Magnesium and hyperglycemia after kidney transplantation: A new target for treatment

Post-transplant (new onset) diabetes (PTDM) occurs in 10-15% of all patients undergoing kidney transplantation. Hypomagnesemia occurs in most of these patients due to use of calcineurin inhibitors and in some cases loop-diuretics. Both induce urinary excretion of magnesium. Furthermore, magnesium is central for normal function of the insulin receptor, and induced hypomagnesemia reduces both insulin secretion and action in normal persons. This project has three work packages:

Wp 1. We have a database of 1300 kidney transplant recipients who have undergone oral glucose tolerant tests (OGTTs) 8 and 52 weeks after transplantation. We will address whether hypomagnesemia 8 weeks after transplantation predicts fasting and post-challenge hyperglycemia 52 weeks after transplantation.

Wp 2. This is a cross-sectional study of kidney transplant recipients undergoing an OGTT 52 weeks after kidney transplantation with blood sampling for glucose, insulin and C-peptide measurements at 0,30 and 120 min after glucose intake. Through modelling we will assess whether low fasting magnesium levels are associated with impaired insulin release (1st phase and AUC) and/ or insulin resistance.

Wp 3. A 24-week randomized blinded study will be undertaken in 40 patients receiving either oral magnesium tablets or placebo. Only patients with measured magnesium <0,7 mmol/l will be included. The primary end-point will be the ability of retaining magnesium after  oral medication, assessed by an intravenous magnesium retention test before and after treatment. The secondary end-point will be change in glycemia as assessed by a 2-hr OGGT test with blood sampling for glucose, insulin and C-peptide every half hour.

This the PhD project of Rasmus Kirkeskov Carlsen, and will be completed in 2023.

News from 2022:
Wp 1 is completed and was presented at the annual meeting of European Renal Association and also the Eurpean Association for the Study of Diabetes in 2022. The manuscript will be submitted for publication

Wp 2: Data are collected and analyzed. Ready to be published.

Wp 3: The study is ongoing, and was delayed for recruitment due to the covid pandemic. It is expected to be finished in the fall of 2022.

Primary Investigator: Trond Jenssen, MD PhD, Professor of Medicine

Co-investigators/participants:  
Rasmus Kirkeskov Carlsen, MD, PhD Student
Anders Aasberg, Phd, Professor of Pharmacy
Kåre I. Birkeland, MD PhD, Professor of Medicine

External collaborators
My Svensson, MD PhD, Professor of Medicine, Akershus University Hospital
Iain Bressendorf, MD PhD, Hillerød Hospital, Denmark