Development of type 2 diabetes in adolescent girls with polycystic ovary syndrome and obesity

Abstract

Objective: Adult women with polycystic ovary syndrome (PCOS) and obesity have an 8-fold increased risk of developing type 2 diabetes (T2D). Our goal was to determine the incidence and risk factors for T2D in adolescents with PCOS and obesity.Research design and methods: Retrospective chart review of girls aged 11-21 years with confirmed PCOS (oligomenorrhea and hyperandrogenism) diagnosis between July 2013 and Aug 2018 and at least one follow-up visit and BMI >85%ile. T2D incidence, defined with an HbA1c ≥6.5%, was calculated. A nested case-control study with 1:3 matching by race, ethnicity, and BMI was performed to determine predictors of T2D diagnosis.Results: Four hundred ninety-three patients with PCOS (age 15.6 ± 1.9 years, BMI 36.2 ± 6.3 kg/m 2 ) were identified with a follow-up of 1018 person-years. Twentythree developed T2D (incidence 22.6/1000 person-years) with diagnosis a median of 1.8 years (2 months-5.5 years) after PCOS diagnosis. T2D risk was higher in girls with a prediabetes HbA1c (5.7%-6.4%) ) and among Hispanic girls with an elevated HbA1c and alanine aminotransferase ) at the time of PCOS diagnosis. In the 1:3 matched cohort, T2D risk was 18.7 times higher ) for every 0.1% increase in HbA1c at the time of PCOS diagnoses.Conclusions: Girls with PCOS and obesity have an 18-fold increase in T2D incidence compared to published rates in non-PCOS youth. Hispanic girls with elevated HbA1c and ALT are at particular risk. Due to the morbidity associated with youth onset T2D, these findings argue for better screening and prevention approaches in this population.

Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

“…There is evidence that dysglycemia and HS are present early in PCOS, especially in girls with obesity. For instance, we found that 32% of adolescents with PCOS and obesity showed evidence of dysglycemia (22). Additionally, the incidence rate of developing T2D was up to 22‐fold higher in girls with PCOS; those at highest risk of developing T2D had evidence of prediabetes and HS at the time of PCOS diagnosis (22).…”

“…The lack of association among this cohort of relatively healthy girls with obesity may reflect an early disease state and it is also similar to what has previously been shown in youth (8,10). Whereas adolescents with PCOS have a 22‐fold increased risk of developing T2D, our analysis only included girls without diabetes (22). A cohort including girls with worse pancreatic dysfunction and dysglycemia may demonstrate a stronger relationship between androgens and PFF.…”

“…For instance, we found that 32% of adolescents with PCOS and obesity showed evidence of dysglycemia (22). Additionally, the incidence rate of developing T2D was up to 22‐fold higher in girls with PCOS; those at highest risk of developing T2D had evidence of prediabetes and HS at the time of PCOS diagnosis (22). Another study including 163 girls with PCOS and varying BMI z scores identified abnormal glucose metabolism in 17.2% of the cohort (16.0% with impaired glucose tolerance, 1.2% with T2D) (35).…”

“…Increased rates of dysglycemia also are documented in both fasting and postprandial tests (19‐21). Furthermore, we recently demonstrated that dysglycemia was one of the best predictors for development of T2D in girls with obesity and PCOS (22). However, to our knowledge, there is a gap in the literature regarding the association between PFF and insulin sensitivity and secretion in adolescents with PCOS and obesity.…”

Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome but Affects Amino Acid Metabolism in Sera of Obese Girls With Polycystic Ovary Syndrome

“…( Teede et al, 2018 ) The diagnosis of POCS in adolescents is based on the presence of menstrual irregularity for gynecological age and clinical (i.e., hirsutism or severe acne) or biochemical hyperandrogenism ( Teede et al, 2018 ; Peña et al, 2020 ) Apart from the reproductive dysfunction of PCOS, several metabolic comorbidities are thought to either exacerbate or drive the development of PCOS, including obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD), albeit mechanisms have not been clearly delineated. Metabolic co-morbidities develop early; adolescents with PCOS and obesity have an 18-fold higher incidence of developing type 2 diabetes ( Hudnut-Beumler et al, 2021 ), a prevalence of NAFLD of 40–60%% ( Carreau et al, 2019 ; Andrisse et al, 2021 ). Understanding the unique etiologies of PCOS which manifest in adolescence and their respective biomarkers are needed for early, effective interventions to prevent or mitigate such deleterious health outcomes.…”