Prospective Studies of Risk Factors Associated with Type 2 Diabetes, Cardiovascular Disease, and Mortality in Elderly Women

The world’s population is ageing. With an increased life expectancy across the globe, more people will live into old age. Women outlive men averagely by four years, warranting an increased focus on healthy ageing in women. The demographic shift resulting in an increased fraction of elder individuals has given rise to concerns about whether the extra life years added are spent in good health or with disease conditions resulting in high impacts on health care systems, socioeconomic relations and on the individual level. The World Health Organization predicts the burden of non-communicable diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) to account for more than three-fourths of the total disease burden in middle and high-income countries before year 2030. Despite the identification of many risk factors for non-communicable diseases within the last decades, these risk factors remain the leading contributors to decreased healthy life expectancy in late-life, necessitating an increased focus on risk factors and non-communicable diseases specifically in elderly.

The studies constituting the foundation of this thesis aim to explore hypotheses focusing on known and novel risk factors and their relation to ageing, disease, and mortality in elderly Danish women. The studies are epidemiological in their character and based on data from the Prospective Epidemiological Risk Factor (PERF) study, a community-based cohort study on 5,855 elderly Danish women enrolled in year 2000 with a follow-up examination of 2,103 of the women in year 2013 (study I).

Data from the PERF cohort was used to evaluate whether the metabolic syndrome (MetS), a cluster definition of cardio-metabolic risk factors, is a valid and useful tool for prediction of future T2DM and CVD specifically in elderly women (study II). The study described how women fulfilling the current MetS criteria set by the International Diabetes Federation revealed an increased risk of future T2DM or CVD diagnosis. However, subjects who did not fulfil the definition criteria for MetS, but presented one or more of the MetS risk factors were likewise at increased risk. A further subdivision of the control group showed to increase the risk of T2DM to 6.3-fold (from 3.6-fold) and 1.7-fold for CVD (from 1.3-fold) for MetS-defined women when compared specifically to a control group solely including women with no MetS risk factors.Based on these risk estimates, it was concluded that employment of the MetS in elderly women should be focused only as a tool for identifying subjects with metabolic high-risk profiles. Further, the sum of risk factors was proposed to be equally considered, as elderly women holding only a few MetS risk factors, were also at increased risk of T2DM and CVD.

The cohort was further used to explore how weight and weight change in late-life affected the risk of hyperglycaemia in elderly women (study III). The study presented a 2-fold increased risk of hyperglycaemia in overweight and obese elderly women compared to normalweight women after 13 years. In women who gained weight, the risk of hyperglycaemia in late-life was most profound for overweight and obese women resulting in a 2.7-fold increased risk of hyperglycaemia in overweight weight gainers and a 3.2-fold increased risk in obese weight gainers compared to normalweight weight-stable women. Contrarily, overweight and obese women who lost weight during the follow-up period decreased their risk of hyperglycaemia to a level comparable to women who stayed normalweight during the follow-up period.

The thesis rounds off by introducing a novel risk factor; matrix metalloproteinase (MMP)- mediated degradation of collagen type I (C1M) that was used in the description of mortality in elderly women (study IV). The study showed how increased MMP-mediated tissue degradation, as an independent risk factor, was associated with a 2-fold increase in all-cause mortality within three years of follow-up and a 1.5-fold increase in all-cause mortality up to nine years prior to death.

Overall, these studies contribute to the knowledge specifically demanded on women’s health in late-life by describing associations between known risk factors of the MetS and subsequent risk of T2DM and CVD. Further, by highlighting associations between hyperglycaemia, weight and weight change in late-life, and lastly by the evaluation of collagen type I degradation possibly being an important predisposition for increased mortality in elderly women.