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Dorte Glintborg Department of Endocrinology, Odense University Hospital, Odense, Denmark
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Katrine Hass Rubin Open Patient Data Explorative Network, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark

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Simon Bang Mohr Kristensen Open Patient Data Explorative Network, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark

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Øjvind Lidegaard Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Guy T’Sjoen Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Gent, Belgium

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Aisa Burgwal Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Gent, Belgium

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Malene Hilden Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Centre for Gender Identity, Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Marianne Skovsager Andersen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

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Jokela M Avendaño M Muennig P Guida F Ricceri F d’Errico A Barros H Bochud M Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women

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Adriana J van Ballegooijen Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Marjolein Visser Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Marieke B Snijder Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Jacqueline M Dekker Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Giel Nijpels Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Coen D A Stehouwer Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Michaela Diamant Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Ingeborg A Brouwer Department of Health Sciences, Department of Epidemiology and Biostatistics, Department of Public Health, Department of General Practice, Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Faculty of Earth and Life Sciences, EMGO Institute for Health and Care Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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.412 Type 2 diabetes (%) 28.9 18.9 22.2 17.4 0.051 21.4 19.8 16.2 30.6 0.039 Arterial hypertension (%) 77.3 77.6 63.0 58.3 0.001 56.6 65.1 72.9 82.1 <0.001 Lifestyle  Cigarette smokers (%) 16.7 17.6 9.4 20.0 0.122 20.5 15.2 15.5 12.3 0.365  Physical activity

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Angelica Amorim Amato Department of Pharmaceutical Sciences, University of Brasilia, Brasilia, Brazil
Department of Developmental and Cell Biology, University of California, Irvine, California, USA

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Hailey Brit Wheeler Department of Developmental and Cell Biology, University of California, Irvine, California, USA

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Bruce Blumberg Department of Developmental and Cell Biology, University of California, Irvine, California, USA
Department of Pharmaceutical Sciences, University of California, Irvine, California, USA
Department of Biomedical Engineering, University of California, Irvine, California, USA

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complex ‘environmental factors’ (broadly defined). These can include socio-economic status, family lifestyle, workplace culture, and urban design (the ‘built environment’). Coupled with inadequate physical activity and nutritional imbalance, these may

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Jun-Xin Yan The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China

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Bin-Jing Pan The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China

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Ping-Ping Zhao The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China

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Li-Ting Wang The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

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Jing-Fang Liu The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

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Song-Bo Fu The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

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, this results in an accumulation of free fatty acids (FFAs) inside the liver (FFA), which aggravates insulin resistance by inhibiting insulin receptor signaling pathway. Finally, genetic and epidemiological factors, including diet, lifestyle

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Yaqian Mao Shengli Clinical Medical College of Fujian Medical University, Fujian, China
Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Lizhen Xu Shengli Clinical Medical College of Fujian Medical University, Fujian, China

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Ting Xue Shengli Clinical Medical College of Fujian Medical University, Fujian, China

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Jixing Liang Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Wei Lin Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Junping Wen Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Huibin Huang Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Liantao Li Department of Endocrinology, Fujian Provincial Hospital, Fujian, China

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Gang Chen Shengli Clinical Medical College of Fujian Medical University, Fujian, China
Department of Endocrinology, Fujian Provincial Hospital, Fujian, China
Fujian Provincial Key Laboratory of Medical Analysis, Fujian Academy of Medical, Fujian, China

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, auxiliary examinations, co-morbidities, and lifestyles. We selected 10 characteristic variables with nonzero coefficients from 44 variables through the LASSO regression model, including age, neck circumference, waist-to-height ratio, BMI, TG, IFG

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Siphiwe N Dlamini SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU), School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Non-communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa

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Zané Lombard Division of Human Genetics, National Health Laboratory Service, and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Lisa K Micklesfield SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU), School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Nigel Crowther Department of Chemical Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Shane A Norris SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU), School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Tracy Snyman Department of Chemical Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Andrew A Crawford Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK

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Brian R Walker BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
Institute of Genetic Medicine to Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

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Julia H Goedecke SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU), School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Non-communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa

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study. Details of data collection protocols for the AWI-Gen study have been described elsewhere ( 24 ). Study sample 2 included participants (501 men and 529 women) recruited as part of a longitudinal study designed to identify the determinants of type 2

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David S Mathiesen Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Jonatan I Bagger Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Katrine B Hansen Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark

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Anders E Junker Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Astrid Plamboeck Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Signe Harring Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark

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Thomas Idorn Center for Cancer and Organ Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Mads Hornum Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Cancer and Organ Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Jens J Holst Novartis Healthcare A/S, Copenhagen, Denmark

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Anna E Jonsson Novartis Healthcare A/S, Copenhagen, Denmark

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Torben Hansen Novartis Healthcare A/S, Copenhagen, Denmark

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Tina Vilsbøll Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Novartis Healthcare A/S, Copenhagen, Denmark
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Asger Lund Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Novartis Healthcare A/S, Copenhagen, Denmark
Department of Nephrology, Rigshospitalet, 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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Introduction Type 2 diabetes is a multifactorial disorder with environmental triggers such as a sedentary lifestyle, physical inactivity and ensuing overweight. Genetic predisposition also plays an important role in the development of the

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Chengnan Guo Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yixi Xu Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yange Ma Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Xin Xu Wenzhou Medical University, Wenzhou, Zhejiang, China

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Fang Peng Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Hui-hui Li Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Dongzhen Jin Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Shu-zhen Zhao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Zhezheng Xia Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Mengyuan Lai Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Mingzhu Che Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Ruogu Huang Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Yanan Wang Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China

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Depeng Jiang Department of Community Health Sciences, College of Medicine, University of Manitoba, Winnipeg, Canada

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Chao Zheng The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Guangyun Mao Division of Epidemiology and Health Statistics, Department of Preventive Medicine, School of Public Health & Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China

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important chronic non-communicable disease, the likelihood of developing DR would be affected by a lot of factors including dyslipidemia, hypertension, metabolic syndrome, lifestyle and others. All these known or unknown confounders would modify the results

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Mirjam M Oosterwerff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Rosa Meijnen Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Natasja M Van Schoor Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Dirk L Knol Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mark H H Kramer Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Mireille N M Van Poppel Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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Paul Lips Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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E Marelise W Eekhoff Departments of Internal Medicine, Epidemiology and Biostatistics, Public and Occupational Health, Endocrine Section

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physical activity guidelines, a lifestyle intervention could be essential for the health of overweight non-western immigrants. When 25(OH)D concentrations were >60 nmol/l after intervention, there was borderline improvement of physical exercise capacity in

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Luca Boeri Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Paolo Capogrosso Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Walter Cazzaniga Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Edoardo Pozzi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Luigi Candela Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Federico Belladelli Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Davide Oreggia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Eugenio Ventimiglia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Nicolò Schifano Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Giuseppe Fallara Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Marina Pontillo Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan, Italy

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Costantino Abbate Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Emanuele Montanari Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Francesco Montorsi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Andrea Salonia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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). Of relevance, SHBG was found to linearly increase with ageing while decreasing with increasing BMI values ( 8 , 9 , 11 ). Additionally, SHBG per se has also been shown to be an independent determinant of DM, metabolic syndrome (MetS

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