Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion

How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-β). Univariate linear regression analyses showed a correlation between PC2 and HOMA-β (β = −0.248, p < 0.0001), but not between PC1 and HOMA-β (β = −0.004, p = 0.9048). The correration between PC2 and HOMA-β persisted after adjustment for multiple factors (β = −0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-β (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35–2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population.