Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients

Diabetes, Obesity and Metabolism

Volumn 19, Issue 6, 2017, Pages 809-813

  Al Jobori, Hussein ^a   Daniele, Giuseppe ^a   Adams, John ^a   Cersosimo, Eugenio ^a   Triplitt, Curtis ^a   DeFronzo, Ralph A ^a   Abdul Ghani, Muhammad ^a  

^a Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

empagliflozin; fasting plasma glucose; free fatty acid; glucagon; insulin; ketone; SGLT2 inhibitor

Indexed keywords

EMPAGLIFLOZIN; FATTY ACID; GLUCAGON; GLUCOSE; INSULIN; KETONE; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE; SODIUM GLUCOSE COTRANSPORTER 2;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DIAGNOSTIC TEST ACCURACY STUDY; DIET RESTRICTION; FEMALE; GLUCAGON BLOOD LEVEL; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; HUMAN; INSULIN BLOOD LEVEL; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PREDICTION; SENSITIVITY AND SPECIFICITY; ANTAGONISTS AND INHIBITORS; BLOOD; DRUG EFFECTS; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; MIDDLE AGED;

BENZHYDRYL COMPOUNDS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; FASTING; FATTY ACIDS, NONESTERIFIED; FEMALE; GLUCAGON; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; KETONES; MALE; MIDDLE AGED; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 85017129461     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12881     Document Type: Article

References (16)

1. Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011;32:515-531.
2. Monica Reddy RP, Inzucchi SE. SGLT2 inhibitors in the management of type 2 diabetes. Endocrine. 2016;53:364-372.
3. Modi A, Agrawal A, Morgan F. Euglycemic diabetic ketoacidosis. Curr Diabetes Rev. 2016. [Epub ahead of print].
4. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1687-1693.
5. Peters AL, Henry RR, Thakkar P, Tong C, Alba M. Diabetic ketoacidosis with canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 1 diabetes. Diabetes Care. 2016;39:532-538.
6. DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol. 2017;13:11-26.
7. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances glucose production. J Clin Invest. 2014;124:509-514.
8. Merovci A, Abdul-Ghani M, Mari A, et al. Dapagliflozin lowers plasma glucose concentration and improves beta cell function. J Clin Endocrinol Metab. 2015;100:1927-1932.
9. Ferrannini E, Baldi S, Frascerra S, et al. Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes. 2016;65:1190-1195.
10. Daniele G, Xiong J, Solis-Herrera C, et al. Dapagliflozin enhances fat oxidation and ketone production in patients with Type 2 diabetes. Diabetes Care. 2016;39:2036-2041.
11. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124:499-508.
12. Abdul-Ghani MA, DeFronzo RA, Norton L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans. Diabetes. 2013;62:3324-3328.
13. Komoroski B, Vachharajani N, Boulton D, et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther. 2009;85:520-526.
14. Alatrach M, Agyin C, Adams J, DeFronzo RA, Abdul-Ghani M. Decreased basal hepatic glucose uptake in subjects with impaired fasting glucose. Diabetologia. 2016;39:2036-2041.
15. Bonner C, Kerr-Conte J, Gmyr V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512-517.
16. Groop LC, Bonadonna RC, Del Prato S, et al. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest. 1989;84:205-213.