Associations between IGF-I, IGFBP-1, IGFBP-3 and Ghrelin with Diabetes and Diabetic Retinopathy in the Cardiovascular Health Study: A Cohort of Adults Aged ≥ 65 Years
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Diabetes disproportionately affects those ≥ 65 years and is associated with major morbidity and mortality. IGF proteins and ghrelin have been implicated in the development of diabetes and diabetic retinopathy. Despite biological implication of IGF proteins in disease processes, there are still gaps in the literature.;Using data from the Cardiovascular Health Study, a cohort of adults ≥ 65 years, this thesis assessed: a) associations between IGF proteins and incident diabetes, b) changes in IGF proteins with worsening glycemia, c) associations between IGF proteins and diabetic retinopathy and d) genetic and non-genetic correlates of IGF proteins. There were several findings in this thesis:;First: Associations with incident diabetes varied by sex. In women, higher IGFBP-3 and lower fasting ghrelin were significantly associated with incident diabetes. In men, for those with high insulin levels, fasting IGFBP-1 and 2-hour IGFBP-1 were directly associated with incident diabetes. For those with low insulin levels, fasting IGFBP-1, but not 2-hour IGFBP-1, was inversely associated with incident diabetes.;Second: The greatest 9-year percent changes in IGF-I, IGFBP-1 and IGFBP-3 occurred in those who had diabetes at baseline, the smallest in individuals who remained normoglycemic at follow-up and intermediate changes in those who were normoglycemic at baseline but developed prediabetes at follow-up.;Third: Diabetic retinopathy was observed in those free of diabetes (7%), although a third of participants with retinopathy had diabetes. High IGF-I, high IGFBP-3, and maintenance of high IGFBP-3 levels over a 3-year were significantly associated with lower odds of retinopathy.;Fourth: The R2 values were larger for women than for men; for fasting and post-OGTT levels of IGF and ghrelin levels, R2 ranged from 16% to 48% in women and 8 to 47% in men. Nutrition variables and genetic risk scores contributed little to variability in IGF protein levels.;Collectively, we have shown that men and women had marked differences in correlates of IGF and ghrelin levels and on association with incident diabetes. IGF protein may serve as diabetes risk biomarkers in older adult populations, may be used to track individuals with worsening glycemic status and possibly identify persons with diabetic retinopathy.