Insulin resistance in reproductive aged women

Abstract

Overweight and obesity rates are consistently increasing worldwide. Many countries, including Australia report higher increases in obesity rates in women compared to men. In particular, weight gain in younger, reproductive aged women is escalating. Obesity, being an insulin resistant state, has serious health consequences. Traditionally, the focus has been on type II diabetes and cardiovascular disease in older individuals. However, in women of reproductive age, adverse lifestyle, obesity and insulin resistance has significant reproductive health implications that often occur well before type II diabetes. These include polycystic ovary syndrome and gestational diabetes mellitus in pregnancy. With high rates of weight gain and clear complications, young women present an important target group for intervention strategies. Insulin resistance is challenging to assess and relevant literature and novel new methods are explored early in the thesis. I then aimed to explore the role of lifestyle change and increased physical activity in two groups of overweight reproductive aged women with insulin resistance; women with polycystic ovary syndrome (PCOS) and pregnant women at high risk for developing gestational diabetes mellitus (GDM). As lifestyle improvement including exercise is highly effective in alleviating insulin resistance in other high risk groups, the studies presented in this thesis have a focus on promoting and evaluating healthy lifestyle and physical activity as a primary theme. I performed an extensive systematic literature review which highlighted research gaps and set the context for our intervention study in PCOS. In a comprehensive mechanistic study in overweight women with and without PCOS, intensified exercise training was evaluated without specified dietary prescription over 12 weeks. I assessed the effects on the key outcome measures; insulin resistance and body composition. This comprehensive study demonstrated worsened insulin resistance in PCOS women compared to non-PCOS control women. Following exercise, insulin resistance improved in both groups without change in weight suggesting the value of exercise in PCOS exceeds its impact on weight alone. Reproductive function also improved with exercise in PCOS women. Women with PCOS showed reduced visceral fat following exercise which is linked to insulin resistance; with no change in the control group. Despite reduced levels of visceral fat and improved insulin resistance, women with PCOS still had greater insulin resistance following exercise in comparison to controls. This study advanced the understanding of insulin resistance in PCOS but also highlighted the need to further mechanistically explore intrinsic insulin signalling defects in PCOS and evaluate the role of exercise in PCOS. In a large randomised controlled public health trial with overweight and obese pregnant women at risk for GDM, a healthy lifestyle program promoting increased physical activity, behaviour change and simple key messages related to improving diet was applied from early pregnancy to six weeks postpartum to assess key outcome measures including gestational weight gain, GDM incidence and physical activity levels. Pregnant women at increased risk for GDM were identified by the development and implementation of a risk screening tool. This Healthy Lifestyle Program (HeLP-her) in pregnancy study is modified from a previously successful intervention in mothers of school children developed by my supervisors and is set in a hospital setting. We have successfully recruited over 200 women (May 2008 – Oct 2010), with 166 of these having completed final data collection. The study is currently ongoing however interim results are presented in this thesis. I have investigated optimal measurement of physical activity in pregnancy, confirming the accuracy of pedometers in this setting. In the setting of a randomised controlled trial with the results of intervention still to be revealed, I have evaluated key lifestyle behaviours in women during pregnancy in the control group not receiving the intervention; drawing on key characteristics of women recruited for this study, describing early pregnancy weight gain, early pregnancy health behaviours and GDM incidence. Results to date demonstrate excess weight gain, a high GDM prevalence and sedentarism in early- to mid- pregnancy, highlighting the urgent need for lifestyle intervention in this high-risk group. The studies presented in this thesis add significantly to the literature, in young, insulin resistant women. The findings provide further evidence that lifestyle change incorporating increased physical activity is important for targeting insulin resistance, particularly in overweight women with PCOS. Final results are pending for lifestyle intervention in women at risk for GDM; however results to date demonstrate increased weight gain in early pregnancy and development of adverse health as evident by a high GDM incidence, mandating increased public health action towards improving lifestyle in this high-risk group. I have successfully finalised recruitment and await the results from the GDM intervention trial which will allow future clarification of the role of lifestyle change in overweight and obese insulin resistant pregnancies. Our group is building on the work presented in this thesis and has successfully obtained NHMRC funding to extend the intensified exercise training program in PCOS women to explore the effects in lean PCOS women. Additionally, we have also adapted the healthy lifestyles program to other populations at-risk, including women with PCOS, those with diabetes and high-risk ethnic subgroups. The findings presented in this thesis have made a significant contribution to women’s health, in settings where insulin resistance is present, creating an evidence base for the importance of lifestyle change in insulin resistant, reproductive aged women.