Racial and Ethnic Differences in the Metabolic Response of Polycystic Ovary Syndrome

Uche Ezeh; Yii-Der Ida Chen; Ricardo Azziz

Disclosures

Clin Endocrinol. 2020;93(2):163-172. 

In This Article

Abstract and Introduction

Abstract

Context: Polycystic ovary syndrome (PCOS) is a highly prevalent disorder associated with insulin resistance (IR) and compensatory hyperinsulinemia. Although variations in cardiometabolic risks across race and ethnicities have been reported in the general population, racial/ethnic disparities in the metabolic dysfunction of PCOS remain relatively unstudied.

Objectives: To determine whether markers of metabolic function differ in nondiabetic Asian American (AS), African American (AA), Hispanic White (HW), compared to non-Hispanic White (NHW) women with PCOS.

Design and Setting: Prospective cross-sectional study in a tertiary institution.

Participants and Interventions: A total of 259 nondiabetic women with PCOS (by NIH 1990 criteria) who completed a 2-hour 75-g oral glucose tolerance test measuring plasma glucose and insulin levels. Basal IR and insulin secretion, assessed by the homeostasis model assessment (HOMA-IR and HOMA-β%, respectively), and two-hour hyperglycaemia and hyperinsulinemia after an oral glucose load, were compared in 21 AS, 24 AA, 53 HW and 161 NHW consecutive nondiabetic adult PCOS women.

Results: After adjusting for age and body mass index, HW and AA PCOS women demonstrated higher fasting and post-glucose challenge insulin levels, and higher HOMA-IR and HOMA-β%, than NHW women, although glucose levels were similar. In contrast, AS PCOS women had or tended to have lower HOMA-β% than any other racial/ethnic groups, lower HOMA-IR, and fasting and post-challenge insulin levels than AA or HW, and also had higher (albeit still normal) mean post-challenge glucose levels than NHW women with PCOS despite similar HOMA-IR, and fasting insulin and post-challenge insulin levels. Waist-hip ratio was similar across the four groups.

Conclusion: Both HW and AA women with PCOS have increased basal state IR and higher β-cell response, and post-challenge hyperinsulinemia compared to NHW and AS subjects. The trend towards a lesser insulin response among Asian women requires further investigation. These findings suggest that the screening and management of metabolic dysfunction in PCOS should consider patients' race/ethnicity.

Introduction

The polycystic ovary syndrome (PCOS) is the most common endocrine-medical disorder in women, occurring in 10%-15% of reproductive-aged women.[1,2] PCOS is characterized by hyperandrogenism, oligo-ovulation and polycystic ovarian morphology, and is frequently associated with profound insulin resistance (IR) and compensatory hyperinsulinemia,[2,3] which increase the risk of type 2 diabetes mellitus (T2DM)[1–3] and risk factors for cardiovascular disease (CVD).[4] Over 80% of PCOS women manifest demonstrable IR and compensatory hyperinsulinemia[2,3] and approximately 31%-35% develop prediabetes and 7.5%-10% T2DM.[5,6]

In the United States, racial and ethnic health disparities are well documented. Hyperinsulinemia, IR, metabolic syndrome (MetSyn), T2DM, and CVD are more prevalent and more severe among African American (AA) and Hispanic White (HW), than non-Hispanic White (NHW) individuals, in the general US population.[7,8] However, less well documented is the impact of racial and ethnic differences on the metabolic dysfunction of PCOS. Previous studies have produced conflicting results. Some investigators have observed higher fasting insulin levels or IR values determined by the homeostasis model assessment (HOMA-IR), or higher prevalence of MetSyn among HW[9–11] and AA[12,13] women with PCOS, compared to those who are NHW. Alternatively, others have not observed such differences.[9,14–16] In another study, HW had higher fasting insulin levels and decreased basal state insulin sensitivity than Italian or Japanese women with PCOS, albeit the ethnic groups were studied in different countries by different investigators.[17] Little is known about differences in the metabolic dysfunction of PCOS by race or ethnicity assessed in the same population.

Several organizations recommend screening women with PCOS for T2DM using a standard 2-hour oral glucose tolerance test (OGTT) (eg Endocrine Society, American Association of Clinical Endocrinologists, Androgen Excess and PCOS Society, American College of Endocrinology and others).[18–20] However, while these recommendations vary according to body mass, among other factors, there has not been a consideration for the impact of ethnicity or race on the same.[20]

There has also been limited focus on understanding the degree of hyperinsulinemia, which is compensatorily increased in IR and drives much of androgen excess of PCOS.[21,22] In fact, evidence is emerging that postprandial hyperinsulinemia could be an important risk itself, determining cardiometabolic disease risks in the general population.[23] Several studies have suggested that hyperinsulinemia due to increased β-cell secretory capacity is a prominent feature in subjects of African ancestry,[8] although previous studies of racial/ethnic disparities in hyperinsulinemia in PCOS have focused on basal (unstimulated) insulin levels.[9–16]

Overall, it is unclear whether hyperinsulinemia under physiologic conditions differs by race/ethnicity in PCOS. Addressing racial/ethnic disparities in IR and hyperinsulinemia could be important in determining a more personalized approach to the management of metabolic dysfunction in women with PCOS and provide further insights into the cardiometabolic disease risks of these subjects. In the present study, we sought to begin to examine whether racial/ethnic differences exist in basal measures of insulin sensitivity and β-cell function, and in the post-challenge response of insulin to an oral glucose challenge, in nondiabetic women with PCOS.

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