Cause of Hyperglycemia in Postmenopausal Underweight Women with Impaired Glucose Tolerance
Authors: SUZUKI RURIKO , TAMURA YOSHIFUMI , SOMEYA YUKI , KAGA HIDEYOSHI , SUGIMOTO DAISUKE , KADOWAKI SATOSHI , KAKEHI SAORI , TAKENO KAGEUMI , FUNAYAMA TAKASHI , FURUKAWA YASUHIKO , SATO JUNKO , KAWAMORI RYUZO , WATADA HIROTAKA 
Published: June 2018

Japanese women have substantially lower BMI than women in other developed countries and the prevalence of underweight (BMI&lt;18.5 kg/m2) in them is currently 23.7%. Interestingly, Japanese underweight women showed ∼2 times higher risk for type 2 diabetes compared with normal weight (BMI18.5-22.9kg/m2). A previous study reported that the hyperglycemia in obese impaired glucose tolerance (IGT) subjects was primarily elicited by reduced suppression of endogenous glucose production (EGP); however, cause of hyperglycemia in underweight women with IGT has not been elucidated. To clarify the role of EGP, rate of glucose disappearance (Rd) and rate of glucose appearance of oral glucose load (Ra-Oral) on hyperglycemia in underweight women with IGT, we recruited postmenopausal underweight women with NGT (n=4) and IGT (n=9). Glucose kinetics was assessed by oral glucose tolerance test (OGTT) with double tracer (U-[13C]-glucose orally and 6,6-[2H2]-glucose intravenously). Age, BMI and percent body fat were comparable between NGT group and IGT group. IGT group showed lower area under the curve (AUC) of Rd compared with NGT group (1294±2vs. 1684±370 mg/kg fat-free mass (FFM), P&lt;0.05) during the first 2 hours of OGTT. Consistently, amount of disappeared glucose during the first 2 hours, mainly reflecting muscle glucose uptake, was 17.6g lower in IGT group compared with NGT group (39.8±9.5 vs. 57.4±14.4 g, P&lt;0.05). In contrast, AUC-EGP and AUC-Ra-Oral were comparable between the groups. AUC-insulin during OGTT was lower in IGT group compared with in NGT group (2.6±0.8 vs. 4.8±0.9 U·min/ml·103, P&lt;0.01), and it was significantly correlated to AUC-Rd (r=0.70, P&lt;0.01).
In conclusion, the present study suggested that main cause of hyperglycemia in underweight women with IGT was decreased Rd. In addition, decreased insulin secretion may partly contribute to the decreased Rd in those IGT subjects.

Disclosure
R. Suzuki: None. Y. Tamura: None. Y. Someya: None. H. Kaga: None. D. Sugimoto: None. S. Kadowaki: None. S. Kakehi: None. K. Takeno: None. T. Funayama: None. Y. Furukawa: None. J. Sato: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Novartis Pharmaceuticals Corporation, Sanofi, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd.. 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.