Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation

Abstract

Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.

Keywords: diabetes mellitus; hypomagnesemia; kidney transplantation.

Figure 1.

Study flow diagram showing the results of applying exclusion criteria to the cohort of patients eligible for study inclusion.

Figure 2.

Kaplan–Meier curves for NODAT using different approaches to analyze Mg levels post-transplant. Cumulative probabilities of NODAT by (A) serum Mg at 1-month post-transplant; (B) average serum Mg over the first month post-transplant; (C) time-varying serum Mg updated at 3-month intervals; and (D) rolling-average time-varying serum Mg assessed over 3-month exposure windows.

Figure 3.

Fractional polynomial plots for the risk of NODAT using different approaches to analyze Mg levels post-transplant. Log hazard ratios for NODAT by (A) serum Mg at 1-month post-transplant; (B) mean serum Mg over the first month post-transplant; (C) time-varying serum Mg updated at 3-month intervals; and (D) rolling-average time-varying serum Mg assessed over 3-month exposure windows.