Normal metabolic flexibility despite insulin resistance in lean and obese women with polycystic ovary syndrome
Marek Straczkowski, Irina Kowalska, Agnieszka Adamska, Monika Karczewska-Kupczewska, Agnieszka Nikolajuk, Agnieszka Lebkowska & Maria Gorska
Polycystic ovary syndrome (PCOS) is heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance is associated with the so-called metabolic inflexibility i.e. an impaired switch from lipid to glucose in response to insulin. The aim of the present study was to estimate glucose and lipid oxidation, metabolic flexibility and non-oxidative glucose metabolism in lean and obese PCOS patients.
The study group consisted of 72 women with PCOS (28 lean and 44 overweight or obese) and 26 healthy, normally menstruating women (13 lean and 13 overweight or obese). Euglycemic hyperinsulinemic clamp and the measurements of serum sex hormones were performed. Glucose and lipid oxidation was evaluated with indirect calorimetry in the baseline state and during the last 30 min of the clamp. Non-oxidative glucose metabolism in the hyperinsulinemic state was calculated by subtracting glucose oxidation from the total glucose metabolism. Metabolic flexibility was assessed as an increase in respiratory quotient (ΔRQ) in response to insulin. To evaluate the impact of obesity and PCOS on the studied parameters and the interaction between both conditions, general linear models were constructed.
Both PCOS (P<0.0001) and obesity (P=0.0045) were associated with lower insulin sensitivity. No significant interaction between PCOS and obesity was found. Similarly, PCOS (P=0.00078) and obesity (P=0.009) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.0097) and higher lipid oxidation (P=0.0001) in insulin-stimulated conditions whereas PCOS had no effect on these parameters. Metabolic flexibility was impaired in obese (P=0.0015) but not in PCOS women.
Our data indicate that lean and obese PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.