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

NCT00753142 | Completed Results DMC

• 1 other identifier: 898-2003
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• First-Phase Insulin Release (FPIR)

  An arginine stimulation test was used to evaluate beta-cell function and insulin secretion. Increased glucose in the blood causes insulin to be released, beginning with a spike in insulin in the first 10 minutes and plateauing 2 to 3 later. Diminished first-phase insulin release is an early indicator of beta-cell dysfunction. Two sequential arginine stimulation tests were performed, the first set before and the second after completion of the 20-hour dextrose infusion. The first-phase insulin release (FPIR) was calculated as the sum of the insulin levels at 2, 3, 4, and 5 minutes after the arginine infusion. FPIR is expected to rise after the dextrose (glucose) infusion and FPIR generally rises less in persons with impaired glucose tolerance.

  Hour 0, Hour 20

Secondary Outcomes (1)

• Number of Participants With Beta-cell Failure

  Hour 20

Study Arms (3)

Participants with ketosis-prone diabetes

ACTIVE COMPARATOR

Obese African Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA) receiving Intralipid 20% and a glucose infusion.

Drug: Intralipid 20%; Drug: Glucose infusion

Participants with ketosis-resistant diabetes

ACTIVE COMPARATOR

Obese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion.

Drug: Intralipid 20%; Drug: Glucose infusion

Non-diabetic control group

ACTIVE COMPARATOR

Obese African Americans without diabetes receiving a glucose infusion.

Drug: Glucose infusion

Interventions

Intralipid 20% DRUG

Participants receive a 48-hour infusion with Intralipid at 40 milliliters per hour (mL/hr).

Participants with ketosis-prone diabetes; Participants with ketosis-resistant diabetes

Glucose infusion DRUG

Participants receive a glucose infusion consisting of 10% dextrose infused intravenously at a rate of 200 mg/m\^2/min for 20 hours.

Non-diabetic control group; Participants with ketosis-prone diabetes; Participants with ketosis-resistant diabetes

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• American Diabetes Association: collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Related Publications (1)

• 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.

  PMID: 20067967 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

404-778-1665

Study Officials

• Guillermo Umpierrez, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2008
• First Posted: September 16, 2008
• Study Start: March 1, 2004
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: October 12, 2018
• Results First Posted: August 1, 2014

Record last verified: 2018-09

Locations

US (1)