Glucose Metabolism in Sickle Cell Disease

The purpose of the study is to better understand how the body handles sugars glucose and fats, such as cholesterol and triglycerides in sickle cell disease, and what puts certain persons at risk to develop diabetes. This understanding may help us to find new treatments to control blood sugar and prevent diabetes in people with and without sickle cell disease (SCD).

In this research, DNA and RNA will be isolated from blood cells. DNA will be used to find genes that cause or protect from diabetes, high cholesterol and high triglyceride, and RNA will be used for studies designed to find out how genes are doing their job of eventually producing proteins.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Sickle Cell Disease

Detailed Description

Sickle cell disease (SCD) is due to homozygosity for a Glu6Val mutation in HBB (sickle cell anemia; hemoglobin SS) or to compound heterozygous forms like hemoglobin SC disease and hemoglobin S-β thalassemia. Past studies suggested a low prevalence of diabetes in patients with SCD.10 Improvements in treatment and care have increased the life span of patients. This, along with the wide availability of high calorie diets and increasing adiposity in SCD raises that possibility that the prevalence of diabetes is increasing in SCD. Our study is designed to characterize the changes in metabolism that occur in sickle cell disease and to identify clinical, genetic and genomic risk factors for the development of diabetes. Our hypothesis is that non-overweight subjects with SCD have relative protection from diabetes and metabolic syndrome, but that those individuals who do become overweight have a dramatic increase in the rates of diabetes and metabolic syndrome. Lean SCD subjects will not have simply a neutral, but an overtly anti-diabetic phenotype (e.g. better glucose tolerance and lower metabolic syndrome markers). The two main study aims are as follows; Aim 1. Define the metabolic status of adult SCD subjects according to normal or increased BMI.

Aim 2. Determine genetic and genomic predictors of overweight, metabolic syndrome and diabetes in SCD subjects.

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: Victor Gordeuk, MD; Phone Number: 312-996-5680; Email: vgordeuk@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois at Chicago
      • Contact: Victor Gordeuk, MD; Phone Number: 312-996-5680; Email: vgordeuk@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult sickle cell disease subjects, with or without diabetes.

Description

Inclusion Criteria:

• Major sickling genotype (hemoglobin SS, Sbeta0-thalassemia, SOarab, SDpunjab)
• Age >35 years
• BMI <25 kg/m2 or >26 kg/m2
• Steady state, defined as >two weeks from a hospitalization for vaso-occlusive crisis, infection or surgery and not requiring immediate parenteral medication for pain control
• Fasting state (>8 hours since ingesting food or medication for diabetes)

Exclusion Criteria:

• Patients receiving insulin therapy
• Acute inflammatory or infectious illness or injury

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic status of adult SCD subjects	The investigator will use the ATP III guidelines for definition of metabolic syndrome. A combination of any three of the following criteria will lead to the designation of metabolic syndrome: waist circumference >102 cm (men) or >88 cm (women); triglycerides ≥150 mg/dL; HDL cholesterol <40 mg/dL (men) or <50 mg/dL (women); blood pressure ≥130/≥85 mg/dL (or recorded diagnosis of hypertension and use of antihypertensives); fasting glucose ≥110 mg/dL (or diagnosis of diabetes and use of anti-diabetic medications)	through study completion, approximately one year after subject participation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic and genomic predictors in SCD subjects	This will be accomplished by DNA linkage analysis and/or mutation analysis. In addition RNA will be isolated from from PBMCs and fractions of platelets, granulocytes and reticulocytes. The investigators will analyze the expression of transcripts to determine if alterations can explain the clinical observations.	through study completion, approximately one year after subject participation

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Victor Gordeuk, MD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 31, 2016
• First Submitted That Met QC Criteria: September 29, 2016
• First Posted (Estimated): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 2015-0366

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO