(983) Cellular Oxygen Consumption in Patients With Diabetic Ketoacidosis

Introduction: Diabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid-base status. Mitochondrial dysfunction has been associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are both important factors in aerobic metabolism and have been found to be depleted in patients with DKA. In this study, we measured the cellular oxygen consumption rates (OCR) and the effects of in vitro administration of thiamine and CoQ10 on OCR in patients with DKA vs controls.

Methods: Blood samples were collected from a prospective cohort of patients with DKA (bicarbonate≤15 meq/L, anion gap>12, pH≤7.24 and ketonemia/uria) and controls from healthy volunteers. Basal and maximal cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after in vitro thiamine (0.5ug/mL), CoQ10 (1 ug/mL), and a combination of both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects.

Results: A total of 62 patients with DKA and 50 controls were included. Median basal and maximal OCRs were lower in DKA vs controls (basal 4.7 [IQR: 3.3, 7.9] vs 7.6 [4.9, 9.6]; maximal 16.4 [9.5, 28.1] vs 30.9 [20.5, 45.0] pmol/min/µg protein;p < 0.001). In patients with DKA, basal and maximal OCRs were higher in PBMCs treated with thiamine (basal median difference 0.76 [95% CI: 0.11, 1.41],p=0.02; maximal 2.54 [95% CI: 0.65, 4.44],p=0.009), CoQ10 (1.31 [95% CI: 0.33, 2.29],p=0.001; 3.75 [95% CI: 0.95, 6.56],p=0.009), or both (0.83 [95% CI: 0.03, 1.63], p=0.041; 3.48 [95% CI: 1.28, 5.70], p=0.003) compared to no treatment. In controls, basal OCR was higher when treated with thiamine and CoQ10; but there was no difference in maximal OCR with treatment.

Conclusions: Mitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of DKA patients treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefit in DKA via their metabolic effects on mitochondrial cellular respiration.