Insulin Differences Between African-American and Caucasian Female Adolescents With Polycystic Ovary Syndrome (PCOS)

Summary

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PCOS is the most common endocrine abnormality of reproductive-aged women in the United States, affecting approximately 5 million women (1). The exact prevalence of PCOS in the adolescent population is unknown mainly attributed to the diagnostic challenge PCOS presents as the characteristics of norma...

PCOS is the most common endocrine abnormality of reproductive-aged women in the United States, affecting approximately 5 million women (1). The exact prevalence of PCOS in the adolescent population is unknown mainly attributed to the diagnostic challenge PCOS presents as the characteristics of normal puberty overlap with the signs and symptoms of PCOS (2). The key features of PCOS include menstrual irregularity, hyper¬androgenism, and polycystic ovarian morphology on ultrasound. However, clinical presentation may vary. It is a complex heterogeneous condition with life-long psychological, reproductive, and metabolic manifestations that impact a woman's health throughout her lifespan. PCOS is associated with major metabolic consequences including hyperinsulinism (i.e. increased insulin secretion), insulin resistance (i.e. decreased insulin sensitivity), obesity, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease, endothelial dysfunction, defective fibrino¬lysis, as well as endometrial carcinoma (3). Particular disease processes show a predilection for certain racial and ethnic groups. African-American [AA] adults are at increased risk of obesity, type 2 diabetes mellitus, cardiovascular disease mortality, and hyper¬tension compared to Caucasian [CA] adults. Past studies (4-9) have found that AAs have increased insulin secretion and decreased insulin sensitivity compared to their CA counterparts in adolescence and adulthood and even in childhood. These findings are secondary to the combination of increased insulin secretion and resistance with decreased insulin sensitivity and clearance noted in African-Americans. It is this combination of altered glucose metabolism that places AAs at increased risk of cardiovascular and metabolic morbidity. It has been proposed that hyperinsulinism or increased insulin secretion is a compensatory response by the pancreatic β-cell to increased insulin resistance. However, it has also been speculated that it is insulin resistance that is the compensatory response occurring in response to insulin hyper-secretion caused by pancreatic β-cell dysregulation (10-11). Hyperinsulinism and insulin resistance are known inherent features of PCOS. Several studies have demonstrated significant hyperinsulinism with insulin resistance and lowered insulin sensitivity in adolescents and adults with PCOS when compared to BMI-matched healthy control subjects (12-18). Marked differences in insulin sensitivity/resistance and PCOS phenotype have been reported in adults of different races/ethnicities with PCOS (19-23), however; other studies have refuted these claims (24-27). The objective of this study is to examine the differences in insulin secretion between AA and CA adolescents with PCOS. We will also examine differences in insulin sensitivity/resistance between AA and CA adolescents with PCOS. Primary Aim: To determine the influence of racial/ethnic background on insulin secretion in adolescent females with PCOS. Secondary Aim: To determine the influence of racial/ethnic background on insulin sensitivity/resistance in adolescent females with PCOS. Hypothesis: AA adolescent females with PCOS will have increased insulin secretion and decreased insulin sensitivity (i.e. increased insulin resistance) compared to CA adolescent females with PCOS. To address this hypothesis, we will utilize one of the gold standards endorsed by the American Diabetes Association that satisfactorily assess insulin secretion and insulin sensitivity/resistance. The method utilized in this study is the frequently sampled intravenous glucose tolerance test with minimal model analysis (MINMOD FSIVGTT) (28-32). Using the data that is gathered as part of our primary and secondary aims, we will also conduct an exploratory analysis to examine the influence of PCOS phenotype on insulin secretion and insulin sensitivity/resistance and the influence of racial/ethnic background on PCOS phenotype.

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