Trial Outcomes & Findings for Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises (NCT NCT00753142)

NCT ID: NCT00753142

Last Updated: 2018-10-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

28 participants

Primary outcome timeframe

Hour 0, Hour 20

Results posted on

2018-10-12

Participant Flow

Participant enrollment began in March 2004 and all study follow-up was completed in December 2009. The study was conducted at the Clinical Research Center at Grady Memorial Hospital in Atlanta, Georgia.

Participant milestones

Participant milestones
Measure
Ketosis-prone Diabetics
Obese African Americans with type 2 diabetes and a history of diabetic ketoacidosis (DKA) receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Ketosis-resistant Diabetics
Obese African Americans with type 2 diabetes with hyperglycemia without ketosis receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused 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 of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Overall Study
STARTED
8
7
13
Overall Study
COMPLETED
8
7
13
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ketosis-prone Diabetics
n=8 Participants
Obese African Americans with type 2 diabetes and a history of diabetic ketoacidosis (DKA) receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Ketosis-resistant Diabetics
n=7 Participants
Obese African Americans with type 2 diabetes with hyperglycemia without ketosis receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Non-diabetic Control Group
n=13 Participants
Obese African Americans without diabetes receiving a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Total
n=28 Participants
Total of all reporting groups
Age, Continuous
42.8 years
STANDARD_DEVIATION 10.6 • n=5 Participants
49.7 years
STANDARD_DEVIATION 8.1 • n=7 Participants
40 years
STANDARD_DEVIATION 9.3 • n=5 Participants
44 years
STANDARD_DEVIATION 9 • n=4 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
2 Participants
n=7 Participants
12 Participants
n=5 Participants
16 Participants
n=4 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
5 Participants
n=7 Participants
1 Participants
n=5 Participants
12 Participants
n=4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Black or African American
8 Participants
n=5 Participants
7 Participants
n=7 Participants
13 Participants
n=5 Participants
28 Participants
n=4 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Region of Enrollment
United States
8 Participants
n=5 Participants
7 Participants
n=7 Participants
13 Participants
n=5 Participants
28 Participants
n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Ketosis-prone Diabetics
n=8 Participants
Obese African Americans with type 2 diabetes and a history of diabetic ketoacidosis (DKA) receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Ketosis-resistant Diabetics
n=7 Participants
Obese African Americans with type 2 diabetes with hyperglycemia without ketosis receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Non-diabetic Control Group
n=13 Participants
Obese African Americans without diabetes receiving a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
First-Phase Insulin Release (FPIR)
Before glucose infusion
264 microunits/ml
Standard Deviation 80
339 microunits/ml
Standard Deviation 221
197 microunits/ml
Standard Deviation 33
First-Phase Insulin Release (FPIR)
After glucose infusion
359 microunits/ml
Standard Deviation 42
381 microunits/ml
Standard Deviation 147
299 microunits/ml
Standard Deviation 30

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Ketosis-prone Diabetics
n=8 Participants
Obese African Americans with type 2 diabetes and a history of diabetic ketoacidosis (DKA) receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Ketosis-resistant Diabetics
n=7 Participants
Obese African Americans with type 2 diabetes with hyperglycemia without ketosis receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Non-diabetic Control Group
n=13 Participants
Obese African Americans without diabetes receiving a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Number of Participants With Beta-cell Failure
0 Participants
0 Participants
0 Participants

Adverse Events

Ketosis-prone Diabetics

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Ketosis-resistant Diabetics

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Non-diabetic Control Group

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Ketosis-prone Diabetics
n=8 participants at risk
Obese African Americans with type 2 diabetes and a history of diabetic ketoacidosis (DKA) receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Ketosis-resistant Diabetics
n=7 participants at risk
Obese African Americans with type 2 diabetes with hyperglycemia without ketosis receiving a 48-hour infusion of Intralipid 20% at 40 mL/hour and a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Non-diabetic Control Group
n=13 participants at risk
Obese African Americans without diabetes receiving a glucose infusion of 10% dextrose infused at a rate of 200 mg/m\^2/min for 20 hours.
Endocrine disorders
hyperglycemia
12.5%
1/8
14.3%
1/7
0.00%
0/13

Additional Information

Guillermo Umpierrez

Emory University

Phone: 404-778-1665

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place