Obesity, Menstrual Irregularity and Polycystic Ovary Syndrome in Young Women With Type 1 Diabetes

A Population-Based Study

Eleanor P. Thong; Frances Milat; Anju E. Joham; Gita D. Mishra; Helena Teede

Disclosures

Clin Endocrinol. 2020;93(5):564-571. 

In This Article

Abstract and Introduction

Abstract

Background: Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications.

Objective: To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls.

Methods: Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989–95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self-reported menstrual irregularity, PCOS and BMI.

Results: Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m2, P < .001), where over half were overweight or obese (54.4% vs 32.9%, P < .001). Median BMI increased by 1.11 and 0.45 kg/m2, in the T1D and control groups, respectively. T1D was independently associated with an increased risk of menstrual irregularity (RR 1.22, 95% CI 1.02–1.46) and PCOS (RR 2.41, 95% CI 1.70–3.42). Obesity conferred a 4-fold increased risk of PCOS, compared to those with normal BMI (RR 3.93, 95% CI 3.51–4.42).

Conclusions: Obesity is prevalent amongst women with T1D and may be a key contributor to the higher risk of menstrual irregularity and PCOS in this cohort, representing an important opportunity for prevention and intervention.

Introduction

Type 1 diabetes mellitus (T1D) is a chronic autoimmune condition with a peak incidence in childhood and adolescence worldwide.[1] In Australia, 61% of all new diagnoses of T1D in 2017 occurred in individuals under the age of 25, where the peak age of diagnosis was between 10 to 14 years.[2] The onset of T1D at an early stage in the lifespan, particularly at a prepubertal age, has ramifications on the gonadotrophic axis and ovarian function, with as many as 40% of females with T1D exhibiting menstrual and reproductive disorders.[3] Reproductive disturbance is therefore common in young women with T1D, encompassing a spectrum of menarchal delay, oligomenorrhea, polycystic ovary syndrome (PCOS) and early menopause.

Perturbations of the hypothalamic-pituitary-ovarian axis have been described in individuals with T1D.[3–5] While the mechanisms for reproductive disturbance in T1D are not well understood, multiple factors are likely to contribute to the overall pathogenesis. Insulin plays an important role in the regulation of ovarian function and the gonadotrophic axis. Insulin deficiency decreases pituitary gonadotrophin-releasing hormone (GnRH) stimuli, leading to a reduction in gonadotrophin secretion and ovarian steroid production.[4,6] Hyperglycaemia exerts gluco-toxic effects on the ovaries directly or indirectly via advanced glycation end-products and their receptors.[7,8] Prior to the advent of insulin therapy, the majority of patients with T1D failed to thrive and exhibited profound hypogonadism, with severe pubertal delay, amenorrhoea and infertility.[3] The discovery and introduction of insulin therapy in 1922 led to improved metabolic control, which ameliorated amenorrhoea and subfertility in women with T1D.[9] However, up until the late 1980s, menstrual disturbance and menarchal delay were highly prevalent, predominantly in women diagnosed with T1D before puberty.[10,11] In 1993, the landmark Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the benefits of intensive insulin treatment, comprising three or more daily injections of insulin or pump therapy, on the onset and progression of long-term diabetic microvascular sequelae.[12] With enhanced metabolic control, menarchal delay is now uncommon in girls with T1D,[13,14] although oligomenorrhea continues to persist in 25%-35%[15–17] of adolescent girls and around 20%[18,19] of adult women with T1D. Menstrual irregularities in this cohort have been associated with poorer glycaemic control and weight gain.[15,20]

Importantly, there has been an emergence of polycystic ovary syndrome (PCOS) in T1D over the last two decades. In 1994, Adcock and colleagues found that over two-thirds of postmenarchal girls with T1D who had irregular menses, exhibited polycystic ovarian morphology.[20] Escobar-Morreale and colleagues reported a high prevalence of hyperandrogenism and PCOS in women with T1D,[21] and since then, several other studies[22,23] have confirmed these findings, where the pooled prevalence of PCOS in a recent meta-analysis was reported to be 24% in women with T1D,[21] compared to 8%-13% in the general population.[24,25] The emergence of PCOS appears to mirror the increase in obesity rates over the last few decades, in this cohort. Obesity and PCOS appear to have a bidirectional interaction, each significantly exacerbating the other condition.[26–28] Few studies have explored the contribution of weight gain, overweight and obesity to menstrual disturbance and PCOS in this cohort. Therefore, we sought to evaluate the relationships between BMI on menstrual irregularity and PCOS, respectively, in young women with T1D.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....