An interventional study of Hyperinsulinemic, euglycemic and hypoglycemic clamp in Diabetes Mellitus, Type 1, sponsored by University of Virginia. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-09-08.
Sponsored by University of Virginia · Not applicable and Interventional
The researchers plan to test the following hypothesis:
A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body:
The researchers plan to investigate the relationships between hypoglycemia, insulin transport, and counter-regulation. This study will ultimately lead to a better understanding of risk for recurrent hypoglycemia.
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 41 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
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Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.
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Exclusion Criteria:
One month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Procedure: Hyperinsulinemic, euglycemic and hypoglycemic clamp
At 21:30h, an overnight insulin infusion was titrated to control the subjects' BG overnight between 100 and 150mg/dL by blood sampling for plasma glucose via a YSI analyzer every 30min and adjusting the rate of insulin infusion as needed. At the beginning of the clamp, the overnight insulin was replaced by an insulin infusion via a Harvard pump given as a 20mU/kg priming over a 10-min period, followed by a constant rate delivery of 1mU/kg/min until the end of the clamp. Blood was sampled for plasma glucose, and glucose was clamped at basal levels for the euglycemic control period of 150min via a variable-rate infusion of 20% dextrose. Then the glucose concentration was lowered at a rate of 1mg/dL/min to a minimum of 50mg/dL, where it was held constant for 30min. Finally, the glucose concentration was increased at a rate of 1mg/dL/min to 90mg/dL, where it was held for an additional 30min. Blood was sampled for epinephrine during euglycemia, hypoglycemia, and recovery.
Maximum Epinephrine Response (LBGI Groups)
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI \< 2.5; Moderate Risk, 2.5 \< LBGI \< 5; and High Risk, LBGI \> 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.
Time frame: 285 min (time of clamp)
Maximum Epinephrine Response (ADRR Groups)
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia. Low Risk, ADRR \< 20; Moderate Risk, 20 \< ADRR \< 40; and High Risk,ADRR \> 40.
Time frame: 285 min (time of clamp)
Recruitment period: 2/2006-5/2009. Recruitment included outpatients at UVA clinics, former research subjects, and local advertising. All subjects ≥18 years of age and had type 1 diabetes defined by American Diabetes Association criteria or judgment of the study endocrinologist after review of the clinical history.
| Milestone | Adults With T1DM From Subjects |
|---|---|
| Started | 41 |
| Completed | 34 |
| Not completed | 7 |
| Withdrew: Physician decision | 4 |
| Withdrew: Withdrawal by subject | 3 |
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI \< 2.5; Moderate Risk, 2.5 \< LBGI \< 5; and High Risk, LBGI \> 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.
| pg/ml | Adults With T1DM From Subjects |
|---|---|
| LBGI < 2.5 | 495 ± 60 |
| LBGI >= 2.5 | 217 ± 40 |
Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia. Low Risk, ADRR \< 20; Moderate Risk, 20 \< ADRR \< 40; and High Risk,ADRR \> 40.
| pg/ml | Adults With T1DM From Subjects |
|---|---|
| ADRR < 40 | 417 ± 45 |
| ADRR >= 40 | 167 ± 45 |
Collected over 3 years. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Adults With T1DM From Subjects | — | 3/34 (8.8%) | 8/34 (23.5%) |
| Event | Adults With T1DM From Subjects |
|---|---|
| Orthostatic HypotensionVascular disorders | 2/34 |
| Vasovagal HypotensionVascular disorders | 1/34 |
| Event | Adults With T1DM From Subjects |
|---|---|
| HyperglycemiaEndocrine disorders | 2/34 |
| HeadacheNervous system disorders | 2/34 |
| DizzinessNervous system disorders | 1/34 |
| Lower Back PainGeneral disorders | 1/34 |
| Abdomen ecchymosis near Guardian siteSkin and subcutaneous tissue disorders | 1/34 |
| Chest PainGeneral disorders | 1/34 |
| Age, Categorical(Participants) | Adults With T1DM From Subjects |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 34 |
| >=65 years | 0 |
| Age, Continuous(years) | Adults With T1DM From Subjects |
|---|---|
| Mean | 37 ± 2.1 |
| Sex: Female, Male(Participants) | Adults With T1DM From Subjects |
|---|---|
| Female | 14 |
| Male | 20 |
| Region of Enrollment(participants) | Adults With T1DM From Subjects |
|---|---|
| United States | 34 |
| Glycosylated hembglobin (HbA1c)(percent) | Adults With T1DM From Subjects |
|---|---|
| Mean | 7.6 ± 0.21 |
This study is completed, as verified in Aug 2014. You cannot join it, but the record below documents what was studied.
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