Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
Obesity is common in African American (AA) patients with newly diagnosed diabetes who present
 with diabetic ketoacidosis (DKA). Despite the presentation with severe symptoms of
 insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most
 obese AA patients with DKA have type 2 diabetes. In such patients, previous studies reveal
 that: a) at presentation, obese AA patients with DKA have markedly decreased pancreatic
 insulin secretion, lower than in obese non-DKA patients admitted with comparable
 hyperglycemia, but significantly greater than in lean patients with DKA; b) aggressive
 diabetic management results in significant improvement in beta-cell function and insulin
 sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of
 follow-up. Based on these observations the researchers conclude that similar to obese
 patients with hyperglycemia, most obese AA with DKA have type 2 diabetes, and that although
 defects in both insulin secretion and insulin action are present, transient b-cell failure is
 the primary defect in the development of ketoacidosis.
Obese AA patients with a history of DKA who later experience near-normoglycemia remission
 represent an ideal population in which to define the sequence of events that lead to b-cell
 dysfunction in type 2 diabetes. The researchers hypothesize that obese AA with DKA will prove
 particularly susceptible to beta-cells dysfunction due to sustained elevations of plasma
 glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity). This study will test
 beta-cell response by administering a glucose infusion to diabetic African Americans with a
 history of DKA, diabetic African Americans without a history of DKA, and non-diabetic African
 Americans.
Inclusion Criteria:

 -  Obese African American subjects (body mass index (BMI) equal or greater than 30)

 -  Age 18-65

 -  Patients with a history of diabetic ketoacidosis as defined by the American Diabetes
 Association (ADA) criteria

 -  Patients admitted with hyperglycemia but without ketoacidosis (blood glucose greater
 than 400ml/dl without evidence of ketosis/ketones

 -  Obese nondiabetic controls (BMI >30; ruled out for diabetes with a 75g oral glucose
 tolerance test)

 Exclusion Criteria:

 -  Patients with positive autoimmune markers (islet cell or glutamic acid decarboxylase
 (GAD) autoantibodies)

 -  Patients with significant medical or surgical illness, including but not limited to
 myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver
 failure, and infectious processes

 -  Patients with recognized or suspected endocrine disorders associated with increased
 insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism

 -  Patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation
 studies

 -  Patients with fasting hyperglycemia (blood glucose > 120 mg/dl) after discontinuation
 of insulin therapy

 -  Pregnancy