hypoxia-induced impairment of glucose homeostasis: sympathovagal imbalance and the potential therapeutic role of l/n type calcium channel blocker cilnidipine

Introduction: frequent occurrence of diabetes mellitus type 2 (t2dm) in patients with respiratory disease suggests a role of underlying chronic hypoxia (ch) in its pathogenesis. the present study aimed to delineate the link between ch, sympathovagal balance, and glucose homeostasis (gh) as well as to explore the role of l/n type calcium channel blocker, cilnidipine in alleviating ch-induced pathophysiology in experimental animals.methods: wister rats were divided into four groups: group i: control, (normoxia, 21%o2); group ii: chronic hypoxia (ch) (10%o2, 90%n2); group iii: normoxia+cilnidipine (cil, 2mg/kg/day); group iv: ch+cil (10%o2, 90%n2 + cil, 2mg/kg/day). sympathovagal balance was assessed by heart rate variability (hrv) analysis. glucose homeostasis was evaluated by fasting plasma glucose (fpg), fasting plasma insulin, oral glucose tolerance test (ogtt), homa-ir, and homa-β. the fasting lipid profile was also assessed.  results: ch increased lf (nu), lf/hf, and decreased hf (nu). additionally, ch increased fpg and homa-ir which were positively correlated with lf/hf and induced an atherogenic lipid profile. ogtt revealed normal 2h post-challenge glucose levels. in the cilnidipine-treated ch exposed group, lf (nu), hf (nu), and lf/hf were lower compared ch and glucose homeostasis parameters were comparable to control. conclusion: ch, by enhancing sympathetic activity, disturbs glucose homeostasis, leading to isolated impaired fasting glycemia (i-ifg), a prediabetic state. cilnidipine improved glucose homeostasis in ch-exposed experimental animals by ameliorating sympathetic hyperactivity with complementary effects on lipid profile, suggesting its utility as an adjunctive therapy against ch-induced t2dm.