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Aims To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. Methods A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25·4%) patients died of which 66 (15·2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. Results Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. Conclusions Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.