Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises

This study has been completed.
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT00753142
First received: September 12, 2008
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

Obesity is common in African-American patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA).1 Despite the presentation with severe symptoms of insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most obese AA patients with DKA have type 2 diabetes. In such patients, our previous studies reveal: a) at presentation, obese AA patients with DKA have markedly de-creased pancreatic insulin secretion, lower than in obese non-DKA patients admitted with comparable hyperglycemia, but significantly greater than in lean patients with DKA;2 b) aggressive diabetic management results in significant improvement in b-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of follow-up.2, 3 Based on these observations we conclude that similar to obese patients with hyperglycemia, most obese AA with DKA have type 2 diabetes, and that although defects in both insulin secretion and insulin action are present, transient b-cell failure is the primary defect in the development of ketoacidosis.


Condition Intervention
Hyperglycemia
Drug: Intralipid 20%
Drug: Glucose infusion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • First Phase Insulin Release (FPIR) [ Time Frame: at the end of 20 hours ] [ Designated as safety issue: No ]
    Calculated as the sum of the insulin levels at 2, 3, 4, and 5 min after infusion


Secondary Outcome Measures:
  • To Determine if Hyperglycemia-induced Reduced Insulin Secretion is the Result of Beta-cell Exhaustion or Beta-cell Desensitization. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: March 2004
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Subjects with ketosis-prone diabetes
Obese African-Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA)
Drug: Intralipid 20%
48hr infusion with intralipid at 40ml/hr
Drug: Glucose infusion
Glucose infusion for 20 hours at 200 mg/m2/min
Active Comparator: Subjects with ketosis-resistant diabetes
Obese African-American with type 2 diabetes with hyperglycemia but without ketosis
Drug: Intralipid 20%
48hr infusion with intralipid at 40ml/hr
Drug: Glucose infusion
Glucose infusion for 20 hours at 200 mg/m2/min
Active Comparator: Control
Obese African-American nondiabetic subjects
Drug: Glucose infusion
Glucose infusion for 20 hours at 200 mg/m2/min

Detailed Description:

Obese AA patients with a history of DKA who later experience near-normoglycemia remission represent an ideal population in which to define the sequence of events that lead to b-cell dysfunction in type 2 diabetes. We hypothesize that obese AA with DKA will prove particularly susceptible to b-cells dysfunction due to sustained elevations of plasma glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Obese African American subjects (BMI equal or greater than 30)
  2. age 18-65,
  3. patients with a history of diabetic ketoacidosis as defined by the ADA criteria
  4. patients admitted with hyperglycemia but without ketoacidosis (BG greater than 400ml/dl without evidence of ketosis/ketones
  5. obese nondiabetic controls (BMI >30; ruled out for diabetes with a 75g oral glucose tolerance test)

Exclusion Criteria:

  1. patients with positive autoimmune markers [islet cell (ICA) or Glutamic acid decarboxylase (GAD) autoantibodies];
  2. 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;
  3. patients with recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism;
  4. patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies;
  5. patients with fasting hyperglycemia (blood glucose > 120 mg/dl) after discontinuation of insulin therapy, and 6) pregnancy.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00753142

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
American Diabetes Association
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University
  More Information

Publications:
Responsible Party: Guillermo Umpierrez, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00753142     History of Changes
Other Study ID Numbers: 898-2003
Study First Received: September 12, 2008
Results First Received: July 7, 2014
Last Updated: July 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Hyperglycemia

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 19, 2014