Patients with PCOS likely to develop IFG, combined glucose intolerance

Despite having severe hyperinsulinemia, patients with polycystic ovary syndrome are likely to develop impaired fasting glucose and combined glucose intolerance, new data suggested.

The patients who develop IFG and combined glucose intolerance demonstrate comparable insulin resistance but dissimilar response patterns, according to the researchers.

For the study, 143 patients with PCOS underwent oral glucose tolerance testing and 68 had frequently sampled IV glucose tolerance tests. Researchers measured changes in plasma glucose, insulin, cardiovascular risk factors and androgens.

Patients with IFG and combined glucose intolerance were significantly insulin resistant compared with patients with normal glucose tolerance (homeostasis model assessment: 3.3 for normal glucose tolerance vs. 6.1 for IFG and 6.4 for combined glucose intolerance; P<.0001). These patients were also significantly hyperinsulinemic (insulin area under the curve for 120 minutes: 973 pmol/L for normal glucose tolerance vs. 1,470 pmol/L for IFG and 1,461 pmol/L for combined glucose intolerance; P<.0001).

Patients with combined glucose intolerance exhibited a greater delayed insulin response compared with patients with IFG (two hour OGTT results: 1,001 pmol/L vs. 583 pmol/L; P<.0001).

Compared with patients with normal glucose tolerance, those with combined glucose intolerance had a lower disposition index (1,615 vs. 987; P<.0234) and adiponectin level (11.1 ng/mL vs. 6.2 ng/mL; P<.0096). Also, compared with the normal glucose tolerance group, patients with IFG had a reduced insulinogenic index (268 vs. 421; P<.05).

The resistant tertile of the normal glucose tolerance group had elevated triglycerides and high-sensitivity C-reactive protein and decreased HDL and sex hormone-binding globulin vs. the insulin-sensitive tertile. Triglyceride, C-reactive protein and free androgen index levels were directly correlated with insulin resistance in the entire population and inversely correlated with sex hormone-binding globulin.

“We propose the natural course of glucose intolerance in PCOS as follows: Insulin resistance increases with weight gain, as suggested by the stepwise increase in BMI in the normal glucose tolerance tertiles; as long as insulin response can compensate, plasma glucose remains within the ‘normal’ range; a relatively small decrease in overall insulin response results in isolated IFG; a decrease in the early insulin response results in impaired glucose tolerance/combined glucose intolerance, even with late hyperinsulinemia,” the researchers said. “Factors leading to impairment of the early vs. overall response are not known, although genetic factors may be important.”

Karakas SE. Diabetes Care. 2010;33:887-893.