Magnesiumerstatning og høyt blodsukker etter nyretransplantasjon

Lav magnesium er assosiert med diabetes type 2, og muligens også diabetes etter organtransplantasjon (posttransplantasjonsdiabetes=PTDM). Magnesiumtilskudd er tilgjengelig som tabletter. Det er usikkert om magnesium fra tabletter tas opp i kroppen i særlig grad, og bare 0,3% av kroppens magnesium sirkulerer i blodet. Vi vil undersøke om tablett-tilskudd hjelper som magnesiumtilførsel hos nyretransplantert med lav magnesium i blodet (laver enn 0,7 mmol/l).

Randomized double-blind placebo-controlled trial. Subjects with hypomagnesemia (< 0.7 mmol/L) not treated with hypoglycemic agents for diabetes will be eligible for inclusion.

Subjects will be randomized 1:1 to receive either oral magnesium supplementation (Mablet 360 mg) or placebo. Subjects will be randomized using variable blocks in a 1:1 ratio to either magnesium supplementation or matching placebo. Randomization will be performed using computer software (the blockrand package for R) to create consecutively numbered envelopes and a randomization list. The randomization list will be kept in a locked filing cabinet behind a locked door at the department of Transplantation Medicine at Oslo University Hospital Rikshospitalet.

Subjects will meet for a midterm control at Rikshospitalet at 12 weeks and be contacted by telephone at 4 and 18 weeks to control compliance and adverse events. 

Mablet will be ingested twice daily for 4 weeks. If tolerated, doses will be increased to 360 mg trice daily for further 20 weeks. 

Subjects will meet at the Laboratory for Renal Physiology, Oslo University Hospital – Rikshospitalet at 0 and 24 weeks treatment with the following sequential tests:

1. An OGTT with 0, 30 and 120 min measurements of glucose, insulin and C-peptide.
2. An intravenous magnesium loading test
3. 24 hour urine will be collected from the start of the loading test for analysis of urine magnesium, creatinine and albumin.

Loading test will be performed with an infusion of 30 mmol magnesium sulphate in 1000 mL 0.9% NaCl solution, administered through a peripheral venous catheter over 8 hours at 125 ml/hour. A blood sample will be drawn 60 minutes after the start of infusion to measure of peak plasma magnesium. Twenty-four hours of continuous urine will be collected from the start of the loading test for calculation of magnesium retention.

Based on preliminary data we expect a difference in magnesium retention of 2 mmol/d (standard deviation ± 2) from baseline to 24 weeks treatment between subjects with oral magnesium supplementation and subjects with placebo. With a power of 80%, a significance level of 5 % and a dropout of 20% the study will require a total of 40 participants.   

Primary endpoint: Magnesium retention and content.

Magnesium retention is defined as urine magnesium excretion during the 24 hours post magnesium infusion controlled for urine creatinine and together divided by infused magnesium sulphate. 

Secondary endpoints: Area under the curve (AUC) for insulin and glucose, 1^st and 2^nd phase insulin insulin release according to the Stumvoll equation¹, insulin secretion evaluated by insulinogen index², insulin sensitivity assessed  by Matsuda index³, HOMA-index of fasting blood samples⁴.

1.         Stumvoll et al. Diabetes Care 2000; 23: 295-301.

2.         Seltzer et al. J Clin Invest 1967; 46: 323-335.

3.         Matsuda M, DeFronzo RA. Diabetes Care 1999; 22: 1462-1470.

4.         Matthews et al.  Diabetologia 1985; 28: 412-419.

40 personer vil motta blindet behandling med magnesiumtabletter eller placebo (narretabletter), 20 personer i hver gruppe. Kroppens magnesiumbeholdning vil bli undersøkt ved at man får 30 mmol magnesium intravenøst før behandlingen starter, og på nytt etter 24 ukers behandling. Man samler urin i ett døgn etter magnesiuminfusjonen for å se hvor mye magnesium kroppen skiller ut i urinen. Dersom man skiller ut mye magnesium, betyr det at kroppen er fullastet med magnesium. Dersom man skiller ut lite magnesium betyr det at man har lite magnesium ("kroppen holder igjen"). Hypotesen er A. At de med lavt magnesium i blodet har magnesiummangel ved forsøkets start. B. At de som får magnesiumtabletter har mer magnesium i kroppen ved forsøkets slutt enn de som får placebo. I tillegg gjøres det en sukkertest (man inntar sukkervann og måler blodsukkeret) ved forsøkets start og ved forsøkets avslutning.