Chris Ho Ching Yeung1, Shiu Lun Au Yeung1, Shirley Siu Ming Fong1, C Mary Schooling2,3. 1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong SAR, China. 2. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong SAR, China. cms1@hku.hk. 3. Graduate School of Public Health and Health Policy, City University of New York, New York, USA. cms1@hku.hk.
Abstract
AIMS/HYPOTHESIS: Muscle mass and strength may protect against type 2 diabetes as a sink for glucose disposal. In randomised controlled trials, resistance training improves glucose metabolism in people with the metabolic syndrome. Whether increasing muscle mass and strength protects against diabetes in the general population is unknown. We assessed the effect of markers of muscle mass and strength on diabetes and glycaemic traits using bi-directional Mendelian randomisation. METHODS: Inverse variance weighting estimates were obtained by applying genetic variants that predict male lean mass, female lean mass and grip strength, obtained from the UK Biobank GWAS, to the largest available case-control study of diabetes (DIAbetes Genetics Replication And Meta-analysis [DIAGRAM]; n = 74,124 cases and 824,006 controls) and to a study of glycaemic traits (Meta-Analyses of Glucose and Insulin-related traits Consortium [MAGIC]). Conversely, we also applied genetic variants that predict diabetes, HbA1c, fasting glucose, fasting insulin and HOMA-B to UK Biobank summary statistics for genetic association with lean mass and grip strength. As sensitivity analyses we used weighted median, Mendelian randomisation (MR)-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and removed pleiotropic SNPs. RESULTS: Grip strength was not significantly associated with diabetes using inverse variance weighting (OR 0.72 per SD increase in grip strength, 95% CI 0.51, 1.01, p = 0.06) and including pleiotropic SNPs but was significantly associated with diabetes using MR-PRESSO (OR 0.77, 95% CI 0.62, 0.95, p = 0.02) after removing pleiotropic SNPs. Female lean mass was significantly associated with diabetes (OR 0.91, 95% CI 0.84, 0.99, p = 0.02) while male lean mass was not significant but directionally similar (OR 0.94, 95% CI 0.88, 1.01, p = 0.09). Conversely, diabetes was inversely and significantly associated with male lean mass (β -0.02 SD change in lean mass, 95% CI -0.04, -0.00, p = 0.04) and grip strength (β -0.01, 95% CI -0.02, -0.00, p = 0.01). CONCLUSIONS/ INTERPRETATION: Increased muscle mass and strength may be related to lower diabetes risk. Diabetes may also be associated with grip strength and lean mass. Muscle strength could warrant further investigation as a possible target of intervention for diabetes prevention.
AIMS/HYPOTHESIS: Muscle mass and strength may protect against type 2 diabetes as a sink for glucose disposal. In randomised controlled trials, resistance training improves glucose metabolism in people with the metabolic syndrome. Whether increasing muscle mass and strength protects against diabetes in the general population is unknown. We assessed the effect of markers of muscle mass and strength on diabetes and glycaemic traits using bi-directional Mendelian randomisation. METHODS: Inverse variance weighting estimates were obtained by applying genetic variants that predict male lean mass, female lean mass and grip strength, obtained from the UK Biobank GWAS, to the largest available case-control study of diabetes (DIAbetes Genetics Replication And Meta-analysis [DIAGRAM]; n = 74,124 cases and 824,006 controls) and to a study of glycaemic traits (Meta-Analyses of Glucose and Insulin-related traits Consortium [MAGIC]). Conversely, we also applied genetic variants that predict diabetes, HbA1c, fasting glucose, fasting insulin and HOMA-B to UK Biobank summary statistics for genetic association with lean mass and grip strength. As sensitivity analyses we used weighted median, Mendelian randomisation (MR)-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and removed pleiotropic SNPs. RESULTS: Grip strength was not significantly associated with diabetes using inverse variance weighting (OR 0.72 per SD increase in grip strength, 95% CI 0.51, 1.01, p = 0.06) and including pleiotropic SNPs but was significantly associated with diabetes using MR-PRESSO (OR 0.77, 95% CI 0.62, 0.95, p = 0.02) after removing pleiotropic SNPs. Female lean mass was significantly associated with diabetes (OR 0.91, 95% CI 0.84, 0.99, p = 0.02) while male lean mass was not significant but directionally similar (OR 0.94, 95% CI 0.88, 1.01, p = 0.09). Conversely, diabetes was inversely and significantly associated with male lean mass (β -0.02 SD change in lean mass, 95% CI -0.04, -0.00, p = 0.04) and grip strength (β -0.01, 95% CI -0.02, -0.00, p = 0.01). CONCLUSIONS/ INTERPRETATION: Increased muscle mass and strength may be related to lower diabetes risk. Diabetes may also be associated with grip strength and lean mass. Muscle strength could warrant further investigation as a possible target of intervention for diabetes prevention.
