- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00426413
Ketosis Prone Diabetes in African-Americans
November 12, 2013 updated by: Dawn Smiley MD, Emory University
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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Observational
Enrollment (Anticipated)
44
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30303
- Grady Memorial Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
17 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
36 Obese AA subjects with DKA or severe hyperglycemia and 8 obese nondiabetic subjects, age 19-65.
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
1
Obese AA subjects with DKA or severe hyperglycemia
|
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 Names:
|
2
obese nondiabetic subjects, age 19-65.
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|
3
Any subjects with recurrent DKA.
Recurrent DKA is defined as more than one admission to Grady Memorial Hospital.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Dawn D Smiley, MD, Emory University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2007
Primary Completion (Actual)
August 1, 2010
Study Completion (Actual)
August 1, 2010
Study Registration Dates
First Submitted
January 22, 2007
First Submitted That Met QC Criteria
January 23, 2007
First Posted (Estimate)
January 24, 2007
Study Record Updates
Last Update Posted (Estimate)
November 13, 2013
Last Update Submitted That Met QC Criteria
November 12, 2013
Last Verified
November 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Complications
- Acid-Base Imbalance
- Acidosis
- Hyperglycemia
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Ketosis
- Diabetic Ketoacidosis
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Pioglitazone
Other Study ID Numbers
- IRB00024857
- GCRC 1703 (Other Identifier: Other)
- 897-2003 (Other Identifier: Other)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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