Aaron Jesuthasan1, Sviatlana Zhyzhneuskaya1, Carl Peters1, Alison C Barnes2, Kieren G Hollingsworth1, Naveed Sattar3, Michael E J Lean4, Roy Taylor5, Ahmad H Al-Mrabeh6,7. 1. Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. 2. Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK. 3. Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK. 4. School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK. 5. Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. roy.taylor@newcastle.ac.uk. 6. Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. ahmad.al-mrabeh@ed.ac.uk. 7. Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK. ahmad.al-mrabeh@ed.ac.uk.
Abstract
AIMS/HYPOTHESIS: Type 2 diabetes confers a greater relative increase in CVD risk in women compared with men. We examined sex differences in intraorgan fat and hepatic VLDL1-triacylglycerol (VLDL1-TG) export before and after major dietary weight loss. METHODS: A group with type 2 diabetes (n = 64, 30 male/34 female) and a group of healthy individuals (n = 25, 13 male/12 female) were studied. Intraorgan and visceral fat were quantified by magnetic resonance and VLDL1-TG export by intralipid infusion techniques. RESULTS: Triacylglycerol content of the liver and pancreas was elevated in people with diabetes with no sex differences (liver 16.4% [9.3-25.0%] in women vs 11.9% [7.0-23.1%] in men, p = 0.57, and pancreas 8.3 ± 0.5% vs 8.5 ± 0.4%, p = 0.83, respectively). In the absence of diabetes, fat levels in both organs were lower in women than men (1.0% [0.9-1.7%] vs 4.5% [1.9-8.0%], p = 0.005, and 4.7 ± 0.4% vs 7.6 ± 0.5%, p< 0.0001, respectively). Women with diabetes had higher hepatic VLDL1-TG production rate and plasma VLDL1-TG than healthy women (559.3 ± 32.9 vs 403.2 ± 45.7 mg kg-1 day-1, p = 0.01, and 0.45 [0.26-0.77] vs 0.25 [0.13-0.33] mmol/l, p = 0.02), whereas there were no differences in men (548.8 ± 39.8 vs 506.7 ± 29.2 mg kg-1 day-1, p = 0.34, and 0.72 [0.53-1.15] vs 0.50 [0.32-0.68] mmol/l, p = 0.26). Weight loss decreased intraorgan fat and VLDL1-TG production rates regardless of sex, and these changes were accompanied by similar rates of diabetes remission (65.4% vs 71.0%) and CVD risk reduction (59.8% vs 41.5%) in women and men, respectively. CONCLUSIONS/ INTERPRETATION: In type 2 diabetes, women have liver and pancreas fat levels as high as those of men, associated with raised hepatic VLDL1-TG production rates. Dynamics of triacylglycerol turnover differ between sexes in type 2 diabetes and following weight loss. These changes may contribute to the disproportionately raised cardiovascular risk of women with diabetes.
AIMS/HYPOTHESIS: Type 2 diabetes confers a greater relative increase in CVD risk in women compared with men. We examined sex differences in intraorgan fat and hepatic VLDL1-triacylglycerol (VLDL1-TG) export before and after major dietary weight loss. METHODS: A group with type 2 diabetes (n = 64, 30 male/34 female) and a group of healthy individuals (n = 25, 13 male/12 female) were studied. Intraorgan and visceral fat were quantified by magnetic resonance and VLDL1-TG export by intralipid infusion techniques. RESULTS: Triacylglycerol content of the liver and pancreas was elevated in people with diabetes with no sex differences (liver 16.4% [9.3-25.0%] in women vs 11.9% [7.0-23.1%] in men, p = 0.57, and pancreas 8.3 ± 0.5% vs 8.5 ± 0.4%, p = 0.83, respectively). In the absence of diabetes, fat levels in both organs were lower in women than men (1.0% [0.9-1.7%] vs 4.5% [1.9-8.0%], p = 0.005, and 4.7 ± 0.4% vs 7.6 ± 0.5%, p< 0.0001, respectively). Women with diabetes had higher hepatic VLDL1-TG production rate and plasma VLDL1-TG than healthy women (559.3 ± 32.9 vs 403.2 ± 45.7 mg kg-1 day-1, p = 0.01, and 0.45 [0.26-0.77] vs 0.25 [0.13-0.33] mmol/l, p = 0.02), whereas there were no differences in men (548.8 ± 39.8 vs 506.7 ± 29.2 mg kg-1 day-1, p = 0.34, and 0.72 [0.53-1.15] vs 0.50 [0.32-0.68] mmol/l, p = 0.26). Weight loss decreased intraorgan fat and VLDL1-TG production rates regardless of sex, and these changes were accompanied by similar rates of diabetes remission (65.4% vs 71.0%) and CVD risk reduction (59.8% vs 41.5%) in women and men, respectively. CONCLUSIONS/ INTERPRETATION: In type 2 diabetes, women have liver and pancreas fat levels as high as those of men, associated with raised hepatic VLDL1-TG production rates. Dynamics of triacylglycerol turnover differ between sexes in type 2 diabetes and following weight loss. These changes may contribute to the disproportionately raised cardiovascular risk of women with diabetes.
