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Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance

Abstract

Purpose

Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders).

Methods

22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC2h-insulin during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp.

Results

Women with PCOS showed significantly higher levels of AUC2h-insulin (p < 0.011), Insulinogenic Index (p < 0.001), DIo (p = 0.002) and significantly lower levels of AUC2h-glucose (p = 0.001). No difference was found between the two groups regarding insulin sensitivity (M value). Lower levels of MCRI were found in women with PCOS [420 (IQR 227–588) vs. 743 (IQR 597–888) ml m−2 min−1: p < 0.001]. Furthermore, in the PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC2h-insulin (PCOS: β:−0.878; p < 0.001; Prediabetes: β:−0.501; p = 0.019).

Conclusions

Our study suggests that in normoglycemic women with PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined “compensatory”; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.

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Acknowledgments

M. C. Amato—deceased.

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Correspondence to C. Giordano.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Amato, M.C., Vesco, R., Vigneri, E. et al. Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance. J Endocrinol Invest 38, 1319–1326 (2015). https://doi.org/10.1007/s40618-015-0372-x

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  • DOI: https://doi.org/10.1007/s40618-015-0372-x

Keywords

  • PCOS
  • Insulin clearance
  • Clamp
  • Hyperinsulinism
  • Insulin resistance