Visceral Adiposity and Diabetes: Translating Form to Function Using Imaging

Summary

This study is a clinical study to investigate the gluconeogenesis pathway related to visceral adipose tissue (VAT) in obese individuals without type 2 diabetes and the effects of empagliflozin (EMPA) on glucose homeostasis in viscerally-obese individuals using functional studies of glycerol metabolism in hepatic gluconeogenesis using a well-validated nuclear magnetic resonance (NMR) spectroscopy platform.

Timeline

Start

2016-03

Primary completion

2018-01

Completion

2018-11

Outcome

Met primary endpoint

paper Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). PMID 32568464 ↗

Publications

• Background Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity (Silver Spring). 2013 Sep;21(9):E439-47. doi: 10.1002/oby.20135. Epub 2013 May 19.
• Background Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012 Sep 19;308(11):1150-9. doi: 10.1001/2012.jama.11132.
• Background Nurjhan N, Kennedy F, Consoli A, Martin C, Miles J, Gerich J. Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo. Metabolism. 1988 Apr;37(4):386-9. doi: 10.1016/0026-0495(88)90140-0.
• Background Baba H, Zhang XJ, Wolfe RR. Glycerol gluconeogenesis in fasting humans. Nutrition. 1995 Mar-Apr;11(2):149-53.
• Background Jin ES, Sherry AD, Malloy CR. Interaction between the pentose phosphate pathway and gluconeogenesis from glycerol in the liver. J Biol Chem. 2014 Nov 21;289(47):32593-603. doi: 10.1074/jbc.M114.577692. Epub 2014 Oct 6.
• Neeland IJ, de Albuquerque Rocha N, Hughes C, Ayers CR, Malloy CR, Jin ES. Effects of Empagliflozin Treatment on Glycerol-Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial. Obesity (Silver Spring). 2020 Jul;28(7):1254-1262. doi: 10.1002/oby.22854.

Drugs

Indications