Role of alcohol and smoking for vascular complications in type 1 diabetes

Background Moderate alcohol consumption is associated with a decreased risk of coronary heart disease (CHD). However, the association between alcohol and microvascular disease entities is less studied and largely unclear. Previous studies have linked smoking with an increased risk of micro- and macrovascular complications in people with type 1 diabetes. However, these studies have often combined current and former smokers and neglect the effect of smoking cessation. In addition, most previous studies have not included dose-dependent measures of smoking. Aims The aim of this thesis was to study the effect of alcohol consumption on the risk of diabetic nephropathy and severe diabetic retinopathy in people with type 1 diabetes. The effect of smoking on the development of diabetic nephropathy, CHD, and stroke was also addressed. In addition, the combined effect of smoking and a known genetic variant on the development of the end-stage renal disease (ESRD) was investigated. Subjects and methods All people included in the study were participants in the ongoing nationwide, multicenter Finnish Diabetic Nephropathy Study (FinnDiane), the aim of which is to identify risk factors of vascular complications in people with type 1 diabetes. This thesis is based on four studies. Study I (n=3608) is cross-sectional in nature and Study II (n=3613), Study III (n=2621), and Study IV (n=4506) are prospective. Information regarding micro- and macrovascular complications is based on data from FinnDiane visits and national data from the Finnish Care Register for Health Care and the Cause of Death Register. Results Compared with light consumers, people who have never consumed alcohol have a higher risk of both diabetic nephropathy and severe diabetic retinopathy. People who have given up using alcohol have the highest risk of diabetic nephropathy and retinopathy. The risk of diabetic nephropathy is increased in spirit-drinking men, and the risk of severe diabetic retinopathy is increased in all spirit drinkers compared with wine drinkers. Compared with never smokers, current smokers have a higher risk of diabetic nephropathy. Former smokers have a similar risk of diabetic nephropathy compared to never smokers. Compared with never smokers, current smokers have an increased risk of CHD, heart failure, and stroke, and former smokers have an increased risk of heart failure in the whole study population and an increased risk of stroke in men. In both current and former smokers, the risk of each cardiovascular event increases with increasing cumulative smoking and increasing intensity of smoking. The rare variant of allele rs4972593, previously known to increase the risk of ESRD in women, is associated with a decreased risk of ESRD in non-smoking men. Conclusions Abstaining from alcohol or previous alcohol consumption and the consumption of spirits are associated with a higher risk of diabetic nephropathy and severe retinopathy. Current smoking is associated with a higher risk of diabetic nephropathy, CHD, heart failure and stroke in a dose-dependent manner. After smoking cessation, the risk of diabetic nephropathy and CHD is decreased and approaches the risk seen in never smokers. However, the risk of heart failure and stroke remains higher in former smokers. Contrary to the previous findings in women, the rare allele rs4972593 seems to have a protective effect in relation to the risk of ESRD in men.