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Ketosis Prone Diabetes in African-Americans

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ClinicalTrials.gov Identifier: NCT00426413
Recruitment Status : Completed
First Posted : January 24, 2007
Last Update Posted : November 13, 2013
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment
Ketosis Prone Diabetes Diabetic Ketoacidosis Severe Hyperglycemia Drug: pioglitazone

Detailed 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.

Study Design

Study Type : Observational
Estimated Enrollment : 44 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Ketosis Prone Diabetes Mellitus in African-Americans: Insulin Signaling, Proteomics, and Outcomes
Study Start Date : May 2007
Primary Completion Date : August 2010
Study Completion Date : August 2010

Groups and Cohorts

Group/Cohort Intervention/treatment
Obese AA subjects with DKA or severe hyperglycemia
Drug: pioglitazone
Obese AA subjects with DKA or severe hyperglycemia that are able to discontinue insulin at 12 weeks or less will be randomized (blinded fashion) to receive either placebo or pioglitazone qd. The subjects will be followed while in the study arm and beta-cell function will be assessed using OGTT at set intervals.
Other Name: Actos (pioglitazone)
obese nondiabetic subjects, age 19-65.
Any subjects with recurrent DKA. Recurrent DKA is defined as more than one admission to Grady Memorial Hospital.

Outcome Measures

Biospecimen Retention:   Samples With DNA
The study has IRB approval for blood sample collection for future DNA analyses and HLA typing.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
36 Obese AA subjects with DKA or severe hyperglycemia and 8 obese nondiabetic subjects, age 19-65.

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00426413

United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
Principal Investigator: Dawn D Smiley, MD Emory University
More Information

Responsible Party: Dawn Smiley MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00426413     History of Changes
Other Study ID Numbers: IRB00024857
GCRC 1703 ( Other Identifier: Other )
897-2003 ( Other Identifier: Other )
First Posted: January 24, 2007    Key Record Dates
Last Update Posted: November 13, 2013
Last Verified: November 2013

Keywords provided by Dawn Smiley MD, Emory University:
ketosis-prone diabetes
diabetic ketoacidosis
insulin dependence

Additional relevant MeSH terms:
Diabetic Ketoacidosis
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acid-Base Imbalance
Diabetes Complications
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs