Ketosis Prone Diabetes in African-Americans

• Status: Completed
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Over 50% of obese African-Americans (AA) presenting with newly diagnosed, severe hyperglycemia and/or unprovoked diabetic ketoacidosis (DKA) display clinical, metabolic, and immunogenetic features of type 2 diabetes. Prior studies indicate that these patients a) have markedly decreased insulin secretion and impaired insulin action at presentation, b) absent or low prevalence of beta-cell autoantibodies and c) are able to discontinue aggressive insulin therapy in ~70% of cases within 3 months of follow-up. These patients have been referred to as having ketosis-prone type 2 diabetes (KPDM). Most patients with KPDM, however, experience a hyperglycemic relapse within a year of insulin discontinuation. Consequently, patients with "KPDM" are an ideal model to follow throughout their clinical course. The specific aims of this proposal are to 1) identify clinical, metabolic, and immunogenetic markers that alone, or in combination, are predictive of short- and long-term near-normoglycemic remission and 2) determine whether pioglitazone or sitagliptin therapy will delay an insulin-deficient relapse once insulin is discontinued. The Principal Investigator hypothesizes that measures of beta-cell function at presentation, alone or in combination with measures of insulin sensitivity, will correlate with the ability of a patient to achieve and remain in near-normoglycemic remission. She also hypothesizes that intervention compared to placebo will preserve beta-cell function, improve insulin sensitivity, and prevent an insulin-deficient relapse. This prospective, cohort study with a RCT arm would better characterize the natural history of KPDM, facilitate the direction of long-term therapy, and likely decrease the recurrence of DKA which is associated with increased mortality and morbidity.

• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Emory University
• Treatments: Insulin; Pioglitazone

Criteria

Inclusion Criteria:

• 36 Obese AA subjects with DKA or severe hyperglycemia and 8 obese nondiabetic subjects, age 19-65. All studies will be performed in the GCRC at Grady Memorial Hospital.

• Subjects with a BMI ≥ 28 kg/m2 will be included.

• Diagnostic criteria for DKA will include:

• a plasma glucose > 250 mg/dl,

• a venous pH < 7.30,

• a serum bicarbonate < 18 mEq/l, and

• high serum ketones.

• Obese hyperglycemic patients will have:

• a blood glucose on admission > 400 mg/dl,

• a serum bicarbonate > 18 mEq/l, and

• negative ketones.

Exclusion Criteria:

• 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 endocrine disorders, such as hypercortisolism, acromegaly, or hyperthyroidism;

• Bleeding disorders, or abnormalities in coagulation studies;

• Pregnancy.