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

Yin Y, Cheng Y, Zullo AR, Shao Y, Sheriff HM, Faselis C, Liu S, Ahmed A, Zeng-Treitler Q, Wu WC. Serum Magnesium, Prescribed Magnesium Replacement and Cardiovascular Events in Adults with Type 2 Diabetes: A National Cohort Study in U.S. Veterans. Nutrients. 2025 Jun 21; 17(13):DOI: 10.3390/nu17132067.

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Abstract:

OBJECTIVES: To investigate the relationship between serum magnesium levels, prescribed oral magnesium replacement, and major adverse cardiovascular events (MACE) in type-2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: This nationwide 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, ischemic stroke, or all-cause mortality) was determined using multivariable-adjusted Cox-regression models. Using a new-user-design and propensity-score-matching approach, 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 (serum magnesium > 2.3 mg/dL). Compared to patients with normomagnesemia (serum magnesium 1.8-2.3 mg/dL), those with either hypomagnesemia or hypermagnesemia had elevated hazards for MACE. The risk increased with the severity of serum magnesium abnormalities in both directions-low (hazard ratios [HRs] 1.11-1.20) and high (HRs 1.04-1.39)-in a parabolic pattern. 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% confidence interval [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.