Elevated Parathyroid Hormone Is Associated with an Increased Mortality Risk in Type 2 Diabetes

Parathyroid hormone (PTH) is one of the main regulators of calcium homeostasis. PTH levels are elevated in primary hyperparathyroidism as well as with vitamin D deficiency or chronic kidney disease. The association of increased PTH levels with all-cause mortality in high-risk patients is unclear. We therefore investigated the impact of serum PTH on mortality risk in a large series of 939 patients undergoing coronary angiography for the evaluation of established or suspected coronary artery disease (CAD), including 244 patients with type 2 diabetes (T2DM). Prospectively, deaths were recorded over a mean follow-up period of 6.2 years. PTH at baseline was inversely associated with eGFR (rho=-0.228; p<0.001) and 25-hydroxy-vitamin D (rho=-0.243; p<0.001) and was positively associated with age (rho=0.122; p<0.001) and BMI (rho=0.099, p=0.002). Prospectively, elevated PTH was not significantly associated with an increased mortality risk in the total study cohort (standardized HR 1.30 [0.96-1.76]; p=0.092). However, subgroup analysis with respect to T2DM showed a highly significant association of PTH with mortality in patients with T2DM (HR 2.32 [1.37-3.95]; p=0.002), but no association of PTH with mortality in nondiabetic subjects (HR 1.04 [0.82-1.32]; p=0.766). An interaction term T2DM x PTH was significant (p=0.006), indicating a significantly stronger influence of PTH on mortality risk in patients with diabetes than in individuals without T2DM. The impact of PTH on mortality risk in patients with T2DM remained significant after adjustment for age, gender, and BMI (HR 2.30 [1.34-3.93]; p=0.002) as well as after additional adjustment for, smoking, kidney function, baseline vitamin D and angiographically determined baseline CAD (HR 1.91 [1.07-3.40]; p=0.029). We conclude that elevated PTH levels are a strong and independent predictor of all-cause mortality in patients with T2DM.