Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome

Abstract

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese (n = 19) and nonobese (n = 10) PCO women and age- and body-composition-matched normal ovulatory women (n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP (P less than .05). Steady-state insulin levels of approximately 100 microU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight (P less than .001) or per kilogram fat free mass (P less than .001) or when divided by the steady-state plasma insulin (l) level (M/l, P less than .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4) PCO is associated with a unique disorder of insulin action.

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study

“…In addition to abnormal morphology of the ovary [7], increased ovarian production of androgens [8], hyperinsulinemia. is present in about 80% of obese women with PCOS [9] and 50-70% of all women with PCOS [10].Hyperinsulinemia and insulin resistance may contribute to increased risk of developing type II diabetes, hypertension and the adverse cardiovascular risk [11]. Hyperinsulinemia is more strongly associated with anovulation than any other feature of the syndrome.…”

Luteal-phase inhibin A and follicular-phase inhibin B levels are not characteristic of patients with an elevated LH-to-FSH ratio

“…The most common cause of normogonadotropic normoestrogenic ovulatory disorders (constituting the so-called WHO 2 group) is polycystic ovary syndrome (PCOS), characterized by chronic anovulation, hyperandrogenism [2], and often by hyperinsulinemia [3].…”

Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects

“…Moreover, it has been previously shown in PCOS women that obesity (i.e. BMI status) was a significant modifier of the relationship between PCOS status and many metabolic parameters [8,35]. Thus, we performed multiple linear regression analyses for all variables in Table 1 with group status, BMI status and the interaction between group status and BMI status as independent parameters.…”

“…Indeed, obese and lean women with PCOS display insulin resistance independently of BMI [3,4,8], and administration of insulin-sensitising drugs such as metformin [3,4], troglitazone [3,4], or D-chiro-inositol [9,10] to both obese and lean women with PCOS increases the frequency of ovulation and decreases circulating androgens.…”