Chapter 2 32 Association of ionized Mg with risk of developing T2D The baseline characteristics of the 5747 participants are shown in Table 2. Mean age was 53.0 ± 11.9 years, mean NMR-measured ionized Mg was 0.75 ± 0.05 mmol/L and 50.4% of the participants were female. Higher ionized Mg was associated with a slightly lower BMI, lower fasting glucose levels and higher HDL-cholesterol levels. In addition, subjects in the highest tertile of ionized Mg were more likely to be non-smokers. During a median follow-up period of 11.2 (IQR: 7.7-12.0) years, 289 (5.0%) participants developed T2D. We found an association between the levels of NMR-measured ionized Mg and the risk of developing T2D in the total population (HR: 1.50; 95% CI: 1.191.89). However, after multivariable adjustment, the association lost significance (HR: 1.16; 95% CI: 0.91-1.47). The association of NMR-measured Mg with risk of T2D was modified by sex (Pinteraction=0.007). In men, the association between NMR-measured Mg and risk of developing T2D was non-significant in the crude model (HR: 1.25; 95% CI: 0.94-1.67) and in a fully adjusted multivariable model (HR: 0.90; 95%: 0.67-1.21) (Table 3). In women, on the other hand, we found an association between NMR-measured Mg and the risk of developing T2D in the crude model (HR: 2.02, 95% CI: 1.37-2.99). After adjustment for lifestyle factors, including BMI, alcohol consumption, smoking status, triglyceride to HDL cholesterol ratio, use of antihypertensive drugs, and parental history of T2D (Model 1), the hazard ratio was slightly attenuated, but not substantially different (HR: 1.66; 95% CI: 1.11-2.47) (Table 3). When we further adjusted for the variables in Model 3, including fasting glucose, CRP and eGFR, the association remained similar (HR: 1.80; 95% CI: 1.20-2.70). Furthermore, the HR for women in the lowest tertile of NMR-measured Mg was 1.65 (95% CI: 1.02-2.66) in the crude analysis and 1.72 (95% CI: 1.03-2.86) after multivariable adjustment. A restricted spline curve confirmed the loglinear inverse association of NMR-measured Mg and risk of developing T2D in women (Figure 4).
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