Effect of Insulin Glulisine vs Regular Human Insulin on Postprandial Endothelial Function in Type 2 Diabetes

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the postprandial time course of nitrotyrosine after injection of insulin glulisine compared with regular human insulin. The secondary objectives are to evaluate the postprandial time course of the following efficacy parameters after injection of insulin glulisine compared with regular insulin on Blood Glucose Insulin Intact proinsulin Asymmetric dimethylarginine (ADMA) Metal matrix proteasis (MMP-9) Oxidative status (per ox) Interleukin 18 (IL-18) Free fatty acids (FFA) Oxidised LDL (ox-LDL) Microvascular blood circulation measured with laser Doppler at 37 °C (LDF37) Microvascular blood circulation measured with laser Doppler at 44 °C (LDF44)

Detailed Description
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Phase III b Indication Type 2 Diabetes Trial Objectives 1) Primary objective: The primary objective of the study is to evaluate the postprandial time course of nitrotyrosine after injection of insulin glulisine compared with regular human insulin. 2) Secondary objectives: The secondary objectives are to evaluate the postprandial time course of blood glucose, insulin, intact proinsulin, asymmetric dimethylarginine (ADMA), metal matrix proteasis (MMP-9), free fatty acids (FFA), oxidised LDL (ox-LDL), oxidative status (per ox), IL-18 as well as postprandial time course of microvascular blood circulation measured with laserdopplerflux at 37 °C (LDF37) and 44 C (LDF44). Efficacy Variables Primary efficacy variablePostprandial time course of nitrotyrosineSecondary efficacy variablePostprandial time course of glucose, insulin, intact proinsulin, ADMA, MMP-9, FFA, ox-LDL, per-ox, and IL-18 as well as postprandial time course of laserdopplerflux at 37 °C and 44 °C Safety Variables Incidence and frequency of adverse events and evaluation of safety laboratory parameters Medication/Dosage Insulin glulisine, dose 0.10 U/kg and Regular Human Insulin, dose 0.10 U/kg Study Duration Duration of study participation for one patient: 5 - 43 days Overall duration of the study: 6 months Design Single-centre, open label, randomized, 2-way-crossover trial Population Male and female type 2 diabetic patients between 40 and 70 years with HbA1c between 6.5 % and 9.9 % and treated with sulfonyurea alone or in combination with Metformin in a stable dosage within the last 3 months Sample Size N = 15

Official Title
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Effect of Prandial Treatment With Insulin Glulisine Compared to Regular Human Insulin on Postprandial Endothelial Function and Microvascular Stress in Type 2 Diabetic Patients

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Glulisine
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes mellitus according to the ADA criteria HbA1c between 6.5 % and 9.9 % Monotherapy with sulfonylurea or combined with Metformin in a stable dosage within the last 3 months Age between 40 and 70 years BMI < 40 Exclusion Criteria: Type 1 Diabetes mellitus Pre-Treatment with insulin within the last 6 months prior to screening Treatment with glitazones within the last 6 months prior to screening Pre-Treatment with PPARy-agonists, glinides 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) Hypokalemia (K < 3.5 mmol /l) Major micro- or macrovascular complications as judged by the investigator Tobacco use within the last 12 months prior to screening Drugs with major impact on endothelial function like nitrates etc. History of drug or alcohol abuse within the last five years prior to screening Anamnestic 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, > 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, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>One Day Treatment with Insulin Glulisine | Drug: Insulin Glulisine<br>* 100 IU/ml, 0.10 U/kg immediately before ingestion of a standardised liquid meal<br>* Other names: Apidra;|
| Active Comparator: 2<br>One day Treatment with Human insulin | Drug: Insulin<br>* 100 IU/ml, 0.10 U/kg 15 Minutes before ingestion of a standardised liquid meal<br>* Other names: Insuman;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the postprandial time course of nitrotyrosine after injection of insulin glulisine compared with regular human insulin |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postprandial time course of blood glucose, insulin, intact proinsulin, ADMA, MMP-9, FFA, ox-LDL, per ox Status, IL-18, postprandial time course of microvascular blood circulation measured with laserdopplerflux at 37 °C and 44 C |  | 1 day |