Effects of Insulin Detemir and NPH Insulin on Renal Handling of Sodium, Fluid Retention, and Weight in Type 2 Diabetic Patients (Le-Na)

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

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

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.

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.

Weight gain in insulin treated type 2 diabetes, extracellular volume, insulin treatment, sodium retention

8 weeks of insulin Detemir, then cross over to 8 Weeks of Insulatard, then cross over to 1 week of Detemir

8 weeks of Insulin Insulatard, then cross over to 8 weeks of insulin Detemir, then crossover to 1 week of Insulin Insulatard

Dosage is individual but fixed in study period (if possible). Detemir is given once daily, Insulatard is given twice daily.

Fixed doses in study period (if possible). Insulin Detemir once daily, Insulin Insulatard twice daily.

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

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)

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.