The Relationship Between Advanced Glycation Endproducts and Diabetes

June 25, 2021 updated by: University of Colorado, Denver

The Relationship of Advanced Glycation Endproducts in the Anterior Lens Capsule to Glycemic Status and Diabetic Retinopathy: A Cross Sectional Study of Patients With and Without Type 2 Diabetes Mellitus Undergoing Cataract Surgery

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.

Study Overview

Status

Completed

Conditions

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)

Study Type

Observational

Enrollment (Actual)

157

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Universtiy of Colorado

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

Inclusion criteria (cases):

  • T2DM as documented by the referring physician, an HbA1C level of greater than 5.7 mmol/mol, or on T2DM medications beyond Metformin.
  • 50% of the cases will have diabetic retinopathy as documented by the attending ophthalmologist and 50% will have no retinopathy.
  • Age 60-80 years old.

Inclusion criteria (controls):

  1. Normal HbA1C

    • No diabetes as documented by the referring physician, a HbA1C level of less than or equal to 5.7 mmol/mol, or not taking medications for T2DM with the exception of Metformin.
    • Age 60-80 years old.

  2. Abnormal HbA1C

    • No diabetes as documented by the referring physician, a HbA1C level between 5.7 and 6.5 mmol/mol, and not taking medications for T2DM with the exception of Metformin.
    • Age 60-80 years old.

Exclusion criteria (cases):

  • Type 1 diabetes as documented by the referring physician.
  • <60 years old or >80 years old.
  • If the patient has bilateral cataract surgery, the second surgery will be excluded
  • Patients who have active cancer, being treated (receiving Chemotherapy or Radiation therapy) or disseminated, recent CVD event, MI or CVA within 6 months, and disease related weight loss of more than 10% in the past 3-6 months.

Exclusion criteria (controls):

  • Type 1 or T2DM as documented by the referring physician.
  • <60 years old or >80 years old.
  • No treatment with Metformin or modifiers for risk of T1DM
  • If the patient has bilateral cataract surgery, the second surgery will be excluded
  • Patients who have active cancer, being treated (receiving Chemotherapy or Radiation therapy) or disseminated, recent CVD event, MI or CVA within 6 months, and disease related weight loss of more than 10% in the past 3-6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in Advanced Glycation Endproducts (AGE) Levels
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in HbA1C Levels
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Investigators

  • Principal Investigator: Ram Nagaraj, PhD, University of Colorado School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

January 17, 2020

Study Completion (Actual)

January 17, 2020

Study Registration Dates

First Submitted

January 20, 2016

First Submitted That Met QC Criteria

January 22, 2016

First Posted (Estimate)

January 25, 2016

Study Record Updates

Last Update Posted (Actual)

June 28, 2021

Last Update Submitted That Met QC Criteria

June 25, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-2029
  • UL1TR001082 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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