Severe Insulin Resistance in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to investigate some of the mechanisms behind severe insulin resistance and to determine the dose response to insulin in patients with type 2 diabetes mellitus.

Detailed Description
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Overnutrition and obesity are pivotal to the metabolic syndrome and diabetes. The sedentary lifestyle and overly rich nutrition are predominant in Western societies and result in obesity, insulin resistance and type 2 diabetes mellitus. According to the WHO an escalating global epidemic of overweight and obesity is sweeping the globe and the prevalence of type 2 diabetes mellitus rises in parallel at the same alarming rate. It is likely that inherited insulin resistance relates to subtle mutations in many metabolic genes. It is still unclear whether such abnormalities lead to different proteomic patterns in target tissues (muscle and fat) and how intracellular hormone signaling is affected. Some patients with type 2 diabetes mellitus have severe insulin resistance with insulin requirements of more than 100 units/day and are still not optimally controlled. Our aim of this study is to examine the mechanisms behind severe insulin resistance and to elucidate how intracellular hormone signaling is affected, especially in relation to proteomics. Moreover we wish to determine the dose response to insulin in patients with type 2 diabetes mellitus with severe insulin resistance in order to see if there is a measurable effect on blood glucose at high insulin doses.

Official Title
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Severe Insulin Resistance in Patients With Type 2 Diabetes: Mechanisms Behind Insulin Resistance.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Actrapid (human insulin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-75 years old BMI between 25 and 42 Exclusion Criteria: Severe diseases

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L1<br>Actrapid infusion, 0.5 mU/kg/min. | Drug: Actrapid (human insulin)<br>* On day one: 0,5 IU/kg/min for 3 hours, 1,5 IU/kg/min for 3 hours, on day two: 3,0 IU/kg/min for 3 hours, 5,0 IU/kg/min for 3 hours<br>|
| Experimental: L2<br>Actrapid infusion 1.5 mU/kg/min | Drug: Actrapid (human insulin)<br>* On day one: 0,5 IU/kg/min for 3 hours, 1,5 IU/kg/min for 3 hours, on day two: 3,0 IU/kg/min for 3 hours, 5,0 IU/kg/min for 3 hours<br>|
| Experimental: H1<br>Actrapid infusion 3.0 mU/kg/min | Drug: Actrapid (human insulin)<br>* On day one: 0,5 IU/kg/min for 3 hours, 1,5 IU/kg/min for 3 hours, on day two: 3,0 IU/kg/min for 3 hours, 5,0 IU/kg/min for 3 hours<br>|
| Experimental: H2<br>Actrapid infusion 5.0 mU/kg/min | Drug: Actrapid (human insulin)<br>* On day one: 0,5 IU/kg/min for 3 hours, 1,5 IU/kg/min for 3 hours, on day two: 3,0 IU/kg/min for 3 hours, 5,0 IU/kg/min for 3 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity |  | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in insulin signaling proteins? |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Severe insulin resistance