Authors: Yingjie Ji; Andrianos M Yiorkas; Francesca Frau; Dennis Mook-Kanamori; Harald Staiger; E Louise Thomas; Naeimeh Atabaki-Pasdar; Archie Campbell; Jessica Tyrrell; Samuel E Jones; Robin N Beaumont; Andrew R Wood; Marcus A Tuke; Katherine S Ruth; Anubha Mahajan; Anna Murray; Rachel M Freathy; Michael N Weedon; Andrew T Hattersley; Caroline Hayward; Jürgen Machann; Hans-Ulrich Häring; Paul Franks; Renée de Mutsert; Ewan Pearson; Norbert Stefan; Timothy M Frayling; Karla V Allebrandt; Jimmy D Bell; Alexandra I Blakemore; Hanieh Yaghootkar Journal: Diabetes Date: 2018-10-23 Impact factor: 9.461
Authors: Ahmad Al-Mrabeh; Sviatlana V Zhyzhneuskaya; Carl Peters; Alison C Barnes; Shaden Melhem; Aaron Jesuthasan; Benjamin Aribisala; Kieren G Hollingsworth; Georg Lietz; John C Mathers; Naveed Sattar; Michael E J Lean; Roy Taylor Journal: Cell Metab Date: 2019-12-19 Impact factor: 27.287
Authors: Ivana Sarac; Katharine Backhouse; Fariba Shojaee-Moradie; Michael Stolinski; M Denise Robertson; Jimmy D Bell; E Louise Thomas; Roman Hovorka; John Wright; A Margot Umpleby Journal: J Clin Endocrinol Metab Date: 2012-04-16 Impact factor: 5.958
Authors: Alison K Wright; Paul Welsh; Jason M R Gill; Evangelos Kontopantelis; Richard Emsley; Iain Buchan; Darren M Ashcroft; Martin K Rutter; Naveed Sattar Journal: Diabetologia Date: 2020-05-21 Impact factor: 10.122
Authors: Mara Suleiman; Lorella Marselli; Miriam Cnop; Decio L Eizirik; Carmela De Luca; Francesca R Femia; Marta Tesi; Silvia Del Guerra; Piero Marchetti Journal: Int J Mol Sci Date: 2022-07-04 Impact factor: 6.208
Authors: Ruixin Zhu; Ionut Craciun; Jan Bernhards-Werge; Elli Jalo; Sally D Poppitt; Marta P Silvestre; Maija Huttunen-Lenz; Melitta A McNarry; Gareth Stratton; Svetoslav Handjiev; Teodora Handjieva-Darlenska; Santiago Navas-Carretero; Jouko Sundvall; Tanja C Adam; Mathijs Drummen; Elizabeth J Simpson; Ian A Macdonald; Jennie Brand-Miller; Roslyn Muirhead; Tony Lam; Pia S Vestentoft; Kristine Færch; J Alfredo Martinez; Mikael Fogelholm; Anne Raben Journal: Diabetologia Date: 2022-05-25 Impact factor: 10.460