The Role of a CA Repeat Polymorphism in the Promoter Region of the Insulin like Growth Factor-I gene in Physiology and the Pathophysiology of Diabetes Mellitus

textabstractA polymorphism in the promoter region of the IGF-I gene is amongst others related to total IGF-I serum levels, body height and type 2 diabetes. In this thesis, we investigated the influence of this polymorphism on the age-related decline, secular trend in body height, beta cell function, risk of micro-albuminuria, diabetic retinopathy and mortality. All subjects were participants of the Rotterdam Study, a population based cohort study of diseases in the elderly. We observed an age related decline in IGF-I serum levels only in subjects who were carrier of the most frequent alleles. Individuals who were non-carriers of the most frequent alleles, had the lowest serum IGF-I level and the lowest body height. Furthermore, we observed in this group in individuals with a normal glucose tolerance a decreased beta cell function. Non-carriers of the mst freqent alleles also had a higher risk to develop diabetic retinopathy, micro-albuminuria and had worse survival compared to persons who were carriers of the most frequent alleles