Trial Outcomes & Findings for Contribution of Hyperinsulinemia vs. Hyperglycemia to Insulin Resistance in Type 1 Diabetes and Maturity Onset Diabetes of the Young, Type 2 (MODY2) (NCT NCT02971202)
NCT ID: NCT02971202
Last Updated: 2019-08-01
Results Overview
The primary outcome is the degree to which Rd (determined using isotopic glucose tracer techniques) during maximal insulin stimulation differs between cohorts.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
End of clamp study (the study will last 8 hours)
Results posted on
2019-08-01
Participant Flow
Participant milestones
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
12
|
10
|
11
|
|
Overall Study
Started Study
|
11
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
Reasons for withdrawal
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Overall Study
Pregnancy
|
1
|
0
|
0
|
|
Overall Study
screen fail after consent
|
1
|
0
|
1
|
Baseline Characteristics
Contribution of Hyperinsulinemia vs. Hyperglycemia to Insulin Resistance in Type 1 Diabetes and Maturity Onset Diabetes of the Young, Type 2 (MODY2)
Baseline characteristics by cohort
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
n=12 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
n=11 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
28 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
24 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
33 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
31 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=93 Participants
|
10 participants
n=4 Participants
|
11 participants
n=27 Participants
|
33 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: End of clamp study (the study will last 8 hours)The primary outcome is the degree to which Rd (determined using isotopic glucose tracer techniques) during maximal insulin stimulation differs between cohorts.
Outcome measures
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Whole-body Glucose Utilization (Rd)
|
8.5 mg/kg FFM/min
Interval 6.1 to 10.9
|
11.0 mg/kg FFM/min
Interval 9.1 to 13.0
|
12.1 mg/kg FFM/min
Interval 10.3 to 14.0
|
SECONDARY outcome
Timeframe: 4 1/2 hours into clamp studyGlucose production (Ra) will be determined using stable isotopic tracer techniques. The extent to which Ra is suppressed at the end of 4 1/2 hours (when glucose Ra by liver has been submaximally suppressed) compared to basal (ΔRa) is directly proportional to hepatic insulin sensitivity.
Outcome measures
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Hepatic Insulin Sensitivity
|
1.9 mg/kg FFM/min
Interval 1.5 to 2.2
|
2.1 mg/kg FFM/min
Interval 1.7 to 2.4
|
1.7 mg/kg FFM/min
Interval 1.4 to 2.0
|
SECONDARY outcome
Timeframe: 4 1/2 hours into clamp studyInsulin sensitivity at fat is directly proportional to insulin's ability to suppress lipolysis. Thus, we will determine the extent to which submaximal insulin stimulation (4 1/2 hours into the study) suppresses glycerol and non-esterified free fatty acids (NEFAs) compared to baseline. The extent to which these two metabolites are suppressed is directly proportional to insulin sensitivity in adipose tissue. Here the suppression of NEFA is taken as the secondary outcome parameter.
Outcome measures
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
n=10 Participants
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Adipose Tissue Insulin Sensitivity
|
122.4 μmol/L
Interval -54.36 to 299.1
|
382.3 μmol/L
Interval 244.4 to 520.3
|
392.7 μmol/L
Interval 274.4 to 511.1
|
Adverse Events
Hyperinsulinemic, Euglycemic Clamp: T1DM
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Hyperinsulinemic, Euglycemic Clamp:MODY2
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Hyperinsulinemic Euglycemic Clamp:Control
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Hyperinsulinemic, Euglycemic Clamp: T1DM
n=12 participants at risk
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 milliunit (mU)/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic, Euglycemic Clamp:MODY2
n=10 participants at risk
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
Hyperinsulinemic Euglycemic Clamp:Control
n=11 participants at risk
Participants will undergo an 8-hour hyperinsulinemic, euglycemic clamp to quantify insulin sensitivity at whole-body and tissue-specific levels. The following hormones will be infused in the study:
* insulin (12 mU/m\^2/min \[3x basal\] for 150 minutes, then 40 mU/m\^2/min \[10x basal\] for 180 minutes)
* glucagon (0.65 ng/kg/min \[1x basal\] for 330 minutes)
* somatostatin (60 ng/kg/min) These infusions will maintain a basal glucagon level and an increased insulin level in the blood that will be equal between all 3 cohorts.
A variable infusion of 20% dextrose will be used to maintain plasma glucose within the euglycemic range throughout the hyperinsulinemic portion of the clamp. 6,6-H2 glucose will be infused at a low rate (0.033-0.22 µmol/kg/min) to determine glucose flux during the study.
|
|---|---|---|---|
|
Nervous system disorders
Vasovagal Response
|
8.3%
1/12 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/10 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/11 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
Nervous system disorders
headache
|
16.7%
2/12 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
20.0%
2/10 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
9.1%
1/11 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
Gastrointestinal disorders
nausea and vomiting
|
8.3%
1/12 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
10.0%
1/10 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
9.1%
1/11 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
General disorders
IV site pain
|
0.00%
0/12 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
10.0%
1/10 • Number of events 1 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
18.2%
2/11 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
Surgical and medical procedures
Swelling at biopsy site
|
0.00%
0/12 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/10 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
18.2%
2/11 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
Surgical and medical procedures
Redness at biopsy site
|
0.00%
0/12 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/10 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
18.2%
2/11 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
|
Cardiac disorders
hypotension
|
16.7%
2/12 • Number of events 2 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/10 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
0.00%
0/11 • 1 week
per protocol, hyperglycemia and hypoglycemia are not considered adverse events unless serious
|
Additional Information
Justin M. Gregory MD MSCI
Vanderbilt University Medical Center
Phone: 615-875-9669
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place