Entities:
Keywords:
Body composition; Diabetes mellitus; Grip strength; Hand strength; Lean mass; Mendelian randomisation; Muscle; Type 2 diabetes
Authors: Rita Rastogi Kalyani; Christopher D Saudek; Frederick L Brancati; Elizabeth Selvin Journal: Diabetes Care Date: 2010-02-25 Impact factor: 19.112
Authors: Robert A Scott; Vasiliki Lagou; Ryan P Welch; Eleanor Wheeler; May E Montasser; Jian'an Luan; Reedik Mägi; Rona J Strawbridge; Emil Rehnberg; Stefan Gustafsson; Stavroula Kanoni; Laura J Rasmussen-Torvik; Loïc Yengo; Cecile Lecoeur; Dmitry Shungin; Serena Sanna; Carlo Sidore; Paul C D Johnson; J Wouter Jukema; Toby Johnson; Anubha Mahajan; Niek Verweij; Gudmar Thorleifsson; Jouke-Jan Hottenga; Sonia Shah; Albert V Smith; Bengt Sennblad; Christian Gieger; Perttu Salo; Markus Perola; Nicholas J Timpson; David M Evans; Beate St Pourcain; Ying Wu; Jeanette S Andrews; Jennie Hui; Lawrence F Bielak; Wei Zhao; Momoko Horikoshi; Pau Navarro; Aaron Isaacs; Jeffrey R O'Connell; Kathleen Stirrups; Veronique Vitart; Caroline Hayward; Tõnu Esko; Evelin Mihailov; Ross M Fraser; Tove Fall; Benjamin F Voight; Soumya Raychaudhuri; Han Chen; Cecilia M Lindgren; Andrew P Morris; Nigel W Rayner; Neil Robertson; Denis Rybin; Ching-Ti Liu; Jacques S Beckmann; Sara M Willems; Peter S Chines; Anne U Jackson; Hyun Min Kang; Heather M Stringham; Kijoung Song; Toshiko Tanaka; John F Peden; Anuj Goel; Andrew A Hicks; Ping An; Martina Müller-Nurasyid; Anders Franco-Cereceda; Lasse Folkersen; Letizia Marullo; Hanneke Jansen; Albertine J Oldehinkel; Marcel Bruinenberg; James S Pankow; Kari E North; Nita G Forouhi; Ruth J F Loos; Sarah Edkins; Tibor V Varga; Göran Hallmans; Heikki Oksa; Mulas Antonella; Ramaiah Nagaraja; Stella Trompet; Ian Ford; Stephan J L Bakker; Augustine Kong; Meena Kumari; Bruna Gigante; Christian Herder; Patricia B Munroe; Mark Caulfield; Jula Antti; Massimo Mangino; Kerrin Small; Iva Miljkovic; Yongmei Liu; Mustafa Atalay; Wieland Kiess; Alan L James; Fernando Rivadeneira; Andre G Uitterlinden; Colin N A Palmer; Alex S F Doney; Gonneke Willemsen; Johannes H Smit; Susan Campbell; Ozren Polasek; Lori L Bonnycastle; Serge Hercberg; Maria Dimitriou; Jennifer L Bolton; Gerard R Fowkes; Peter Kovacs; Jaana Lindström; Tatijana Zemunik; Stefania Bandinelli; Sarah H Wild; Hanneke V Basart; Wolfgang Rathmann; Harald Grallert; Winfried Maerz; Marcus E Kleber; Bernhard O Boehm; Annette Peters; Peter P Pramstaller; Michael A Province; Ingrid B Borecki; Nicholas D Hastie; Igor Rudan; Harry Campbell; Hugh Watkins; Martin Farrall; Michael Stumvoll; Luigi Ferrucci; Dawn M Waterworth; Richard N Bergman; Francis S Collins; Jaakko Tuomilehto; Richard M Watanabe; Eco J C de Geus; Brenda W Penninx; Albert Hofman; Ben A Oostra; Bruce M Psaty; Peter Vollenweider; James F Wilson; Alan F Wright; G Kees Hovingh; Andres Metspalu; Matti Uusitupa; Patrik K E Magnusson; Kirsten O Kyvik; Jaakko Kaprio; Jackie F Price; George V Dedoussis; Panos Deloukas; Pierre Meneton; Lars Lind; Michael Boehnke; Alan R Shuldiner; Cornelia M van Duijn; Andrew D Morris; Anke Toenjes; Patricia A Peyser; John P Beilby; Antje Körner; Johanna Kuusisto; Markku Laakso; Stefan R Bornstein; Peter E H Schwarz; Timo A Lakka; Rainer Rauramaa; Linda S Adair; George Davey Smith; Tim D Spector; Thomas Illig; Ulf de Faire; Anders Hamsten; Vilmundur Gudnason; Mika Kivimaki; Aroon