| The purpose of this dissertation was to evaluate novel markers of glycemia and insulin resistance in conjunction with incident type 2 diabetes and carbohydrate dietary influences. Nontraditional markers of glucose homeostasis such as fructosamine, glycated albumin, 1,5-anhydroglucitol, and lactate are believed to have utility in quantifying concurrent hyperglycemic or insulin resistant states, but little is known regarding how these markers relate to traditional markers of glycemia as well as how they may relate to the risk of developing type 2 diabetes. Furthermore, the effects of dietary carbohydrates on these markers are unknown.;The first aim of this dissertation examines the association between fructosamine, glycated albumin, and 1,5-anhydroglucitol with traditional markers of glycose homeostasis, HbA1c and fasting glucose measurements. In this cross-sectional analysis of the Atherosclerosis Risk in Communities (ARIC) Study, we conclude that fructosamine and glycated albumin may be useful adjuncts to HbA1c and fasting glucose in the measurement of glycemia, while 1,5-anhydroglucitol has greater utility in the hyperglycemic range.;The second aim of this dissertation examined the prospective association between fructosamine, glycated albumin, 1,5-anhydroglucitol and incident type 2 diabetes in participants of ARIC, who had no history of diagnosed diabetes. We found that the upper quartiles of fructosamine and glycated albumin were significantly associated with diabetes risk, HRs 3.99 (95% CI: 1.93, 8.28) and 5.22 (95% CI: 2.49, 10.94), respectively. Meanwhile, the fourth quartile of 1,5AG was associated with a significantly lower diabetes risk, HR 0.27 (95% CI: 0.14, 0.55). These associations remained significant even after adjustment for hemoglobin A1c (A1c) or fasting glucose.;The third aim of this dissertation examined the longitudinal association of plasma lactate with incident type 2 diabetes in a case-cohort study of ARIC. We found that lactate was not only associated with diabetes risk factors at baseline, but was also associated with diabetes risk after a median of 9 years of follow-up. Further, after adjustment for demographic factors, medical history, physical activity, adiposity, and serum lipids, the hazard ratio in the highest quartile was 2.05 times the hazard in the lowest quartile (95% CI: 1.28, 3.28). This association was no longer significant when fasting glucose and insulin were included in models, however.;The fourth aim determined the association between plasma lactate and incident diabetes in adult participants of ARIC without a diagnosis of diabetes. Even after adjustment for fasting glucose and insulin, the upper quartile of lactate was associated with 1.2 times the risk of diabetes (95% CI: 1.02, 1.41) compared with the lowest quartile. Furthermore, this association persisted among participants without signs of insulin resistance (P-trend <0.01).;The fifth aim evaluated the effects of the amount and type of dietary carbohydrates on fasting glucose, glycated albumin and fructosamine in the Effect of Amount and Type of Dietary Carbohydrates on Risk for Cardiovascular Heart Disease and Diabetes (OmniCarb) Trial. Compared with diets of high glycemic index, a low glycemic index diet was associated with a 2 mg/dL increase in fasting glucose in a low carbohydrate diet (P = 0.02). A low carbohydrate and high glycemic index diet was associated with a lower glycated albumin when compared to a high carbohydrate and high glycemic index diet (P = 0.03). Similarly, among low glycemic index diets, a low carbohydrate diet was associated with a lower fructosamine when compared to a high carbohydrate diet (P = 0.002).;Overall, this dissertation adds clinical context to non-traditional markers of glucose homeostasis, describing potential roles for the markers in relationship to diabetes risk, identification, and glycemia monitoring. Furthermore, this dissertation examines how the amount and type of carbohydrates may influence these markers as surrogates for diabetes risk. |
