The Relationship Between Advanced Glycation Endproducts and Diabetes
Condition: Diabetic Retinopathy; Type 2 Diabetes Mellitus
MeSH terms: Retinal Diseases; Diabetic Retinopathy; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      The overall purpose of this COMIRB application is to perform a cross-sectional pilot study to
      aid in the design of a prospective epidemiologic study for an NIH grant application. The long
      term goal of this research is to determine if AGEs are predictors of glycemic control and the
      development of diabetic retinopathy in patients with T2DM. Understanding these relationships
      could lead to a prospective prediction of the onset/worsening of diabetic retinopathy in T2DM
      patients and in pre-diabetic individuals.
    

Detailed description: 
      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)
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The Investigators propose recruiting 80 subjects (40 with no diabetes, 20 with diabetes and
        no diabetic retinopathy and 20 with diabetes and diabetic retinopathy).

        Within the 40 control patients without a clinical diagnosis of T2DM, 20 will have an
        abnormal HbA1C at the time of surgery. It is important to enroll the patients with an
        abnormal HbA1C in order to see if there are early manifestations of an abnormal glucose
        level as detected by AGEs in the anterior lens capsule.
      
Biospecimen description: 
      Buffy Coat
    
Keywords: AGEs; glycemic control; T2DM