/dL), fasting insulin levels of greater than 25 μIU/mL (normal <20 to 24 μIU/mL), and maximal serum insulin responses to glucose load (75 gm) exceeding 300 μIU/mL (normal is <160 μIU/m: at 2 hours postglucose load).
The 2003 Rotterdam Consensus Group recommends that obese women with PCOS and nonobese PCOS patients with risk factors for insulin resistance, such as a family history of diabetes, should be screened for metabolic syndrome, including glucose intolerance with an oral glucose tolerance test (19). The standard 2-hour oral glucose tolerance test (OGTT) provides an assessment of both the degrees of hyperinsulinemia and glucose tolerance and yields the highest amount of information for a reasonable cost and risk (7).
Multiple other testing or screening schema were proposed to assess the presence of hyperinsulinemia and insulin resistance. In one, the fasting glucose-to-insulin ratio is determined, and values less than 4.5 indicate insulin resistance. Using the 2-hour GTT with insulin levels, 10% of nonobese and 40% to 50% of obese PCOS women have impaired glucose tolerance (IGT = 2-hour glucose level ≥140 but ≤199 mg/dL) or overt type 2 diabetes mellitus (any glucose level >200 mg/dL). Some research studies utilized a peak insulin level of over 150 μIU/mL or a mean level of over 84 μIU/mL over the three blood draws of a 2-hour GTT as a criteria to diagnoses hyperinsulinemia.