PMID- 28099783
OWN - NLM
STAT- MEDLINE
DCOM- 20180426
LR  - 20220317
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Linking)
VI  - 33
IP  - 5
DP  - 2017 Jul
TI  - Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic 
      mechanisms and therapeutic perspectives.
LID - 10.1002/dmrr.2886 [doi]
AB  - Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of 
      antihyperglycemic drugs that have been approved for the treatment of type 2 
      diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the 
      proximal tubules of the kidney thereby enhancing glucosuria and lowering blood 
      glucose levels. Additional consequences and benefits include a reduction in body 
      weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have 
      protective effects on the kidney and cardiovascular system in patients with T2DM 
      and high cardiovascular risk. However, a potential side effect that has been 
      reported with SGLT2 inhibitors in patients with T2DM and particularly during 
      off-label use in patients with type 1 diabetes is diabetic ketoacidosis. The US 
      Food and Drug Administration recently warned that SGLT2 inhibitors may result in 
      euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, 
      the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 
      inhibitors may facilitate the development of ketosis or ketoacidosis. This 
      provides the rationale for measures to lower the risk. We discuss the role of the 
      kidney and potential links to renal gluconeogenesis and uric acid handling. 
      Moreover, we outline potential beneficial effects of modestly elevated ketone 
      body levels on organ function that may have therapeutic relevance for the 
      observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular 
      system.
CI  - Copyright (c) 2017 John Wiley & Sons, Ltd.
FAU - Qiu, Hongyu
AU  - Qiu H
AD  - Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, P. R. China.
AD  - Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, 
      University of California San Diego, San Diego, CA, USA.
FAU - Novikov, Aleksandra
AU  - Novikov A
AD  - Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, 
      University of California San Diego, San Diego, CA, USA.
AD  - VA San Diego Healthcare System, San Diego, CA, USA.
FAU - Vallon, Volker
AU  - Vallon V
AD  - Division of Nephrology & Hypertension, Departments of Medicine and Pharmacology, 
      University of California San Diego, San Diego, CA, USA.
AD  - VA San Diego Healthcare System, San Diego, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170223
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Diabetic Ketoacidosis/*chemically induced
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - Ketosis/*chemically induced
MH  - *Sodium-Glucose Transporter 2 Inhibitors
OTO - NOTNLM
OT  - diabetic ketoacidosis
OT  - ketogenesis
OT  - ketone body reabsorption
OT  - ketosis
OT  - kidney
OT  - sodium glucose cotransporter
EDAT- 2017/01/19 06:00
MHDA- 2018/04/27 06:00
CRDT- 2017/01/19 06:00
PHST- 2016/10/23 00:00 [received]
PHST- 2017/01/08 00:00 [accepted]
PHST- 2017/01/19 06:00 [pubmed]
PHST- 2018/04/27 06:00 [medline]
PHST- 2017/01/19 06:00 [entrez]
AID - 10.1002/dmrr.2886 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2017 Jul;33(5). doi: 10.1002/dmrr.2886. Epub 2017 Feb 23.