The Impact of Magnesium Supplementation on Insulin Resistance and Secretion in Renal Transplant Recipients

Study Overview
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Brief Summary
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Hypomagnesemia is common in renal transplant recipients and is mainly because of enhanced renal magnesium wasting, caused by immunosuppressive drugs (calcineurin inhibitors). Glucose metabolism disorders, including insulin resistance and decreased insulin secretion, are also prevalent post-transplantation and often precede the development of diabetes. As magnesium supplementation has been demonstrated to increase insulin sensitivity in both diabetic and non-diabetic patients, its potential therapeutic supplementation (post-transplantation) deserves further examination. The hypothesis is that magnesium supplementation in renal transplant recipients exerts a beneficial effect on insulin resistance and/or secretion.

Official Title
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The Impact of Magnesium Supplementation on Insulin Resistance and Secretion in Renal Transplant Recipients

Conditions
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Glucose Metabolism, Renal Transplantation

Intervention / Treatment
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* Dietary Supplement: magnesium supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplantation recipients > 18 years of age more than 4 months post-transplantation Hypomagnesemia < 1,8 milligram/deciliter on 2 consecutive blood samples (laboratory reference interval 1,7 - 2,55 milligram/deciliter) at least 1 month apart. Exclusion Criteria: Pre-existing diabetes mellitus defined as the intake of anti-diabetic drugs at the time of inclusion Biopsy that proves acute rejection and consecutive treatment with corticosteroid boluses less than 2 months before inclusion Serum creatinine > 3 milligram/deciliter Active infection (C reactive protein > 3 milligram/deciliter) Severe hypomagnesemia (< 1,2 milligram/deciliter) Hypokalemia (< 3,5 milli-equivalent/liter) Severe hypocalcemia (< 6,5 milligram/deciliter) Intake of digoxin Intake of magnesium supplementation up to 2 weeks before randomization.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hypomagnesemic + magnesium supplement<br>The patient group of hypomagnesesemic renal transplant recipients randomized to magnesium supplementation (number = 30). The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion,which are repeated after 6 months. | Dietary Supplement: magnesium supplementation<br>* The supplementation starts with 450 mg of magnesium oxide daily, up to a maximum of 3 times 450 mg daily, while aiming at a serum magnesium level of > 1,9 mg/dl.<br>|
| No Intervention: hypomagnesemic without magnesium supplement<br>The patient group of hypomagnesesemic renal transplantation recipients, randomized to no magnesium supplementation (number = 30). During 6 months, no magnesium supplementation is started, provided that the serum magnesium level remains > 1,2 milligram/deciliter. In case of cramps, intermittent supplementation is allowed, but will be recorded. The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion,which are repeated after 6 months. | |
| No Intervention: normomagnesemic without magnesium supplement<br>In the control group of normomagnesemic renal transplantation recipients (number = 10), only a baseline assessment will be performed. The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of change in insulin resistance/secretion | The primary outcome of the study is the evaluation of change in insulin resistance and insulin secretion after 6 months of supplementation (versus no supplementation). Insulin resistance is measured by 'Homeostatic Model Assessment' (HOMA) - modeling and the McAuley Index. Insulin secretion is assessed by 'Oral Glucose Tolerance test' (OGTT)- derived indices. | after 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of change in Hemoglobin A1c (HbA1C) | The secondary outcome is the evaluation of change in Hemoglobin A1c after 6 months of magnesium supplementation versus no supplementation. | after 6 months |