Normal metabolic flexibility despite insulin resistance women with polycystic ovary syndrome
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland. Endocrine Journal
(Impact Factor: 2).
06/2013; 60(9). DOI: 10.1507/endocrj.EJ13-0115
Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg x m(-2)) and 52 overweight or obesity (BMI>25 kg x m(-2)), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.
Available from: Steven Lindheim
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ABSTRACT: Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.
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ABSTRACT: Polycystic ovary syndrome (PCOS) affects between 4%-18% of reproductive-aged women and is associated with increased risk of obesity and obesity-related disease. PCOS is associated with hyperinsulinemia, which is known to impair fat oxidation. Research shows that carbohydrates from dairy and starch-based foods cause greater postprandial insulin secretion than carbohydrates from nonstarchy vegetables and fruits. The purpose of this study was to determine whether an ad libitum 8-week low-starch/low-dairy diet would improve fasting and postprandial fat oxidation after a high saturated fat liquid meal (HSFLM) in overweight and obese women with PCOS. Prospective 8-week dietary intervention using a low-starch/low-dairy diet in 10 women (body mass index ≥25 kg/m(2) and ≤45 kg/m(2)) with PCOS. Indirect calorimetry was used at fasting and for 5 h following consumption of the HSFLM to determine respiratory exchange ratio (RER), macronutrient oxidation, and energy expenditure (EE) at week 0 and week 8. Participants had a reduction in body weight (-8.1 ± 1.8 kg, p < 0.05) and fasting insulin (-19.5 ± 8.9 μg/mL, p < 0.05) after dietary intervention; however, these were not significantly correlated with improved fat oxidation. There was a reduction in fasting RER, and fasting and postprandial carbohydrate oxidation, and an increase in fasting and postprandial fat oxidation after adjusting for body weight. There was also significant difference in incremental area under the curve from pre- to post-diet for fat (0.06 ± 0.00 g/kg per 5 h; p < 0.001) and carbohydrate oxidation (-0.29 ± 0.06 g/kg per 5 h; p < 0.001), but not for RER or EE. In conclusion, an 8-week low-starch/low-dairy diet increased fat oxidation in overweight and obese women with PCOS.
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