The Diabetes Research Group in Newcastle has applied magnetic resonance spectroscopy and imaging to explain the abnormal storage of fat and glycogen in pancreas, liver and muscle in Type 2 diabetes.
Type 2 diabetes is escalating as a national public health problem, and the rapidly rising incidence in younger people will certainly be followed by premature coronary and stroke disease.
Our work has shown that Type 2 diabetes is caused by abnormal fat storage accumulation in the pancreas. Research on how Type 2 may be reversed is available. Application of a newly developed magnetic resonance method has allowed the importance of the pancreas fat content to be evaluated.
Other current studies have allowed identification of the failure of muscle glycogen storage and abnormal storage of fat in muscle after eating in Type 2 diabetes. This work is revolutionising concepts of intra-organ energy storage after eating both in normal health and in diabetes. Additionally it has been demonstrated that DPP-4 inhibitors (specifically Vildagliptin) decrease liver fat stores.
We have shown that there is no intrinsic abnormality in mitochondrial ATP production in muscle of people with Type 2 diabetes.
We have developed methods to evaluate kidney disease in diabetes.
View Prof Roy Taylor's staff profile.
Current and planned work
The DiRECT study will find out how well reversal of Type 2 diabetes works when done by Practice Nurses in General Practice. It is a cluster randomised controlled trial which will also define how durable is the return to normal glucose control, how people cope with the programme and what underlying changes in liver and pancreas determine outcome. Visit the DiRECT website.
Studies of the effect of exercise training on the previously defined abnormal muscle metabolism in Type 2 diabetes.
These studies have been supported by:
- Diabetes UK
- the Diabetes Research and Wellness Foundation
- the Wellcome Trust
- Novartis Pharma AG
- the European Foundation for the Study of Diabetes
Remission of type 2 diabetes with Total Diet Replacement and long-term maintenance, within routine NHS care (DiRECT – Diabetes REmission Clinical Trial).
Project Leader(s): Professor Roy Taylor
Project Dates: From April 2014
- Taylor R, Barnes A. Translating aetiological insight into sustainable management of type 2 diabetes? Diabetologia 2017 In press.
- Al-Mrabeh A, Hollingsworth KG, Steven S, Tiniakos D and Taylor R. Quantification of intrapancreatic fat in type 2 diabetes by MRI. PLOS One. April 3, 2017https://doi.org/10.1371/journal.pone.0174660.
- Hodson K, Dalla Man C, Smith FE, Barnes A, McParlin C, Cobelli C, Robson SC, Araujo-Soares V, Taylor R. Liver triacylglycerol content and gestational diabetes: Effects of moderate calorie restriction. Diabetologia. 2017 Feb;60(2):306-313. doi: 10.1007/s00125-016-4143-9. PMID: 27817155.
- Leslie WS, Taylor R, Harris L, Lean M. Weight losses with low energy formula diets in obese patients with and without type 2 diabetes: Systematic review and meta-analysis. Int J Obes (Lond). 2017; 41:96-101. doi: 10.1038/ijo.2016.175.
- White MG, Shaw JAM, Taylor R. Type 2 diabetes: The pathologic basis of reversible beta-cell dysfunction. Diabetes Care 2016; 39:2080-88. doi 10.2337/dc16-0619.
- Steven S, Hollingsworth KG, Small PK, Woodcock SA, Pucci A, Aribisala B, Al-Mrabeh A, Batterham RL, Taylor R. Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes. Diabet Med. 2016 Dec;33(12):1723-1731. doi: 10.1111/dme.13257. Epub 2016 Oct 8.
- Al-Mrabeh A, Hollingsworth KG, Steven S, Taylor R. Morphology of the pancreas in type 2 diabetes: effect of weight loss with or without normalisation of insulin secretory capacity. Diabetologia. 2016 Aug;59(8):1753-9. doi: 10.1007/s00125-016-3984-6. [Epub 2016 May 14].
- Avery L, Charman S, Taylor L, Flynn D, Mosely K, Speight J, Lievesley M, Taylor R, Sniehotta F, Trenell M. Systematic development of a theory-informed multifaceted behavioural intervention to increase physical activity of adults with type 2 diabetes in routine primary care: Movement as Medicine for Type 2 Diabetes. Implementation Science. 2016 Jul 19;11:99. doi: 10.1186/s13012-016-0459-6.
- Steven S, Hollingsworth KG, Al-Mrabeh A, Avery L, Aribisal B, Caslake M and Taylor R. Very-Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiologic Changes in Responders and Nonresponders. Diabetes Care. 2016 May;39(5):808-15. doi: 10.2337/dc15-1942. Epub 2016 Mar 21. PMID: 27002059.
