I3LTE4: Intensive Insulin Therapy and Production of LTE4 in Patients With Diabetes

Study Overview
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Brief Summary
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The primary objective of the study is to assess the effect of a 3-month intensive insulin therapy on urinary leukotriene E4 (LTE4) excretion in patients with diabetes.

Detailed Description
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Our group has recently reported the results of a preliminary cross-sectional study, which demonstrated that the urinary LTE4 excretion is increased in patients with type 1 diabetes. With regard to recent human genetic studies showing that polymorphisms in the 5-lipoxygenase (5-LO) promoter and FLAP haplotypes is linked to cardiovascular disease susceptibility our data suggested the potential interest of LTE4 as a non-invasive biomarker of cardiovascular risk. In diabetes mellitus, further studies are required to evaluate the 5-LO pathway after improvement of glucose control and concomitantly with established inflammatory cardiovascular biomarkers. The secondary objectives are: Before and after 3-month intensive insulin therapy- Relationship between a marker of platelet activation (urinary 11-dehydro-thromboxan B2 :11-dehydroTXB2) and urinary LTE4- Relationship between inflammatory plasma markers of cardiovascular risk (hs-CRP and fibrinogen) and urinary LTE4- Relationship between a plasma marker of endothelial dysfunction (sICAM-1) and urinary LTE4- Changes in LTE4 according to patient subgroups (patients with type 1 and type 2 diabetes mellitus)

Official Title
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Effect of an Intensive Insulin Therapy on the Production of LTE4 in Patients With Diabetes

Conditions
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Diabetes Mellitus, Leucotrienes

Intervention / Treatment
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* Drug: intensive insulin therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diabetes mellitus (type 1 or type 2) > 18 year-old subject has given free, informed written consent subject entitled to health insurance cover medical follow-up at the department of Diabetology, Grenoble University Hospital inappropriate glucose control (HbA1c > 8.5%) requiring an initiation, or revision, of insulin therapy Exclusion Criteria: legal incapacity or limited legal competence pregnant women heart failure impaired renal function,defined by a creatinin clearance < 60 ml/mn according to Cockroft formula asthma respiratory failure IV, IM, SC or oral treatment with cortico-steroids for the last 2 months prior to baseline current smoking > cigarettes / day any infectious disease for the last 2 months prior to baseline baseline CRP > 20 mg/l

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: intensive insulin therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in urinary LTE4 excretion and HbA1c after 3-month intensive insulin therapy versus baseline |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urinary 11-dehydroTXB2 |  |  | 
| hs-CRP |  |  | 
| fibrinogen |  |  | 
| sICAM-1 plasma levels |  |  |