TY - JOUR
T1 - Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type 2 diabetes with sodium–glucose cotransporter 2 inhibitor
T2 - A randomized, open-label, prospective study
AU - Kanazawa, Ken
AU - Uchino, Hiroshi
AU - Shigiyama, Fumika
AU - Igarashi, Hiroyuki
AU - Ikehara, Kayoko
AU - Yoshikawa, Fukumi
AU - Usui, Shuki
AU - Miyagi, Masahiko
AU - Yoshino, Hiroshi
AU - Ando, Yasuyo
AU - Kumashiro, Naoki
AU - Hirose, Takahisa
N1 - Funding Information:
Editorial assistance was funded by Ono Pharmaceutical Co., Ltd. (Osaka, Japan) and AstraZeneca K.K. (Osaka, Japan). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Takahisa Hirose received honoraria and research funding from Ono Pharmaceutical Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd. and Takeda Pharmaceutical Co., Ltd.; honoraria from Mitsubishi Tanabe Pharma Corporation, Kissei Pharmaceutical Co., Ltd., AstraZeneca K.K., Eli Lilly Japan K.K., MSD K.K. and Novartis Pharma K.K.; and research funding from Astellas Pharma Inc., Taisho Toyama Pharmaceutical Co., Ltd and Bayer Yakuhin, Ltd. Naoki Kumashiro received honoraria from Novo Nordisk Pharma Ltd. and research funding from Eli Lilly Japan K.K. Hiroshi Yoshino received research funding from Mitsubishi Tanabe Pharma Corporation. The remaining authors declare no conflict of interest.
Publisher Copyright:
© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd
PY - 2019/7
Y1 - 2019/7
N2 - 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. Clinical Trial Registry: National University Hospital Medical Information Network
UMIN000018997.
AB - 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. Clinical Trial Registry: National University Hospital Medical Information Network
UMIN000018997.
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U2 - 10.1111/jdi.12994
DO - 10.1111/jdi.12994
M3 - Article
C2 - 30582774
AN - SCOPUS:85068990377
VL - 10
SP - 1022
EP - 1031
JO - Journal of Diabetes Investigation
JF - Journal of Diabetes Investigation
SN - 2040-1116
IS - 4
ER -