Our first specific aim in an observational study of 431 nondiabetic women with
polycystic ovary syndrome (PCOS), aged >or=20 years and with >or=11 months follow-up on
metformin diet, was to prospectively assess relationships between pretreatment
glucose and
insulin resistance (IR) and the development of
type 2 diabetes mellitus (T2DM) or
gestational diabetes (GD). Our second specific aim was to determine whether development of T2DM and GD was independently associated with lesser reduction of IR on
metformin diet when compared with women who remained free of T2DM and GD. Women with body mass index <25 kg/m(2) and those with body mass index >or=25 kg/m(2) were, respectively, instructed in a 2000- or 1500-cal/d, high-
protein (26% of calories), low-
carbohydrate (44%) diet, with 30% of calories as fat and a polyunsaturate-saturate ratio of 2:1. Three groups of women with PCOS were categorized: (
a) 17 with no previous GD, who developed T2DM on
metformin diet (mean +/- SD follow-up, 49 +/- 33 months), (b) 401 with no previous GD and free of T2DM on
metformin diet (follow-up, 38 +/- 25 months), and (c) 13 with either previous GD or GD on
metformin diet (follow-up, 38 +/- 25 months). On
metformin diet, women who developed T2DM vs those who remained free of T2DM had higher pretreatment
glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.16; P = .003) and homeostasis model assessment of
insulin resistance (HOMA-IR) (OR, 1.22; 95% CI, 1.04-1.42; P = .01), and less reduction of HOMA-IR (OR, 0.82; 95% CI, 0.72-0.92; P = .0008). On
metformin diet, women either with previous GD or who developed GD vs those who remained free of T2DM had less reduction of HOMA-IR (OR, 0.88; 95% CI, 0.78-0.99; P = .03). By repeated-measures analysis, on
metformin diet, women who did not develop T2DM had reduction in HOMA-IR (P < .0001), with the slope of this curve different (P = .002) from the unchanged IR exhibited by women who developed T2DM and different (P = .017) from an increased IR slope (P = .049) in women who had GD. In women with PCOS, pretreatment
glucose and IR, and lesser reduction in IR on
metformin diet were associated with T2DM and GD.