Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type?2 diabetes with sodium–glucose cotransporter?2 inhibitor: A randomized, open‐label, prospective study

摘要

Aims/Introduction Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium–glucose cotransporter?2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal–bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation. Materials and Methods This was a randomized, open‐label, 7‐day prospective study. Participants were type?2 diabetes patients with hyperglycemia, aged 20?years, with glycated hemoglobin 10%, daily mean preprandial blood glucose 11?mmol/L (200?mg/dL) and no previous antidiabetic medication. A total of 18 type?2 diabetes patients were randomized (1:1) to basal–bolus insulin titration algorithm (INS) alone or INS?+?dapagliflozin 5?mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry. Results The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal–bolus ratio ( P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post‐treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72?±?0.05 vs 0.79?±?0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group ( P 0.02). Conclusions INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid‐derived EE (failed to increase carbohydrate‐derived EE) and reduced basal insulin requirement might be related to further bodyweight loss.