Sodium Bicarbonate Treatment Promotes Hypoxia and Insulin Resistance in Rats

Background: The Use of Bicarbonate in Chronic Renal Insufficiency (UBI) study, found that the relationship between serum bicarbonate and HOMA-IR in patients treated with sodium bicarbonate is non-linear. That is, while HOMA-IR decreased in patients with serum bicarbonate between 24-28mmol, HOMA-IR increased in patients with levels above 28mmol/L. The mechanisms underlying the divergent responses in the UBI study remain unclear. Chronic intermittent hypoxia has been reported to promote loss of insulin sensitivity. As metabolic alkalosis from high serum bicarbonate may slow respiratory rate, in the current study we hypothesized that sodium bicarbonate treatment may promote hypoxia and insulin resistance in rats with CKD Methods: Male Sprague Dawley rats were used (n=9-3 per group). Rats underwent either surgical incision 5/6 nephrectomy surgery or sham surgery and were allowed to recover for 8 weeks before performing a baseline insulin tolerance test (ITT). Rats were then randomly divided into treatment groups to receive either 0.1M NaHCO3 in the drinking water (Bicarbonate treatment) or tap water 2 weeks. At the end of the treatment period, blood was collected from the tail vein for analysis (PrimeVet blood gas analyzer) and a repeat ITT performed Results: Rats in the CKD group had significantly higher plasma creatinine and BUN when compared to rats in the sham group (p<0.01). Plasma HCO3- was significantly elevated in both sham and CKD bicarbonate treated rats compared to rats receiving tap water (P=0.02). Consistent with bicarbonate treatment promoting hypoxemia and tissue hypoxia, plasma lactate was significantly elevated in both sham and CKD bicarbonate treated rats when compared to rats receiving tap water (p=0.02). Hematocrit and total hemoglobin also tended to be elevated following bicarbonate treatment. Fasted glucose levels were significantly elevated in both sham and 5/6 Nx rats following bicarbonate treatment (p=0.01). ITT identified reduced insulin sensitivity in both sham and 5/6 Nx rats following 2 weeks of bicarbonate, but not tap water treatment. Conclusion: Our data indicate that bicarbonate loading can promote both hypoxia and worsen insulin sensitivity in rats. We speculate that increases in HOMA-IR in CKD patients receiving bicarbonate with plasma HCO3- above 28mmol/L may be due to insulin resistance secondary to pH mediated decreases in respiratory rate and intermittent hypoxemia. Funding: NIDDK Support, Private Foundation Support