Trial Outcomes & Findings for Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus (NCT NCT00943787)

NCT ID: NCT00943787

Last Updated: 2014-09-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

41 participants

Primary outcome timeframe

285 min (time of clamp)

Results posted on

2014-09-08

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Adults With T1DM From Subjects
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Overall Study
STARTED
41
Overall Study
COMPLETED
34
Overall Study
NOT COMPLETED
7

Reasons for withdrawal

Reasons for withdrawal
Measure
Adults With T1DM From Subjects
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Overall Study
Physician Decision
4
Overall Study
Withdrawal by Subject
3

Baseline Characteristics

Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Adults With T1DM From Subjects
n=34 Participants
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
34 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Age, Continuous
37 years
STANDARD_DEVIATION 2.1 • n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
Region of Enrollment
United States
34 participants
n=5 Participants
Glycosylated hembglobin (HbA1c)
7.6 percent
STANDARD_DEVIATION 0.21 • n=5 Participants

PRIMARY outcome

Timeframe: 285 min (time of clamp)

Population: 3 participants did not have adequate epinephrine data.

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.

Outcome measures

Outcome measures
Measure
Adults With T1DM From Subjects
n=31 Participants
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Maximum Epinephrine Response (LBGI Groups)
LBGI < 2.5
495 pg/ml
Standard Deviation 60
Maximum Epinephrine Response (LBGI Groups)
LBGI >= 2.5
217 pg/ml
Standard Deviation 40

SECONDARY outcome

Timeframe: 285 min (time of clamp)

Population: 3 participants did not have enough epinephrine data

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.

Outcome measures

Outcome measures
Measure
Adults With T1DM From Subjects
n=31 Participants
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Maximum Epinephrine Response (ADRR Groups)
ADRR < 40
417 pg/ml
Standard Deviation 45
Maximum Epinephrine Response (ADRR Groups)
ADRR >= 40
167 pg/ml
Standard Deviation 45

Adverse Events

Adults With T1DM From Subjects

Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Adults With T1DM From Subjects
n=34 participants at risk
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Vascular disorders
Orthostatic Hypotension
5.9%
2/34 • Number of events 2 • 3 years
Vascular disorders
Vasovagal Hypotension
2.9%
1/34 • Number of events 2 • 3 years

Other adverse events

Other adverse events
Measure
Adults With T1DM From Subjects
n=34 participants at risk
Subjects with type 1 diabetes performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
Endocrine disorders
Hyperglycemia
5.9%
2/34 • Number of events 2 • 3 years
Nervous system disorders
Dizziness
2.9%
1/34 • Number of events 1 • 3 years
Nervous system disorders
Headache
5.9%
2/34 • Number of events 2 • 3 years
General disorders
Lower Back Pain
2.9%
1/34 • Number of events 1 • 3 years
Skin and subcutaneous tissue disorders
Abdomen ecchymosis near Guardian site
2.9%
1/34 • Number of events 1 • 3 years
General disorders
Chest Pain
2.9%
1/34 • Number of events 1 • 3 years

Additional Information

Mary Oliveri

University of Virginia

Phone: 434-982-0602

Results disclosure agreements

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