High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan

Abstract

To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA 1c ] ‡6.5% [ ‡48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ‡1.8 mg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% £ HbA 1c <6.5% [39 mmol/mol £ HbA 1c <48 mmol/mol]) were examined. RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or x 2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA 1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

“…One further mechanism underlying the impairment in glucose metabolism in PA is glucocorticoid co-secretion. Although recent studies showed that higher prevalence of DM in PA patients might be associated mainly with SH [27,28], our result showed PA patients without SH, and thus with aldosterone excess alone, had a higher prevalence of DM than do sex-, age-, and BMI-matched controls. Interestingly, the DM prevalence and FPG levels were significantly decreased after ADX in PA patients without SH.…”

“…Third, findings regarding parameters to assess glucose metabolism in PA were not fully consistent [16,[21][22][23][24][25][26]. Fourth, recent studies showed that possible cortisol co-secretion rather than only aldosterone excess itself could contribute to the impairment of glucose metabolism in patients with PA [27,28]. Finally, comparisons of the effects of adrenalectomy (ADX) and mineralocorticoid receptor antagonist (MRA) therapy on glucose metabolism in PA have only sparsely been studied.…”

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome

“…The proportions of DM patients in the PA and SCS groups increased, which resulted to nullify a statistically significant difference in the proportion of DM patients between the 2 study groups. The fact that the risk for DM is increased in PA patients with mild glucocorticoid excess has been reported [30][31][32]; the finding was also described in Japanese patients with PA and patients with PASCS [33].…”

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

“…Using data from a nationwide PA registry (the Japan Primary Aldosteronism Study [JPAS] and Japan Rare/Intractable Adrenal Diseases Study [JRAS]), 7,10,11 we assessed whether changes in circulating aldosterone levels and BP were associated with changes in eGFR after surgical or MR antagonist treatment, respectively.…”