The Relationship Between Advanced Glycation Endproducts and Diabetes

NCT ID: NCT02662010

Last Updated: 2021-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

157 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-03-31

Study Completion Date

2020-01-17

Brief Summary

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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

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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 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)

Conditions

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Diabetic Retinopathy Type 2 Diabetes Mellitus

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Eligibility Criteria

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Inclusion Criteria

* 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.


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

* 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.


* 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.
Minimum Eligible Age

60 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ram Nagaraj, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado School of Medicine

Locations

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Universtiy of Colorado

Aurora, Colorado, United States

Site Status

Countries

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United States

References

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Milne R, Brownstein S. Advanced glycation end products and diabetic retinopathy. Amino Acids. 2013 Jun;44(6):1397-407. doi: 10.1007/s00726-011-1071-3. Epub 2011 Sep 11.

Reference Type BACKGROUND
PMID: 21909978 (View on PubMed)

Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1-21. doi: 10.1210/rp.56.1.1.

Reference Type BACKGROUND
PMID: 11237208 (View on PubMed)

Yan SF, D'Agati V, Schmidt AM, Ramasamy R. Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging. Curr Mol Med. 2007 Dec;7(8):699-710.

Reference Type BACKGROUND
PMID: 18331228 (View on PubMed)

Nowotny K, Jung T, Hohn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015 Mar 16;5(1):194-222. doi: 10.3390/biom5010194.

Reference Type BACKGROUND
PMID: 25786107 (View on PubMed)

Monnier VM, Sell DR, Genuth S. Glycation products as markers and predictors of the progression of diabetic complications. Ann N Y Acad Sci. 2005 Jun;1043:567-81. doi: 10.1196/annals.1333.065.

Reference Type BACKGROUND
PMID: 16037280 (View on PubMed)

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010 Oct 29;107(9):1058-70. doi: 10.1161/CIRCRESAHA.110.223545.

Reference Type BACKGROUND
PMID: 21030723 (View on PubMed)

Smuda M, Henning C, Raghavan CT, Johar K, Vasavada AR, Nagaraj RH, Glomb MA. Comprehensive analysis of maillard protein modifications in human lenses: effect of age and cataract. Biochemistry. 2015 Apr 21;54(15):2500-7. doi: 10.1021/bi5013194. Epub 2015 Apr 7.

Reference Type BACKGROUND
PMID: 25849437 (View on PubMed)

Other Identifiers

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UL1TR001082

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15-2029

Identifier Type: -

Identifier Source: org_study_id

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