Effect of Treatment With Insulin VIAjectTM Compared to Regular Human Insulin and Insulin Lispro on Mealtime Blood Vessel Stress in Patients With Type 2 Diabetes Mellitus.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effects of insulin VIAject with Regular Human Insulin and Insulin Lispro on measures of mealtime blood vessel stress and blood flow.

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

Intervention / Treatment
-----------------
* Drug: Regular Human Insulin
* Drug: Insulin Lispro
* Drug: Insulin VIAject™ (75%)
* Drug: Insulin VIAject™ (90%)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes mellitus according to the ADA criteria HbA1c between 6.5 % and 9.9 % Treatment with sulfonylurea and/or metformin in a stable dosage within the last 3 months Age between 40 and 75 years BMI < 40 Exclusion Criteria: Type 1 diabetes mellitus Pre-treatment with insulin within the last 6 months prior to screening Pre-treatment with PPARy-agonists or glucosidase inhibitors within the last 4 weeks prior to screening Untreated hypertension stage II-III according to WHO criteria Planned or anticipated change in antidiabetic and/or concomitant medication during study participation Total cholesterol > 300 mg/dl (anamnestically) Major micro- or macrovascular complications as judged by the investigator Tobacco use within the last 6 months prior to screening Drugs with major impact on endothelial function like nitrates etc. History of drug or alcohol abuse which in the opinion of the investigator will impair subject safety or protocol compliance History of hypersensitivity to the study drugs or to drugs with similar chemical structures History of severe or multiple allergies Treatment with any other investigational drug within 3 months prior to screening Progressive fatal disease History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (creatinine > 1.1 mg/dL in women and > 1.5 mg/dL in men), neurological, psychiatric and/or haematological disease as judged by the investigator Pregnancy or breast feeding Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner Lack of compliance or other similar reason that at the discretion of the investigator precludes satisfactory participation in the study Hypopotassemia (K<3.5 mmol /l)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Regular Human Insulin<br>Single Injection | Drug: Regular Human Insulin<br>* 0.10 U/Kg- 15 minutes before ingestion of a standardized liquid meal.<br>|
| Active Comparator: Inuslin Lispro (90%)<br>Single Injection | Drug: Insulin Lispro<br>* 90% of Regular Human Insulin dose administer immediately before ingestion of a standardized liquid meal.<br>|
| Experimental: Insulin VIAject™ (75%)<br>Single Injection | Drug: Insulin VIAject™ (75%)<br>* 75 % of Regular Human Insulin dose administer immediately before ingestion of a standardized liquid meal<br>|
| Experimental: Insulin VIAject™ (90%)<br>Single injection | Drug: Insulin VIAject™ (90%)<br>* 90 % of Regular Human Insulin dose administer immediately before ingestion of a standardized liquid meal<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial time course of Asymmetric dimethyl arginine (ADMA) after injection of insulin VIAjectTM compared with regular human insulin and insulin lispro. |  | 0 - 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives are to evaluate the postprandial time course of arterial elasticity (pulse wave analysis; PWA), blood glucose, insulin, intact proinsulin, nitrotyrosine, glucagon, ICAM-1, VCAM, E-selectin. |  | 0 - 240 minutes |