Glucose Metabolism in Sickle Cell Disease

N/AActive Not RecruitingNCT02922296

University of Illinois at Chicago75 enrolled

Overview

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.

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

Conditions

Sickle Cell Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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)

Time frame: through study completion, approximately one year after subject participation

Secondary Outcomes

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.