Perry, Ivan J.; (1996) Non-insulin-dependent diabetes and coronary heart disease in middle-aged men. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis addresses the aetiology of non-insulin dependent diabetes (NIDDM) and the association between NIDDM and coronary heart disease (CHD). Hypotheses regarding the causal role of obesity, physical inactivity, alcohol consumption and cigarette smoking in the development of NIDDM have been tested. The hypothesis that NIDDM shares common risk factors with coronary heart disease, factors which are associated with insulin resistance has also been addressed. Associations between lifestyle and biological CHD risk factors and the risk of developing NIDDM were examined in a longitudinal study, involving a representative sample of 7735 middle-aged British men, followed for an average of 12.8 years. In a cross-sectional study, associations between baseline non-fasting serum insulin levels and CHD risk factors were examined in 5556 men. In further longitudinal studies, insulin levels at baseline were related to the subsequent development of both NIDDM and major CHD events and associations between both established NIDDM and non-fasting serum glucose and incident major CHD events in this cohort were also examined. There were 194 new cases of NIDDM in the longitudinal study. Obesity and physical inactivity were associated with higher risk and moderate alcohol intake with lower risk of NIDDM (relative to occasional drinkers) in multivariate analysis. Men destined to develop NIDDM during follow-up had an adverse coronary risk factor profile at baseline. However some important CHD risk factors, notably serum total cholesterol concentration did not predict NIDDM and the effect of cigarette smoking was equivocal. In cross-sectional analyses, CHD risk factors such as physical inactivity and hypertriglyceridaemia, which were predictive of NIDDM in the longitudinal study, were associated with hyperinsulinemia at the baseline examination. A J-shaped relation between serum insulin levels and risk of NIDDM was observed which is consistent with an early and fundamental role for insulin resistance in the development of this condition. Established NIDDM was associated with an approximately 2-fold increased risk of CHD events during follow-up. independent of other CHD risk factors. In non-diabetics, a weak non-linear association between non-fasting glucose and incident CHD events (N=704) was observed which was non-significant in multivariate analysis. A similar non-linear association between serum insulin concentration at screening and major CHD events during follow-up was observed. There was an almost 2-fold increased relative risk of major CHD events in the l0th decile of the serum insulin distribution relative to the 1st to the 9th deciles combined which was significant in multivariate analysis. The findings support the hypothesis that non-insulin dependent diabetes and coronary heart disease share common lifestyle and biological risk factors which are associated with hyperinsulinemia and insulin resistance. There is however a major component of CHD risk which is not related to insulin resistance and diabetes.

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