Characteristics of Glargine in Type 2 Diabetics

Study Overview
=================
Brief Summary
-----------------
The study is to determine the dose response relationship of insulin glargine in type 2 diabetes over a 24-hour period and measuring the differences in glucose production among the differing doses of glargine. Hypothesis: Differing doses of insulin glargine over a 24-hour period in type 2 diabetes will show differing effects on endogenous glucose production, glucose disposal and carbohydrate and lipid flux.

Detailed Description
-----------------
The incidence of type 2 DM is increasing worldwide at an alarming rate. Unfortunately, the number of individuals with glycemic control at or below the American Diabetes Association goal of 7% has dropped. In fact, the number of patients with their important cardiometabolic risk factors of glucose, lipids and blood pressure at goal is only 7%. One of the reasons for this lack of metabolic control in type 2 DM is the continued relative underutilization of insulin. Diabetes is an insulin deficient state and requires appropriate physiologic replacement of insulin. Physiologic replacement of insulin requires a basal component to restrain overnight endogenous glucose production, lipolysis and proteolysis. The other component involves prandial insulin to regulate post prandial glucose levels. Recently, insulin glargine was introduced as a once-a-day peakless basal insulin. This form of basal insulin reproduces the normal constitutive physiologic release of insulin from the pancreas. Insulin glargine represents a breakthrough in treatment as the previous available basal insulins either produced peaks of activity (which are disadvantageous as this results in hypoglycemia) or do not last 24 hrs which results in post absorbative hyperglycemia. Despite the undoubted advantages of insulin glargine, there remains a lack of information regarding some aspects of glargine action. The study objectives are: 1) to determine the pharmacokinetic and pharmacodynamic dose response relationship of insulin glargine in Type 2 DM; 2) partition the dose response relationship of insulin glargine on endogenous glucose production and glucose uptake in Type 2 DM; and 3) to determine if the pharmacokinetic and pharmacodynamics of insulin glargine are consistent over a wide range of doses.

Official Title
-----------------
A Comparison of PK/PD Dose Response Characteristics of Glargine in Type 2 Diabetics

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Insulin Glargine 0.5 u/kg body wt SC
* Drug: Insulin Glargine 1.0 u/kg body wt SC
* Drug: Insulin Glargine 1.5 u/kg body wt SC
* Drug: Insulin Glargine 2.0 u/kg body wt SC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 12 adults (males or females) with type 2 diabetes for at least six (6) months. May be using oral agents (SUs, metformin, acarbose or glitinides) with or without insulin. HgbA1c 7 -12% Age 18-70 years BMI 27-40 kg/m² Exclusion Criteria: Any past or present clinically relevant abnormality, medical condition, or circumstance making the subject unsuitable for participation in the study Evidence of hepatic, renal or cardiac failure Abnormal results following screening tests Pregnant or lactating females or females of childbearing potential who are unwilling to abstain from sexual intercourse or use reliable, medically accepted methods of contraception Currently using TZDs History of alcoholism or drug abuse within 12 months of the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo then Insulin Glargine<br>Placebo: administer single dose of Placebo subcutaneously (SC) with blood glucose monitoring over 24 hours. Then Insulin Glargine SQ 8 weeks later, in increasing doses (0.5, 1.0, 1.5, 2.0 u/kg body wt.) with blood glucose monitoring monitoring over a 24 hour period. Each dose is separated by 8 weeks (5 separate study visits) | Drug: Placebo<br>* single dose of Placebo injected s/c at 8am and monitor blood glucose over 24 hours<br>* Other names: Lantus;Drug: Insulin Glargine 0.5 u/kg body wt SC<br>* 8 weeks later, a differing dose (0.5, 1.0, 1.5, 2.0 u/kg body wt.) of Insulin Glargine and monitoring over a 24 hour period each separated by 8 weeks (5 separate study visits)<br>* Other names: Lantus;Drug: Insulin Glargine 1.0 u/kg body wt SC<br> <br> * Other names: Lantus;Drug: Insulin Glargine 1.5 u/kg body wt SC<br> <br> * Other names: Lantus;Drug: Insulin Glargine 2.0 u/kg body wt SC<br> <br> * Other names: Lantus;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Glucose Infusion Rate | measuring the changes in glucose infusion rate during the 24 hour experimental period. | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 diabetes, Insulin Glargine, Endogenous Glucose Production