Clinical trial NCT00742976: Effects of Insulin Detemir and NPH Insulin on Renal Handling of Sodium, Fluid Retention, and Weight in Type 2 Diabetic Patients
Official title: Effects of Insulin Detemir and NPH Insulin on Renal Handling of Sodium, Fluid Retention and Weight in Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Type 2
Weight Gain
Keywords: Weight gain in insulin treated type 2 diabetes
extracellular volume
insulin treatment
sodium retention
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2008-08-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: change in weight; change in extracellular volume
timeFrame: 17 weeks
Secondary outcomes:
measure: 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
timeFrame: 17 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Dept of Endocrinology, Rigshospitalet
state: København Ø
Study officials:
affiliation: Dept of Endocrinology at Rigshospitalet, Copenhagen.
name: Tonny Jensen, M.D MSci.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hendriksen KV, Jensen T, Oturai P, Feldt-Rasmussen B. Effects of insulin detemir and NPH insulin on renal handling of sodium, fluid retention and weight in type 2 diabetic patients. Diabetologia. 2012 Jan;55(1):46-50. doi: 10.1007/s00125-011-2345-8. Epub 2011 Oct 16.