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Melony C Fortuin-de Smidt Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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Amy E Mendham Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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Jon Hauksson Department of Radiation Sciences, Radiation Physics and Biomedical Engineering, Umea University, Umea, Sweden

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Ali Alhamud Department of Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa
The Modern Pioneer Center and ArSMRM for MRI Training and Development, Tripoli, Libya

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Darko Stefanovski Department of Clinical Studies, New Bolton Centre, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA

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Olah Hakim Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Jeroen Swart Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa

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Louise M Goff Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Steven E Kahn Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington, USA

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Tommy Olsson Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden

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Julia H Goedecke Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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Introduction The acute insulin response (AIRg) relative to the prevailing level of insulin sensitivity (S I ) described by the disposition index (DI) estimates the β-cell function, which is a key component in the pathogenesis of type 2

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Shenglong Le Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Leiting Xu Medical School, Ningbo University, Ningbo, China

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Moritz Schumann Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Na Wu Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Timo Törmäkangas Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Markku Alén Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland

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Sulin Cheng Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Petri Wiklund Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Department of Epidemiology and Biostatistics, Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland

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with idiopathic hypoandrogenism and in precocious pubertal girls treated with gonadotropin-releasing hormone analogs ( 4 , 5 ). Some of the variation in circulating SHBG might be related to body composition and insulin sensitivity, both of which change

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Qing Zhou Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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Li Yong Zhang Department of Thyroid Surgery, Minimal Invasive Center, Fujian Medical University Union Hospital, Fuzhou, China

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Mei Feng Dai Department of Clinical Lab, Fujian Maternity and Child Health Hospital, Fuzhou, China

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Zhen Li Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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Chao Chun Zou Department of Endocrinology, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

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Hui Liu Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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hypothyroidism have a high risk for insulin resistance-associated disorders, such as metabolic syndrome and cardiovascular disease ( 1 , 2 ). Moreover, independent of other variables, a significant positive association exists between TSH levels and insulin

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Kristin Ottarsdottir Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Margareta Hellgren Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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David Bock Biostatistics, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Anna G Nilsson Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Bledar Daka Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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different cohorts including men and women, respectively, suggesting a causal effect. The mechanism behind the association between SHGB and type 2 diabetes is not fully understood, but may be mediated through insulin resistance ( 5 ). In a meta

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Sandra Pereira Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Jessy Moore Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada

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Jia-Xu Li Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada

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Wen Qin Yu Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Husam Ghanim Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo, Kaleida Health, Buffalo, New York, USA

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Filip Vlavcheski Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada

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Yemisi Deborah Joseph Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Paresh Dandona Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo, Kaleida Health, Buffalo, New York, USA

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Allen Volchuk Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

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Carolyn L Cummins Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada

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Evangelia Tsiani Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada

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Adria Giacca Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada

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Introduction Obesity is characterized by elevated circulating free fatty acids (FFAs) that cause insulin resistance in the liver and periphery ( 1 , 2 ). FFAs induce endoplasmic reticulum (ER) stress, which occurs when misfolded or unfolded

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Kristin Ottarsdottir Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Anna G Nilsson Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Margareta Hellgren Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Ulf Lindblad Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Bledar Daka Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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cytokines, leptin, estradiol and insulin. These substances may inhibit the activity of the hypothalamic–pituitary gonadal axis at multiple levels, thus lowering the concentrations of testosterone ( 7 ). There is also evidence that obesity increases aromatase

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Selina Mäkinen Minerva Foundation Institute for Medical Research, Helsinki, Finland
University of Helsinki, Department of Medicine, and Abdominal Center, Endocrinology, Helsinki University Central Hospital, Helsinki, Finland

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Yen H Nguyen Minerva Foundation Institute for Medical Research, Helsinki, Finland
University of Helsinki, Department of Medicine, and Abdominal Center, Endocrinology, Helsinki University Central Hospital, Helsinki, Finland

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Paulina Skrobuk Minerva Foundation Institute for Medical Research, Helsinki, Finland
University of Helsinki, Department of Medicine, and Abdominal Center, Endocrinology, Helsinki University Central Hospital, Helsinki, Finland

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Heikki A Koistinen Minerva Foundation Institute for Medical Research, Helsinki, Finland
University of Helsinki, Department of Medicine, and Abdominal Center, Endocrinology, Helsinki University Central Hospital, Helsinki, Finland

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Introduction Excess dietary fat and sedentary lifestyle predispose to insulin resistance and type 2 diabetes. As skeletal muscle accounts for 80% of glucose disposal under insulin-stimulated conditions ( 1 , 2 ), it is an important target

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Marie Reeberg Sass Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nicolai Jacob Wewer Albrechtsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

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Jens Pedersen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Endocrinology and Nephrology, Nordsjællands University Hospital, Hillerød, Denmark

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Kristine Juul Hare Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nis Borbye-Lorenzen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark

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Katalin Kiss Department of Pathology, Rigshospitalet, Copenhagen, Denmark

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Tina Vilsbøll Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Filip Krag Knop Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Steen Seier Poulsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Niklas Rye Jørgensen Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens Juul Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Cathrine Ørskov Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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-acting somatostatin analogue, which inhibits the secretion of the gastrointestinal hormones) significantly blunted the suppression of bone resorption after oral glucose in a study by Clowes et al . ( 5 ). However, in the same study, insulin was also inhibited by the

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Anna Kistner Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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Mireille Vanpée Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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Kerstin Hall Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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(defined as birth weight (BW) below 2500 g) has been proposed to lead to insulin resistance and type 2 diabetes (1, 2, 3, 4) . In studies of individuals born SGA at term (defined as BW SDS below −2 SDS), signs of insulin resistance have been detected in

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Yuka Goto Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Yoshie Otsuka Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Kenji Ashida Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Ayako Nagayama Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Nao Hasuzawa Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Shimpei Iwata Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Kento Hara Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Munehisa Tsuruta Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Nobuhiko Wada Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Seiichi Motomura Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan
Division of Endocrinology and Metabolism, Diabetes Center, Kurume Medical Center, Kokubu-machi, Kurume-city, Fukuoka, Japan

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Yuji Tajiri Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan
Division of Endocrinology and Metabolism, Diabetes Center, Kurume Medical Center, Kokubu-machi, Kurume-city, Fukuoka, Japan

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Masatoshi Nomura Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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the risk of cardiovascular events and mortality in diabetes mellitus ( 1 , 2 ). SGLT2 inhibitors exert glucose-lowering effects, improving insulin sensitivity through the changes in the body composition over long-term treatment ( 3 , 4 ). While

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