Hypomagnesemia is Associated with New-onset Diabetes Mellitus following Heart Transplantation

Purpose: Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium (Mg) deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT).

Methods: Between 2002 and 2017 we assessed 101 non-DM HT patients. S-Mg levels were reviewed during the first year post-HT. In accordance with the mean value of all s‑Mg levels recorded during the first year, patients were divided into high s-Mg (≥1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association: hemoglobin A1c ≥6.5%; fasting plasma glucose ≥126 mg/dL; or random plasma glucose ≥200 mg/dL.

Results: Baseline clinical and demographic characteristics for the high s-Mg (n=42) and low s-Mg (n=59) groups were similar. Kaplan-Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high s-Mg vs low s-Mg (84% vs 22% log-rank test, p=0.003, Figure). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies and mean creatinine values of the first year post-HT, showed that low s-Mg was independently associated with a significant >5-fold increased risk for NODAT (95% CI 1.35-21.04, p=0.02). Patients with low s-Mg levels had a significantly higher rate of cerebrovascular events than patients with high s-Mg (15.5% vs 0, p=0.02).

Conclusions: Low post-HT s-Mg level is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, on the risk for NODAT and on clinical outcomes should be evaluated.