The Shape of the Glucose Response Curve during an Oral Glucose Tolerance Test Was Associated with Muscle Insulin Sensitivity and Visceral Fat Accumulation in Nonobese Healthy Men

Previous studies reported that the shape of glucose response curve during an oral glucose tolerance test (OGTT) could be a marker of insulin sensitivity in obese subjects. The biphasic response curve was defined by a second rise in glucose concentration of >4.5mg/dl after the decline in glucose during OGTT and subjects with biphasic response curve were insulin sensitive and had low risk of type 2 diabetes compared with subjects with monophasic response curve. While type 2 diabetes is often developed in non-obese Asians, it is still unclear whether the subjects with biphasic response curve are also insulin sensitive in non-obese healthy men. To clarify this, we studied 49 non-obese (BMI<25 kg/m2) healthy Japanese men. We evaluated insulin sensitivity in muscle and liver by 2-step hyperinsulinemic euglycemic clamp. We also measured ectopic fat in muscle and liver and subcutaneous and viscera fat areas by 1H-MRS and MRI, respectively. Based on the shape of glucose response curve during OGTT, we divided the subjects into monophasic (n=31) and biphasic group (n=18). The 60- and 90-min glucose levels were significantly lower in biphasic group than monophasic group (60-min:157.5±30.9 vs. 126.4±31.3mg/dl, p<0.01, 90-min:123.4±23.4 vs. 103.8±20.6mg/dl, p<0.01), while glucose levels at other time points and insulinogenic index were comparable between the groups. In addition, biphasic group showed lower visceral fat area (82.7±27.8 vs. 62.6±24.2 cm2, P=0.014) and higher muscle insulin sensitivity (0.22±0.vs. 0.27±0.09 mg/kg FFM·min-1 ·μU-1·ml, P<0.020) compared with monophasic group. Ectopic fat accumulation in muscle and liver, subcutaneous fat area and hepatic insulin sensitivity were comparable between the groups. In conclusion, biphasic glucose response curve is a marker of elevated muscle insulin sensitivity with less visceral fat in non-obese Japanese healthy men. Disclosure H. Kaga: None. Y. Tamura: None. K. Takeno: None. S. Kakehi: None. Y. Someya: None. R. Suzuki: None. S. Kadowaki: None. D. Sugimoto: None. Y. Furukawa: None. T. Funayama: 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.