Insulin Secretion in Diabetes Before and After Glycemic Control

NCT00469833 | Completed Results

• 1 other identifier: ENDA-010-06S
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this project is to understand defects in insulin secretion that contribute to abnormal glucose metabolism in patients with diabetes. In particular the effects of signals released from the intestine to stimulate insulin secretion will be tested. Patients with type 2 diabetes will have insulin secretion in response to glucose and intestinal factors before and after insulin treatment to lower their blood glucose. It is expected that the results of this work will provide valuable information for treating diabetic people.

Conditions

Diabetes; Hyperglycemia

Keywords

Diabetes; Glucose Tolerance; Incretin; Insulin

Outcome Measures

Primary Outcomes (3)

• ISR in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

  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.

  180 minutes

• 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.

  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.

  180 minutes

• Insulin Concentration in Response to a Glucose Clamp and Oral Glucose Ingestion Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

  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.

  180 minutes

Secondary Outcomes (1)

• HbA1c Before and After 2 Months of Insulin Treatment to Improve Average Glycemia.

  2 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Intervention: Insulin glargine treatment. The study is designed as a within subjects comparison of insulin secretion in type 2 diabetic patients before and after 2 months of insulin treatment to reduce blood glucose. Insulin secretion will be determined with a hyperglycemic clamp using 20% dextrose, and ingestion of an oral glucose solution (75 g).

Drug: insulin glargine

Interventions

insulin glargine DRUG

Diabetic subjects will be treated with insulin glargine once daily for 2 months. Subjects will monitor their blood glucose and have their insulin dose adjusted in steps of 4-6 units to achieve a goal of less than or equal to 120 mg/dl for fasting blood glucose.

Also known as: Basal insulin, Long-acting insulin, Lantus

Arm 1

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aim 1:
• (non-diabetics)
• male/female 30-65 yrs old,
• free of active medical disease,
• no history of diabetes.
• (diabetics)
• HbA1c=6.5-8.5,
• treated with metformin, a sulfonylurea, or combination,
• Stable body wt with BMI 28-40.
• Aim 2: Same as above
• Aim 3: Diabetic with HgA1c 8.0-9.5

You may not qualify if:

• Aim 1: For both groups: no history of: pancreatitis, cardiac, gastrointestinal, renal or liver disease.
• Aim 2: Same as above
• Aim 3: Same as above, plus a diagnosis of incipient diabetic nephropathy severe nonproliferative, or proliferative retinopathy.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (1)

VA Medical Center, Cincinnati

Cincinnati, Ohio, 45220, United States

Location

Related Publications (1)

• An Z, Prigeon RL, D'Alessio DA. Improved glycemic control enhances the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2013 Dec;98(12):4702-8. doi: 10.1210/jc.2013-1199. Epub 2013 Oct 3.

  PMID: 24092826 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Hyperglycemia; Insulin Resistance

Interventions

Insulin Glargine; Insulin, Long-Acting

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Two subjects could not complete the initial assessment due to poor IV access. All 15 subjects who completed the initial assessment and were started on insulin completed the study. There were no significant adverse events.

Results Point of Contact

• Title: David D'Alessio, MD, Section head, Endocrinology, Cincinnati VAMC
• Organization: Cincinnati VAMC

david.d'alessio@va.gov

513-475-6478

Study Officials

• David D'Alessio, MD

  Cincinnati VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2007
• First Posted: May 7, 2007
• Study Start: April 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: September 1, 2012
• Last Updated: January 15, 2015
• Results First Posted: January 15, 2015

Record last verified: 2015-01

Locations

US (1)