The Relationship Between Advanced Glycation Endproducts and Diabetes

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Below are the specific aims and research hypotheses for the pilot study: Specific Aim 1: To successfully recruit 80 subjects (40 with no diabetes, 20 with diabetes and no diabetic retinopathy and 20 with diabetes and diabetic retinopathy) and obtain adequate samples (blood and lens capsule) for furt...

Below are the specific aims and research hypotheses for the pilot study: Specific Aim 1: To successfully recruit 80 subjects (40 with no diabetes, 20 with diabetes and no diabetic retinopathy and 20 with diabetes and diabetic retinopathy) and obtain adequate samples (blood and lens capsule) for further testing. Hypothesis 1: Recruitment of subjects with and without diabetes and diabetic retinopathy is feasible within our clinic and the process for collecting, processing and storing samples is adequate to support the full study. Specific Aim 2: To measure anterior lens capsule AGEs and HbA1c levels in recruited patients. Hypothesis 2: Levels of AGEs and HbA1c will be quantifiable in collected samples. The pilot study aims are necessary to determine the feasibility of the full study, as well as to provide estimates of the (1) proportion of non-diabetic subjects with Abnormal HbA1c, (2) effect sizes and (3) variances for planning the full study. The planned specific aims and research hypotheses for the full study are as follows: Specific Aim 1: To determine whether anterior lens capsule AGEs differ in patients with and without a clinical diagnosis of T2DM. Hypothesis 1: Levels of AGEs will be higher in patients with a clinical diagnosis of T2DM compared with patients without a clinical diagnosis of diabetes. Specific Aim 2: To determine if levels of AGEs measured from the anterior lens capsule are correlated with levels of Hemoglobin A1c (HbA1c) in patients without T2DM. Hypothesis 2: Levels of HbA1c will positively correlate with levels of HbA1c in all patients. Specific Aim 3: To determine among patients with T2DM if levels of AGEs measured from the anterior lens capsule are higher in the group with diabetic retinopathy compared with the group with no diabetic retinopathy. Hypothesis 3: That among patients with T2DM: Levels of AGEs will be higher in the patients with diabetic retinopathy compared with the patients with no diabetic retinopathy. AGEs are elevated in patients with diabetes (1, 3) and are reported to have a role in diabetic complications. (4, 5) Hyperglycemia results in higher intracellular glucose levels and the formation of metabolites from many complex interactions which in turn increase the production of AGEs. AGEs are a source of reactive oxygen species (ROS) with results in oxidative stress to tissues.(4) As reported, oxidative stress plays an important role in the microvascular and cardiovascular pathologic processed described in T2DM. (6) Importantly, oxidative stress is causal in the development of b cell dysfunction and insulin resistance, the two hallmarks of T2DM. (4)

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