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

NCT ID: NCT00753142

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2009-12-31

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with ketosis-prone diabetes

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

Group Type: ACTIVE_COMPARATOR

Intralipid 20%

Intervention Type: DRUG

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

Glucose infusion

Intervention Type: DRUG

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

Participants with ketosis-resistant diabetes

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

Group Type: ACTIVE_COMPARATOR

Intralipid 20%

Intervention Type: DRUG

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

Glucose infusion

Intervention Type: 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

Obese African Americans without diabetes receiving a glucose infusion.

Group Type: ACTIVE_COMPARATOR

Glucose infusion

Intervention Type: DRUG

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

Interventions

Intralipid 20%

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

Intervention Type: DRUG

Glucose infusion

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Guillermo Umpierrez, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo Umpierrez, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 20067967 (View on PubMed)

Other Identifiers

898-2003

Identifier Type: -

Identifier Source: org_study_id