Effect of intranasal insulin on osteocalcin levels and postoperative delirium in elderly patients undergoing joint replacement

Abstract

Background. Recently, intranasal insulin has shown great promise in preventing perioperative neurocognitive disorders through ameliorating insulin sensitivity and cognitive function. Whether osteocalcin, as a bone-derived hormone that can directly regulate insulin sensitivity and cognitive function, is linked to the mechanism of intranasal insulin remains ill-defined. Aims. To explore the effect of intranasal insulin on osteocalcin levels and the incidence and severity of postoperative delirium (POD) in elderly patients undergoing joint replacement. Methods. The study is designed as a randomized, double-blind, placebo-controlled clinical study. 212 elderly patients (≥65) were randomly assigned to receive either twice 40 IU insulin (n=106) or placebo (n=106). The incidence and severity of POD were estimated by the Confusion Assessment Method (CAM) and the Delirium Rating Scale (DRS)-98. The levels of total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC), insulin and glucose in venous blood and cerebrospinal fluid were detected by Enzyme-linked immunosorbent assay (ELISA). Insulin sensitivity was assessed by Homeostasis model Assessment of Insulin Resistance (HOMA-IR). The primary objective was to compare the difference of osteocalcin levels and insulin sensitivity between two groups, with the secondary objective to compare the difference of POD incidence and severity. Main Results. It showed that 8 patients (8.33%) occurred POD in insulin group within 5 days after surgery, significantly fewer than 23 patients (23.23%) in placebo group (P=0.004). Mean peak DRS in insulin group was significantly lower than that in placebo group (P<0.001). After intranasal insulin intervention of 3 days, levels of tOC and ucOC in cerebrospinal fluid were significantly elevated in insulin group at D0 (all P<0.001). Levels of tOC in plasma were significantly higher in insulin group than that in placebo group on D0, D1 and D3 (all P<0.001). Plasma ucOC level in insulin group was higher on D0, but lower on D1 and D3 than placebo group (all P<0.001). HOMA-IR was significantly lower on D3 in insulin group than placebo group (P=0.002). Conclusions. Intranasal insulin notably reduced the incidence and severity of POD in elderly patients undergoing joint replacement, and alco significantly improved central and peripheral osteocalcin levels and peripheral insulin sensitivity. Though these preliminary results needed further confirmation, it suggested that osteocalcin was promisingly involved in the mechanism of intranasal insulin in improving insulin sensitivity and POD. Trial registry numbers. Chinese Clinical Trial Registry (ChiCTR2300068073)