Unilateral Primary Aldosteronism Lacking KCNJ5 Somatic Mutations is Associated with an Elevated Risk of New-Onset Diabetes Mellitus

The association between KCNJ5 mutations and the risk of developing new-onset diabetes mellitus (NODM) in patients with unilateral primary aldosteronism (uPA) remains underexplored. To investigate this association, we conducted a longitudinal study using data from the Taiwan Primary Aldosteronism Investigation database. Our sample included 360 uPA patients with adrenalectomies between 2012 and 2017, with 191 (53.1%) having KCNJ5 mutations in their adrenal adenomas. We found that uPA patients harboring KCNJ5 mutations had a higher rate of complete clinical success (69.5% vs. 43.8%, p < 0.01) and complete biochemical success (93.8% vs. 86.6%, P = 0.04) compared to those without KCNJ5 mutation at six months to one year after adrenalectomy. Over an average follow-up period of 8.5 years, multivariate Cox regression analysis revealed that uPA patients with KCNJ5 mutations had a significantly lower risk of developing NODM (hazard ratio [HR]=0.41; 95% confidence interval [CI], 0.17-0.996; p=0.049). Additionally, we identified higher body mass index (BMI) (HR=1.23; 95% CI, 1.11-1.37; p<0.01) and lower estimated glomerular filtration rate (eGFR) (HR=0.98; 95% CI, 0.97-0.99; p=0.01) as potential predictors of NODM based on baseline characteristics. The association between uPA patients without KCNJ5 mutations and higher incidence of NODM was less pronounced in subgroups characterized by younger age, higher BMI, higher eGFR, and lower potassium levels. In conclusion, uPA patients without KCNJ5 mutations have a higher incidence of NODM, with 13.6% affected during a long-term follow-up. Our findings suggest that uPA patients without KCNJ5 mutations may require more frequent follow-up for NODM after adrenalectomy.