- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00753142
Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
September 14, 2018 updated by: Guillermo Umpierrez, MD, Emory University
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30303
- Grady Memorial Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: 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.
|
Participants receive a 48-hour infusion with Intralipid at 40 milliliters per hour (mL/hr).
Participants receive a glucose infusion consisting of 10% dextrose infused intravenously at a rate of 200 mg/m^2/min for 20 hours.
|
ACTIVE_COMPARATOR: Participants with ketosis-resistant diabetes
Obese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion.
|
Participants receive a 48-hour infusion with Intralipid at 40 milliliters per hour (mL/hr).
Participants receive a glucose infusion consisting of 10% dextrose infused intravenously at a rate of 200 mg/m^2/min for 20 hours.
|
ACTIVE_COMPARATOR: Non-diabetic control group
Obese African Americans without diabetes receiving a 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
First-Phase Insulin Release (FPIR)
Time Frame: Hour 0, Hour 20
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Beta-cell Failure
Time Frame: Hour 20
|
Pancreatic beta-cells can adapt to insulin resistance during the early stages of diabetes but continuous exposure of beta-cells to prolonged hyperglycemia can cause irreversible damage due to glucotoxicity.
This study aimed to evaluate whether hyperglycemia-induced reduced beta-cell failure was the result of beta-cell exhaustion or beta-cell desensitization, however, no participants experienced beta-cell failure so this original analysis could not be performed.
|
Hour 20
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2004
Primary Completion (ACTUAL)
December 1, 2009
Study Completion (ACTUAL)
December 1, 2009
Study Registration Dates
First Submitted
September 12, 2008
First Submitted That Met QC Criteria
September 15, 2008
First Posted (ESTIMATE)
September 16, 2008
Study Record Updates
Last Update Posted (ACTUAL)
October 12, 2018
Last Update Submitted That Met QC Criteria
September 14, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 898-2003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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