Ketosis Prone Diabetes Mellitus in African-Americans: Insulin Signaling, Proteomics, and Outcomes
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.
Description
More than half of obese African-Americans (AA) with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) display clinical, metabolic, and immunogenetic features of type 2 diabetes during follow-up. Prior studies by our group and other investigators indicate that, at presentation, these patients a) have markedly decreased insulin secretion and impaired insulin action, b) have low prevalence of positive B-cell autoantibodies, and c) respond to aggressive diabetic management with significant improvement in B-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy. Upon discontinuation of insulin, the period of near-normoglycemia remission (defined as the ability to discontinue insulin injections for ��� one week and remain in good metabolic control - fasting blood glucose ��� 120 mg/dl and A1c ��� 7%) may last for a few months to several years. These patients are referred to as having atypical diabetes, Flatbush diabetes, or ketosis-prone type 2 diabetes (KPDM). Patients with “KPDM” are therefore an ideal model to follow throughout their clinical course in order to correlate their response to treatment with the mechanism(s) and markers of short- and long-term remission and determine the optimal therapeutic approach in order to prevent future glycemic decompensation.
Status: Completed (N/A). Started on May 1st, 2007.
Enrollment: 44 subjects
Study Type: Observational
Study Design:
- Observational Model: Cohort
- Time Perspective: Prospective
Conditions:
Interventions:
- Drug: pioglitazone (Actos (pioglitazone))
Eligibility
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;
- Gender
Both
- Mininum Age
19 Years
- Maximum Age
65 Years
- Healthy Volunteers
Accepts Healthy Volunteers
Resources
Source: Emory University
Authority: United States: Institutional Review Board
Locations
-
Grady Memorial Hospital
Atlanta
Georgia
30303
United States
Officials
Dawn D Smiley, MD (Principal Investigator, Emory University)
Sponsors
Emory University (Lead Sponsor)
References
None.
Links
None.
- Date Verified
- March 1st, 2011
- First Received
- March 7th, 2011
- Last Changed
- March 7th, 2011
Information obtained from ClinicalTrials.gov on June 09, 2011. Link to the current ClinicalTrials.gov record.
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