Effects of Insulin Detemir and NPH Insulin on Renal Handling of Sodium, Fluid Retention, and Weight in Type 2 Diabetic Patients

Study Overview
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Brief Summary
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Hypothesis: Changing type 2 patients treatment from Insulin Insulatard to Insulin Detemir will increase their excretion of sodium in the urine and thereby decrease their extracellular volume and body weight. 24 patients are divided into 2 groups and their insulin treatment is shifted while their body composition, sodium excretion, weight and extracellular volume is monitored.

Detailed Description
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Type 2 diabetic patients experience weight gain when receiving insulin treatment. There has been reports that the weight gain is less or absent when patients are treated with Insulin Detemir. Patients with diabetes have increased total body sodium and increased extracellular volume. We hypothesize that part of the weight gain seen is due to increase in extracellular volume and that the lesser weight gain seen in patients treated with Detemir is due to an lesser increase in extracellular volume. We believe that the cause of this difference is the different pharmacokinetic properties of insulin Detemir. Insulin Detemir i protein bound and is therefore not excreted in the kidneys. This may cause less sodium reabsorption, than with other insulins, and therefore less increase in extracellular volume. We test this hypothesis by examining urinary sodium excretion, extracellular volume by GFR measurements, Body composition by DEXA scan, body weight, and 24 hour blood pressure.In patients that are changed from Insulin Insulatard to Insulin Detemir and back.

Official Title
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Effects of Insulin Detemir and NPH Insulin on Renal Handling of Sodium, Fluid Retention and Weight in Type 2 Diabetic Patients

Conditions
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Diabetes Type 2, Weight Gain

Intervention / Treatment
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* Drug: Insulin Detemir; Insulin Insulatard
* Drug: Insulin Detemir, Insulin Insulatard


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes according to WHO 1999 criteria for at least 3 month Insulin treated for at least 1 month BMI 25-40 Age 18-80 Hb1Ac < 10% Exclusion Criteria: Hypertension not well regulated Serum creatinine > 130 micromol/l Non-diabetic kidney disease Disease that may cause invalid hgbA1c measurement Substance abuse Recent use of Detemir Pregnancy or risk of becoming pregnant Any condition that may disturb protocol adherence (language barrier etc) urinary albumin > 30 mg/24hours ( before screening) Use of drugs that may influence blood glucose (except oral antidiabetics) Use of drugs that may influence sodium balance,i.e diuretics ( tiazides accepted) Clinical significant disease that may influence outcome ( cancer etc)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>8 weeks of insulin Detemir, then cross over to 8 Weeks of Insulatard, then cross over to 1 week of Detemir | Drug: Insulin Detemir, Insulin Insulatard<br>* Fixed doses in study period (if possible). Insulin Detemir once daily, Insulin Insulatard twice daily.<br>|
| Active Comparator: 2<br>8 weeks of Insulin Insulatard, then cross over to 8 weeks of insulin Detemir, then crossover to 1 week of Insulin Insulatard | Drug: Insulin Detemir; Insulin Insulatard<br>* Dosage is individual but fixed in study period (if possible). Detemir is given once daily, Insulatard is given twice daily.<br>Drug: Insulin Detemir, Insulin Insulatard<br>* Fixed doses in study period (if possible). Insulin Detemir once daily, Insulin Insulatard twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in weight; change in extracellular volume |  | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sodium excretion in urine, 24 hour blood pressure, body composition change,urine osmolality, urine albumin excretion, GFR, HbA1c, Blood lipid profile, NT-proBNP, plasma Albumin, Plasma metanephrines, aldosterone, active renin, angiotensin II |  | 17 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight gain in insulin treated type 2 diabetes, extracellular volume, insulin treatment, sodium retention