Hingorani; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Dorret I Boomsma; Kari Stefansson; Pim van der Harst; Josée Dupuis; Nancy L Pedersen; Naveed Sattar; Tamara B Harris; Francesco Cucca; Samuli Ripatti; Veikko Salomaa; Karen L Mohlke; Beverley Balkau; Philippe Froguel; Anneli Pouta; Marjo-Riitta Jarvelin; Nicholas J Wareham; Nabila Bouatia-Naji; Mark I McCarthy; Paul W Franks; James B Meigs; Tanya M Teslovich; Jose C Florez; Claudia Langenberg; Erik Ingelsson; Inga Prokopenko; Inês Barroso Journal: Nat Genet Date: 2012-08-12 Impact factor: 38.330
Authors: Josée Dupuis; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Nicole Soranzo; Anne U Jackson; Eleanor Wheeler; Nicole L Glazer; Nabila Bouatia-Naji; Anna L Gloyn; Cecilia M Lindgren; Reedik Mägi; Andrew P Morris; Joshua Randall; Toby Johnson; Paul Elliott; Denis Rybin; Gudmar Thorleifsson; Valgerdur Steinthorsdottir; Peter Henneman; Harald Grallert; Abbas Dehghan; Jouke Jan Hottenga; Christopher S Franklin; Pau Navarro; Kijoung Song; Anuj Goel; John R B Perry; Josephine M Egan; Taina Lajunen; Niels Grarup; Thomas Sparsø; Alex Doney; Benjamin F Voight; Heather M Stringham; Man Li; Stavroula Kanoni; Peter Shrader; Christine Cavalcanti-Proença; Meena Kumari; Lu Qi; Nicholas J Timpson; Christian Gieger; Carina Zabena; Ghislain Rocheleau; Erik Ingelsson; Ping An; Jeffrey O'Connell; Jian'an Luan; Amanda Elliott; Steven A McCarroll; Felicity Payne; Rosa Maria Roccasecca; François Pattou; Praveen Sethupathy; Kristin Ardlie; Yavuz Ariyurek; Beverley Balkau; Philip Barter; John P Beilby; Yoav Ben-Shlomo; Rafn Benediktsson; Amanda J Bennett; Sven Bergmann; Murielle Bochud; Eric Boerwinkle; Amélie Bonnefond; Lori L Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Suzannah J Bumpstead; Guillaume Charpentier; Yii-Der Ida Chen; Peter Chines; Robert Clarke; Lachlan J M Coin; Matthew N Cooper; Marilyn Cornelis; Gabe Crawford; Laura Crisponi; Ian N M Day; Eco J C de Geus; Jerome Delplanque; Christian Dina; Michael R Erdos; Annette C Fedson; Antje Fischer-Rosinsky; Nita G Forouhi; Caroline S Fox; Rune Frants; Maria Grazia Franzosi; Pilar Galan; Mark O Goodarzi; Jürgen Graessler; Christopher J Groves; Scott Grundy; Rhian Gwilliam; Ulf Gyllensten; Samy Hadjadj; Göran Hallmans; Naomi Hammond; Xijing Han; Anna-Liisa Hartikainen; Neelam Hassanali; Caroline Hayward; Simon C Heath; Serge Hercberg; Christian Herder; Andrew A Hicks; David R Hillman; Aroon D Hingorani; Albert Hofman; Jennie Hui; Joe Hung; Bo Isomaa; Paul R V Johnson; Torben Jørgensen; Antti Jula; Marika Kaakinen; Jaakko Kaprio; Y Antero Kesaniemi; Mika Kivimaki; Beatrice Knight; Seppo Koskinen; Peter Kovacs; Kirsten Ohm Kyvik; G Mark Lathrop; Debbie A Lawlor; Olivier Le Bacquer; Cécile Lecoeur; Yun Li; Valeriya Lyssenko; Robert Mahley; Massimo Mangino; Alisa K Manning; María Teresa Martínez-Larrad; Jarred B McAteer; Laura J McCulloch; Ruth McPherson; Christa Meisinger; David Melzer; David Meyre; Braxton D Mitchell; Mario A Morken; Sutapa Mukherjee; Silvia Naitza; Narisu Narisu; Matthew J Neville; Ben A Oostra; Marco Orrù; Ruth Pakyz; Colin N A Palmer; Giuseppe Paolisso; Cristian Pattaro; Daniel Pearson; John F Peden; Nancy L Pedersen; Markus Perola; Andreas F H Pfeiffer; Irene Pichler; Ozren Polasek; Danielle Posthuma; Simon C Potter; Anneli Pouta; Michael A Province; Bruce M Psaty; Wolfgang