- Steven S, Hollingsworth KG, Small PK, Woodcock SA, Pucci A, Aribisala B, Al-Mrabeh A, Daly AK, Batterham RL, Taylor R. Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type 2 Diabetes. Diabetes Care. 2016 Jan;39(1):158-65. doi: 10.2337/dc15-0750. Epub 2015 Dec 1. PMID: 26628414.
- Steven S, Hollingsworth KG, Small PK, Woodcock SA, Pucci A, Aribasala A, Al-Mrabeh A, Batterham RL and Taylor R. Increased GLP-1 at 7 days following RYGB does not translate into improved insulin secretion rates or glucose control compared to 7 days of VLCD.
- Wilma Leslie; Ian Ford; Naveed Sattar; Kieren Hollingsworth; Ashley Adamson; Falko Sniehotta; Louise McCombie; Naomi Brosnahan; Hazel Ross; John Mathers; Carl Peters; George Thom; Alison Barnes; Sharon Kean; Yvonne McIlvenna; Angela Rodrigues; Lucia Rehackova; Sviatlana Zhyzhneuskaya; Roy Taylor; Mike Lean. The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial. BMC Family Practice. 2016 Feb 16;17:20. doi:10.1186/s12875-016-0406-2. PMID: 26879684.
- Cassidy S, Thoma C, Hallsworth K, Parikh J, Hollingsworth KG, Taylor R, Jakovljevic DG, Trenell MI. High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2016 Jan;59(1):56-66. doi: 10.1007/s00125-015-3741-2. Epub 2015 Sep 9.
- Steven S, Taylor R. Restoring normoglycaemia by use of a very low calorie diet in long- and short-duration Type 2 diabetes. Diabet Med. 2015 Feb 12. doi: 10.1111/dme.12722. [Epub ahead of print]. PMID: 25683066.
- Macauley M, Hollingsworth KG, Smith FE, Thelwall PE, Al-Mrabeh A, Schweizer A, Foley JE, Taylor R. Effect of Vildagliptin on Hepatic Steatosis. J Clin Endocrinol Metab. 2015 Feb 12. doi: 10.1111/dme.12722. PMID: 25683066.
- Macauley M, Percival K, Thelwall PE, Hollingsworth KG, Taylor R. Altered volume, morphology and composition of the pancreas in type 2 diabetes. PLOS ONE. 2015. In Press.
- Steven S, Carey PE, Small PK, Taylor R. Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short- and long-duration diabetes. Diabetic Medicine. 2015 Jan; 32(1):47-53. doi: 10.1111/dme.12567. Epub 2014 Sep 12. PMID: 25132043.
- Macauley M, Smith FE, Thelwall P, Taylor R. Diurnal variation in skeletal muscle and liver glycogen in humans with normal health and type 2 diabetes. Clinical Science. 2015 Jan 13. PMID: 25583442. In Press.
- Talks J, Manjunath V, Steel DHW, Peto T, Taylor R. New vessels detected on wide field imaging compared to 2-field and 7-field imaging: implications for diabetic retinopathy screening image analysis. Br J Ophthalmol 2015 doi:10.1136/bjophthalmol-2015-306719.
- Cassidy S, Hallsworth K, Thoma C, MacGowan GA, Hollingsworth KG, Day CP, Taylor R, Jakovljevic DG, Trenell MI. Cardiac structure and function are altered in Type 2 diabetes and Non-alcoholic fatty liver disease and associate with glycemic control. Cardiovasc Diabetol. 2015 Feb 13;14:23. doi: 10.1186/s12933-015-0187-2.
- Hodson K, DellaMan C, Smith FE, Thelwall PE, Cobelli C, Robson SC, Taylor R. Mechanism of insulin resistance in normal pregnancy. Horm Metab Res. 2013 Aug;45(8):567-71. doi: 10.1055/s-0033-1337988. Epub 2013 Apr 2. PMID: 23549674.
- Avery L, Sniehotta FF, Denton SJ, Steen N, McColl E, Taylor R, Trenell MI. Movement as Medicine for Type 2 Diabetes: protocol for an open pilot study and external pilot clustered randomised controlled trial to assess acceptability, feasibility and fidelity of a multifaceted behavioural intervention targeting physical activity in primary care. Trials 2014 Feb 3; 15:46. doi: 10.1186/1745-6215-15-46. PubMed PMID: 24491134.
- Taylor R. Type 2 Diabetes: Etiology and Reversibility. Diabetes Care. 2013 Apr;36(4):1047-55. doi: 10.2337/dc12-1805. PubMed PMID: 23520370.
- Taylor R. Reversing the Twin Cycles of Type 2 Diabetes: The Banting Lecture 2012. Diabet Med. 2013 Mar;30(3):267-75. doi: 10.1111/dme.12039. PubMed PMID: 23075228.
