Serum Magnesium, Prescribed Magnesium Replacement and Cardiovascular Events in Adults with Type 2 Diabetes: A National Cohort Study in U.S. Veterans.

Objective: To investigate the relationship between serum magnesium levels, prescribed oral magnesium replacement, and major adverse cardiovascular events (MACE) in type-2 diabetes (T2D).

Methods: This national-wide retrospective study analyzed 1,284,940 US Veterans (≥18 years) with T2D who had outpatient serum magnesium testing between 1999-2021 in the Veterans Health Administration. The relationship between serum magnesium levels and MACE (hospitalizations for acute myocardial infarction, heart failure, or ischemic stroke, or all-cause mortality) was determined using multivariable-adjusted Cox-regression models. Using a new-user-design and propensity-score-matching analysis, we further related the use of prescribed oral magnesium and MACE among patients with hypomagnesemia (serum magnesium <1.8 mg/dL) and normomagnesemia (serum magnesium 1.8-2.3 mg/dl).

Results: Of 1,284,940 patients with T2D, 229,210 (17.8%) patients had hypomagnesemia, and 117,674 (9.2%) patients had hypermagnesemia. Both hypomagnesemia and hypermagnesemia (serum magnesium >2.3 mg/dL) were linked to higher MACE risks (HRs 1.11-1.20 for hypo-and 1.04-1.39 for hypermagnesemia, respectively) compared to normomagnesemia. Oral magnesium was prescribed to 9.7% and 0.7% of patients with hypomagnesemia and normomagnesemia, respectively. After propensity-score-matching balanced across 64 baseline characteristics, oral magnesium was associated with a lower MACE risk in 40,766 matched patients with hypomagnesemia (HR 0.89; 95%CI, 0.84-0.93), especially those on proton-pump-inhibitors or thiazides. Oral magnesium was not related to MACE in 11,838 matched patients with normomagnesemia (HR 1.07; 95%CI, 0.97-1.17).

Conclusions: In patients with T2D, both hypomagnesemia and hypermagnesemia were associated with higher one-year MACE risks compared to normomagnesemia. Prescribed oral magnesium was associated with a reduced MACE risk in hypomagnesemia but not in normomagnesemia.