Fatty Liver Is a Better Marker of Muscle Insulin Resistance than Visceral Fat Accumulation in Nonobese Japanese Men

Abstract

Metabolic diseases easily develop in non-obese Asians. We recently found that insulin resistance (IR) in muscle is closely associated with metabolic abnormalities in non-obese Japanese men and muscle IR is correlated well with both visceral fat accumulation (VFA) and fatty liver (FL). However, VFA and FL are correlated well with each other, thus it is unclear which is a better marker of muscle IR.To clarify this, we studied 87 nondiabetic non-obese middle-aged Japanese men. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity (IS) in muscle and liver. Intrahepatic lipid (IHL) and visceral fat area are measured by 1H-MRS and MRI, respectively. According to the generally accepted definition, subject was divided into 4 groups by the presence or absence of VFA (visceral fat area 100cm2) and FL (IHL 5%); control (non-VFA non-FL; n=54), VFA alone (n=18), FL alone (n=7), VFA+FL (n=8). Hepatic-IS was similar among the groups. On the other hand, muscle-IS was significantly lower in groups of FL alone and VFA+FL than the control group. Interestingly, muscle-IS of VFA alone group was comparable to the control group, and it was significantly higher than FL alone group (Figure). These differences were still significant after adjustment for confounders. These data suggested that FL is a better marker than VFA in nondiabetic non-obese men in terms of sensitivity to detect muscle IR. Disclosure S. Kadowaki: None. Y. Tamura: None. Y. Someya: None. K. Takeno: None. T. Funayama: None. Y. Furukawa: None. S. Kakehi: None. H. Kaga: None. R. Suzuki: None. D. Sugimoto: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.