Clinical trial NCT00753142: Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
Official title: Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: Hyperglycemia
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2008-09-16
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obesity is common in African American (AA) patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA). 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, previous studies reveal that: a) at presentation, obese AA patients with DKA have markedly decreased pancreatic insulin secretion, lower than in obese non-DKA patients admitted with comparable hyperglycemia, but significantly greater than in lean patients with DKA; b) aggressive diabetic management results in significant improvement in beta-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of follow-up. Based on these observations the researchers 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.

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. The researchers hypothesize that obese AA with DKA will prove particularly susceptible to beta-cells dysfunction due to sustained elevations of plasma glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity). This study will test beta-cell response by administering a glucose infusion to diabetic African Americans with a history of DKA, diabetic African Americans without a history of DKA, and non-diabetic African Americans.

Eligibility criteria: Inclusion Criteria:

* Obese African American subjects (body mass index (BMI) equal or greater than 30)
* Age 18-65
* Patients with a history of diabetic ketoacidosis as defined by the American Diabetes Association (ADA) criteria
* Patients admitted with hyperglycemia but without ketoacidosis (blood glucose greater than 400ml/dl without evidence of ketosis/ketones
* Obese nondiabetic controls (BMI \>30; ruled out for diabetes with a 75g oral glucose tolerance test)

Exclusion Criteria:

* Patients with positive autoimmune markers (islet cell or glutamic acid decarboxylase (GAD) autoantibodies)
* 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 or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism
* Patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies
* Patients with fasting hyperglycemia (blood glucose \> 120 mg/dl) after discontinuation of insulin therapy
* Pregnancy

Primary outcomes:
measure: First-Phase Insulin Release (FPIR)
timeFrame: Hour 0, Hour 20
Secondary outcomes:
measure: Number of Participants With Beta-cell Failure
timeFrame: Hour 20
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gosmanov AR, Smiley D, Robalino G, Siqueira JM, Peng L, Kitabchi AE, Umpierrez GE. Effects of intravenous glucose load on insulin secretion in patients with ketosis-prone diabetes during near-normoglycemia remission. Diabetes Care. 2010 Apr;33(4):854-60. doi: 10.2337/dc09-1687. Epub 2010 Jan 12.