Rathmann; Nigel W Rayner; Kenneth Rice; Samuli Ripatti; Fernando Rivadeneira; Michael Roden; Olov Rolandsson; Annelli Sandbaek; Manjinder Sandhu; Serena Sanna; Avan Aihie Sayer; Paul Scheet; Laura J Scott; Udo Seedorf; Stephen J Sharp; Beverley Shields; Gunnar Sigurethsson; Eric J G Sijbrands; Angela Silveira; Laila Simpson; Andrew Singleton; Nicholas L Smith; Ulla Sovio; Amy Swift; Holly Syddall; Ann-Christine Syvänen; Toshiko Tanaka; Barbara Thorand; Jean Tichet; Anke Tönjes; Tiinamaija Tuomi; André G Uitterlinden; Ko Willems van Dijk; Mandy van Hoek; Dhiraj Varma; Sophie Visvikis-Siest; Veronique Vitart; Nicole Vogelzangs; Gérard Waeber; Peter J Wagner; Andrew Walley; G Bragi Walters; Kim L Ward; Hugh Watkins; Michael N Weedon; Sarah H Wild; Gonneke Willemsen; Jaqueline C M Witteman; John W G Yarnell; Eleftheria Zeggini; Diana Zelenika; Björn Zethelius; Guangju Zhai; Jing Hua Zhao; M Carola Zillikens; Ingrid B Borecki; Ruth J F Loos; Pierre Meneton; Patrik K E Magnusson; David M Nathan; Gordon H Williams; Andrew T Hattersley; Kaisa Silander; Veikko Salomaa; George Davey Smith; Stefan R Bornstein; Peter Schwarz; Joachim Spranger; Fredrik Karpe; Alan R Shuldiner; Cyrus Cooper; George V Dedoussis; Manuel Serrano-Ríos; Andrew D Morris; Lars Lind; Lyle J Palmer; Frank B Hu; Paul W Franks; Shah Ebrahim; Michael Marmot; W H Linda Kao; James S Pankow; Michael J Sampson; Johanna Kuusisto; Markku Laakso; Torben Hansen; Oluf Pedersen; Peter Paul Pramstaller; H Erich Wichmann; Thomas Illig; Igor Rudan; Alan F Wright; Michael Stumvoll; Harry Campbell; James F Wilson; Richard N Bergman; Thomas A Buchanan; Francis S Collins; Karen L Mohlke; Jaakko Tuomilehto; Timo T Valle; David Altshuler; Jerome I Rotter; David S Siscovick; Brenda W J H Penninx; Dorret I Boomsma; Panos Deloukas; Timothy D Spector; Timothy M Frayling; Luigi Ferrucci; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson; Cornelia M van Duijn; Yurii S Aulchenko; Antonio Cao; Angelo Scuteri; David Schlessinger; Manuela Uda; Aimo Ruokonen; Marjo-Riitta Jarvelin; Dawn M Waterworth; Peter Vollenweider; Leena Peltonen; Vincent Mooser; Goncalo R Abecasis; Nicholas J Wareham; Robert Sladek; Philippe Froguel; Richard M Watanabe; James B Meigs; Leif Groop; Michael Boehnke; Mark I McCarthy; Jose C Florez; Inês Barroso Journal: Nat Genet Date: 2010-01-17 Impact factor: 38.330
Authors: Jack Bowden; Fabiola Del Greco M; Cosetta Minelli; George Davey Smith; Nuala A Sheehan; John R Thompson Journal: Int J Epidemiol Date: 2016-12-01 Impact factor: 7.196
Authors: Stamatina Iliodromiti; James McLaren; Nazim Ghouri; Melissa R Miller; Olof Dahlqvist Leinhard; Jennifer Linge; Stuart Ballantyne; Jonathan Platt; John Foster; Scott Hanvey; Unjali P Gujral; Alka Kanaya; Naveed Sattar; Mary Ann Lumsden; Jason M R Gill Journal: Diabetologia Date: 2022-10-13 Impact factor: 10.460
Authors: Junxi Liu; Shiu Lun Au Yeung; Baoting He; Man Ki Kwok; Gabriel Matthew Leung; C Mary Schooling Journal: PLoS One Date: 2019-09-10 Impact factor: 3.240
Authors: Junxi Liu; Shiu Lun Au Yeung; Man Ki Kwok; June Yue Yan Leung; Lai Ling Hui; Gabriel Matthew Leung; C Mary Schooling Journal: PLoS One Date: 2020-02-11 Impact factor: 3.240
Authors: Xue Liang; Chao Qiang Jiang; Wei Sen Zhang; Feng Zhu; Ya Li Jin; Kar Keung Cheng; Tai Hing Lam; Lin Xu Journal: BMC Geriatr Date: 2020-10-12 Impact factor: 3.921