- Steven S, Lim EL, Taylor R. Population response to information on reversibility of Type 2 diabetes. Diabet Med. 2013 Jan 15. doi: 10.1111/dme.12116. [Epub ahead of print].
- Knop F, Taylor R. Mechanism of metabolic advantage after bariatric surgery - it’s all gastrointestinal factors vs. it’s all food restriction. Diabetes Care. 2013 Aug;36 Suppl 2:S287-91. doi: 10.2337/dcS13-2032. PubMed PMID: 23882061.
- Taylor R. Insulin resistance and type 2 diabetes. Diabetes. 2012 Apr;61(4):778-9. doi: 10.2337/db12-0073. PubMed PMID: 22442298.
- Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011 Jun 9.
- Lim EL, Hollingsworth KG, Smith F, Thelwall PE, Taylor R. Inhibition of lipolysis in type 2 diabetes normalizes glucose disposal without change in muscle glycogen synthesis rates. Clin. Sci. 2011; 121: 169-177.
- Lim EL, Hollingsworth KG, Smith F, Thelwall PE, Taylor R. Effects of raising muscle glycogen synthesis on skeletal muscle ATP turnover rate in type 2 diabetes. American J Physiology 2011 PMID 21917633.
- Thelwall PE, Taylor R, Marshall SM. Non-invasive investigation of kidney disease in Type 1 diabetes by magnetic resonance imaging. Diabetologia 2011; 54(9):2421-9.
- Taylor R. Reversing Type 2 diabetes. Practical Diabetes 2011; 28: 377-378.
- Lim EL, Hollingsworth KG, Thelwall P, Taylor R. Measuring the acute effect of insulin infusion on ATP turnover rate in human skeletal muscle using phosphorus-31 magnetic resonance saturation transfer spectroscopy. NMR in Biomedicine 2010; 23:952-7.
- Chen MJ, Jovanovic A, Taylor R. Utilizing the Second-Meal Effect in Type 2 Diabetes: Practical Use of a Soya-Yogurt Snack. Diabetes Care 2010; 2552-54.
- Steven S, Lim EL, Taylor R. Reversal of type 2 diabetes. Diabetic Medicine 2010; 27: 724-725.
- Balasubramanian R, Gerrard J, Dalla Man C, Firbank MJ, Lane A, English PT, Cobelli C, Taylor R. Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content. Diabetic Medicine 2010; 27:150-156.
- Hayes L, Pearce MS, Firbank MJ, Walker M, Taylor R, Unwin N. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study. BMC Public Health. 2010; 10:723.
- Jovanovic A, Leverton E, Solanky B, Snaar JEM, Morris PEG, Taylor, R. The second meal phenomenon is associated with enhanced muscle glycogen storage. Clin. Sci. 2009 Jul 2;117(3):119-27.
- Jovanovic A, Gerrard, J., Taylor, R. The second meal phenomenon in type 2 diabetes. Diabetes Care 2009 Jul;32(7):1199-201.
- Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia. 2008;51(10):1781-9.
- Trenell MI, Hollingsworth KG, Lim EL, Taylor R. Increased daily walking improves lipid oxidation without changes in mitochondrial function in type 2 diabetes. Diabetes Care. 2008 Aug;31(8):1644-9.
- Sorensen L, Siddall PJ, Trenell MI, Yue DK. Differences in Metabolites in Pain-Processing Brain Regions in Patients With Diabetes and Painful Neuropathy. Diabetes Care. 2008 May 1, 2008;31(5):980-1.
- Lim, E; Trenell, MI; Hollingsworth, KG; Smith, FE; Thelwell, PE; Taylor, R. Is the sub-normal insulin stimulation of muscle ATP synthesis in type 2 diabetes always a consequence of low rates of muscle glycogen synthesis? Diabetologia 51: 766 (2008).
- Trenell, MI; Thelwall, P; Thomas, K; Stevenson, E. Effect of high and low glycaemic index diets on skeletal muscle and liver substrate storage and utilisation during exercise. Diabetologia 51: 248 (2008).
- Ravikumar B, Gerrard J, Man CD, Firbank MJ, Lane A, English PT, et al. Poglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content. Diabetes 2008; 57(9):2288-95.
- Ravikumar B, Gerrard J, English PT, Firbank MJ, Taylor R. Combination therapy with PPARgamma and PPARalpha agonists in Type 2 diabetes improves glucose and lipid metabolism independent of changes in tissue triglyceride content. Diabetic Medicine. 2007;24:43-.
- Jovanovic A, Gerrard J, Taylor R. Therapeutic application of the second meal effect in Type 2 diabetes. Diabetic Medicine. 2007;24:21-.