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.