Trial record 9 of 15 for:    "Diabetic Ketoacidosis"

Ketosis Prone Diabetes in African-Americans

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dawn Smiley MD, Emory University
ClinicalTrials.gov Identifier:
NCT00426413
First received: January 22, 2007
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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 Intervention
Ketosis Prone Diabetes
Diabetic Ketoacidosis
Severe Hyperglycemia
Drug: pioglitazone

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Ketosis Prone Diabetes Mellitus in African-Americans: Insulin Signaling, Proteomics, and Outcomes

Resource links provided by NLM:


Further study details as provided by Emory University:

Biospecimen Retention:   Samples With DNA

The study has IRB approval for blood sample collection for future DNA analyses and HLA typing.


Estimated Enrollment: 44
Study Start Date: May 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
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)
2
obese nondiabetic subjects, age 19-65.
3
Any subjects with recurrent DKA. Recurrent DKA is defined as more than one admission to Grady Memorial Hospital.

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00426413

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

No publications provided

Responsible Party: Dawn Smiley MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00426413     History of Changes
Other Study ID Numbers: IRB00024857, GCRC 1703, 897-2003
Study First Received: January 22, 2007
Last Updated: November 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
ketosis-prone diabetes
diabetic ketoacidosis
obesity
insulin dependence
mechanisms

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

ClinicalTrials.gov processed this record on September 15, 2014