Epigenetic Contribution to the Pathogenesis of Diabetic Nephropathy in Qatari Population

The main objective is to study the epigenetic contribution to the pathophysiology of diabetic nephropathy in Qatari population.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes

Detailed Description

Diabetic nephropathy (DN) is a common vascular complication of Type 2 diabetes (T2D) that is associated with increased mortality and poor quality of life.In industrialized countries, DN ranges first among other etiologies of end-stage renal disease (ESRD).Diabetes in Qatar is a serious health issue for the Qatari population since approximately 1/5 of the population has T2D, which is 2-3 times higher than the world average. As observed in other Gulf cooperation council (GCC) countries, obesity and sedentary lifestyle are cornerstones in the development of T2D. Additionally, consanguineous marriages in Qatar contribute to this high prevalence. As a consequence, DN has an enormous burden in terms of management, treatment and especially in renal replacement therapy (RRT) in ESRD in Qatari Population.DN is a glomerular disease defined by increased urinary albumin excretion (UAE), hypertension and decline in the glomerular filtration rate (GFR), all induced by chronic hyperglycemia. However, there are other contributing factors such as genetic predisposition, systemic and intra-renal hemodynamic disturbances, all leading to glomerulosclerosis. All of the known pathways do not explain the complex pathophysiology behind DN. Even different variants of genes described in major GWAS studies have little impact in terms of risk prevention or prognosis of DN. Over the last decade, epigenetics have initiated a new era in Genetic Medicine capable of giving a different approach to human disease.

• Study Type: Observational
• Enrollment (Actual): 158

Contacts and Locations

Study Locations

• Qatar
  • Doha, Qatar
    • Hamad Medical Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from Hamad Medical Corporation.

Description

Inclusion Criteria:

• Males and females, at least 18 years old
• Provide informed consent
• Willingness to participate in the study
• In patients with diabetes, no concomitant diseases except for micro and macrovascular complications of diabetes (nephropathy, retinopathy, peripheral arterial disease, coronary artery disease, neuropathy) or symptoms of the metabolic syndrome ( hypertension, dyslipidemia and obesity)
• Not taking any chronic medications (except of the diabetes and the cardiovascular related drugs)
• Consent to having peripheral blood and urine collection for DNA extraction and micro-RNAs as well as routine laboratory evaluation, including general hematologic studies, general biochemical analyses.

Exclusion Criteria:

• Type I diabetes or other form of diabetes (MODY, secondary diabetes)
• Unable to meet the inclusion criteria
• Pregnancy
• Active infection or acute illness of any kind
• Chronic inflammation (auto-immune diseases) or infections (HIV, chronic viral hepatitis, chronic urinary tract infections …)
• Evidence of malignancy within the past 5 years
• Chronic hematological disorders known to affect glycated hemoglobin results such as hemoglobinopathies and pathologies with high red-cell turnover

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Group I: T2D nephropathy; Individuals with type 2 diabetes and nephropathy
Group II: T2D and no nephropathy; Individuals with type 2 diabetes and no nephropathy
Group III: Control, non-diabetic; Non-diabetic individuals with normal kidney function
Group IV: Controls, non-diabetic; Non-diabetic individuals with hypertensive nephropathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA methylation	Assess DNA methylation in monocytes	1 hr

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Micro-RNAs	Assess urinary micro-RNAs	1 hr

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Hamad Medical Corporation; Weill Cornell Medical College in Qatar
• Investigators: Principal Investigator: Charbel Abi Khalil, MD, Weill Cornell Medical College in Qatar

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2014
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: December 9, 2014
• First Submitted That Met QC Criteria: December 9, 2014
• First Posted (Estimate): December 15, 2014

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies
• Other Study ID Numbers: 14-00043 [JIRB]

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED