Trial Outcomes & Findings for Insulin Secretion in Diabetes Before and After Glycemic Control (NCT NCT00469833)

Results Overview

Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

180 minutes

Results posted on

2015-01-15

Participant Flow

Recruited from VAMC from 2010-2012

No subjects excluded

Participant milestones

Participant milestones
Measure	Uncontrolled Type 2 Diabetic Subjects Eligible subjects will have measures of insulin secretion measured using the OGTT/hyperglycemic clamp technique before and after 2 months of treatment to lower blood glucose.
Overall Study STARTED	17
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Uncontrolled Type 2 Diabetic Subjects Eligible subjects will have measures of insulin secretion measured using the OGTT/hyperglycemic clamp technique before and after 2 months of treatment to lower blood glucose.
Overall Study No IV access	2

Baseline Characteristics

Insulin Secretion in Diabetes Before and After Glycemic Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=17 Participants Within subjects comparison; before and after treatment. Beta-cell function measured with OGTT/hyperglycemic clamp
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants

PRIMARY outcome

Timeframe: 180 minutes

Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.

Outcome measures

Outcome measures
Measure	Oral Glucose n=15 Participants Oral glucose administered to uncontrolled type 2 diabetic subjects.	IV Glucose n=15 Participants IV glucose administered to uncontrolled type 2 diabetic subjects.
ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. Insulin secretion at baseline	0.67 pmol/min Standard Error 0.07	0.75 pmol/min Standard Error 0.10
ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. Insulin secretion at 8 weeks	1.11 pmol/min Standard Error 0.22	0.76 pmol/min Standard Error 0.11

PRIMARY outcome

Timeframe: 180 minutes

Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.

Outcome measures

Outcome measures
Measure	Oral Glucose n=15 Participants Oral glucose administered to uncontrolled type 2 diabetic subjects.	IV Glucose n=15 Participants IV glucose administered to uncontrolled type 2 diabetic subjects.
C-peptide Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. C-peptide at baseline	7.10 nmol/L Standard Error 0.92	5.63 nmol/L Standard Error 0.97
C-peptide Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. C-peptide at 8 weeks	10.89 nmol/L Standard Error 2.20	6.02 nmol/L Standard Error 0.88

PRIMARY outcome

Timeframe: 180 minutes

Subjects had glucose clamps for 270 minutes with serial sampling of blood for measurement of insulin and C-peptide. At 90 minutes into the clamp they consumed 75 g of oral glucose solution. Meal-stimulated insulin secretion was summarized as the mean plasma C-peptide from 90-270 minutes. This outcome measure was compared for each subject before treatment and after 2 months of insulin treatment to lower blood glucose. Subjects were started on 20 units of insulin glargine after their first visit and asked to measure their morning blood glucose daily. The dose of insulin was increased in increments of 4-6 units every 3 days targeting an average morning glucose level of less then 120 mg/dl. After 2 months of treatment the primary outcome was repeated with a second glucose clamp / oral glucose tolerance test, identical to the first.

Outcome measures

Outcome measures
Measure	Oral Glucose n=15 Participants Oral glucose administered to uncontrolled type 2 diabetic subjects.	IV Glucose n=15 Participants IV glucose administered to uncontrolled type 2 diabetic subjects.
Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. Insulin at baseline	546.9 pmol/L Standard Error 162.6	316.4 pmol/L Standard Error 59.0
Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. Insulin at 8 weeks	934.6 pmol/L Standard Error 282.2	395.6 pmol/L Standard Error 106.3

SECONDARY outcome

Timeframe: 2 months

Type 2 diabetic subjects had HbA1c measured before and after 2 months of basal insulin glargine treatment.

Outcome measures

Outcome measures
Measure	Oral Glucose n=15 Participants Oral glucose administered to uncontrolled type 2 diabetic subjects.	IV Glucose IV glucose administered to uncontrolled type 2 diabetic subjects.
HbA1c Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. HbA1c at baseline	8.6 % glycosylated hemoglobin Standard Error 0.2	—
HbA1c Before and After 2 Months of Insulin Treatment to Improve Average Glycemia. HbA1c at 8 weeks	7.1 % glycosylated hemoglobin Standard Error 0.2	—

Adverse Events

Arm 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David D'Alessio, MD, Section head, Endocrinology, Cincinnati VAMC

Cincinnati VAMC

Phone: 513-475-6478

Email: david.d'[email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place