Professor Rory McCrimmon

Professor of Experimental Diabetes and Metabolism, Associate Dean of Research (School of Medicine), Deputy Head of Molecular & Clinical Medicine Division

Central regulation of glucose and energy metabolism

Professor Rory McCrimmon

Address:

Division of Molecular & Clinical Medicine
School of Medicine, University of Dundee
Clinical Research Centre
Ninewells Hospital and Medical School
Dundee
DD1 9SY

Phone Number:

+(44) 01382 383444

Email Address:

r.mccrimmon@dundee.ac.uk

Biography

Rory McCrimmon trained at the University of Edinburgh and completed his clinical and speciality training in the South-East of Scotland before becoming an NHS Consultant Physician in Diabetes and Endocrinology at University Hospital Aintree, Liverpool, in 2000. In 2002, he joined the faculty at Yale University, Connecticut, to investigate why people with type 1 and 2 diabetes are very prone to developing low glucose (Hypoglycaemia). He returned to Scotland in 2009 to establish his laboratory at the University of Dundee, where he is currently Associate Dean (Research), Professor of Experimental Diabetes and Metabolism and Honorary Consultant. His major research and clinical interests are in Impaired Awareness of Hypoglycaemia and Exercise in Type 1 diabetes. He was awarded the 2015 RD Lawrence Lecture by Diabetes UK for his research in Hypoglycaemia.

Prof McCrimmon is currently also Lead Clinician for the Scottish Diabetes Research Network (SDRN), which provides the necessary infrastructure to co-ordinate and enable academic and commercial research throughout Scotland. The SDRN hosts a National Research Register of over 11,000 subjects with diabetes pre-consented to be contacted about clinical trials. The register is directly linked to SCI-diabetes, which contains secure clinical and biochemical data on over 350,000 people with diabetes in Scotland.

Prof McCrimmon Serves on Editorial Boards of Diabetologia and Diabetes. He is a panel member for:

 

MRC Populations and Systems Medicine Board

Co-Chair MRC UK – Philippines: Joint Health Research Initiative Call

Diabetes UK, Clinical Studies Group Management Committee

Diabetes UK, Intermediate Clinical Fellowships Panel

Juvenile Diabetes Research Foundation PEAK Programme

International Hypoglycaemia Study Group

 

Research

The primary research of our laboratory in the School of Medicine is in the area of diabetes and metabolic disorders. Within this general field a major focus of the laboratory is in the CNS (brain) mechanisms that underlie glucose-sensing. The three main mechanistic question being addressed by our group are:

“How does the brain sense glucose, especially when levels are low (hypoglycaemia)?”

 “Why do people with type 1 or longer-duration type 2 diabetes lose their ability to recognise hypoglycaemia over time?” A clinical phenomenon referred to as impaired awareness of hypoglycaemia that affects 25% of all people with type 1 diabetes.

 “What are the long-term consequences of repeated exposure to hypoglycaemia in diabetes?”

The laboratories work encompasses basic research in cell culture models as well as translational research in human studies.

Through the Scottish Diabetes Research Network and the Scottish Diabetes Group, our group are also interested in understanding the epidemiology of diabetes in Scotland and in studying pathways of care in diabetes management.

Publications

Last 5 years

  • McCrimmon RJ, Henry RR. SGLT therapy in Type 1 Diabetes. Diabetologia (2018) in press
  • Blonde L, Meneghini L, Peng, XP, Boss A, Rhee K, Shaunik A, Kumar S, Balodi S, Brulle-Wohlhueter C, McCrimmon RJ. Probability of Achieving Glycemic Control with Basal Insulin in Patients with Type 2 Diabetes in Real-World Practice in the USA. Diabetes Therapy (2018) in press.
  • Meakin, P. J., Jalicy, S. M., Montagut , G., Allsop, D., Cavellini, D., Irvine, S. W., McGinley, C., Liddell, M., McNeilly, A., Parmionova, K., Liu, Y-R., Bailey, C. S. L., Dale, J., Heisler, L. K., McCrimmon, R. & Ashford, M. Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice. Scientific Reports (2018) Jan 8;8(1):55. doi: 10.1038/s41598-017-18388-6.
  • McNeilly AD, McCrimmon RJ. Impaired Hypoglycaemia Awareness in Type 1 Diabetes: Lessons from the lab. Diabetologia (2018) Feb 7. doi: 10.1007/s00125-018-4548-8. [Epub ahead of print].
  • Walker J, Colhoun H, Livingstone S, McCrimmon RJ, Petrie J, Sattar S, Wild S. Type 2 diabetes, socio-economic status and life expectancy in Scotland (2012-2014): population-based observational study. Diabetologia (2018) Jan;61(1):108-116. doi: 10.1007/s00125-017-4478-x. Epub 2017 Oct 26.
  • Read, SH, McAllister, DA, Colhoun, HM, Farran, B, Fischbacher, C, Kerssens, JJ, Leese, GP, Lindsay, RS McCrimmon, RJ, McGurnaghan, S, Philip, S, Sattar, S,  Sarah SH. Ischaemic stroke and type 2 diabetes: trends in incidence and case-fatality in Scotland 2004-2013. Diabetic Medicine (2018) Jan;35(1):99-106. doi: 10.1111/dme.13528. Epub 2017 Nov 6.
  • Sharma RS, Harrison DJ, Kisielewski D, Cassidy DM, McNeilly AD, Gallagher JR, Walsh SV, Honda T, McCrimmon RJ, Dinkova-Kostova A, Ashford MLJ, Dillon JD and Hayes JD. Experiment non-alcoholic steatohepatitis and liver fibrosis are ameliorated by pharmacologic activation of Nrf2 (NF-E2-related factor 2). Cellular and Molecular Gastroenterology and Hepatology (2017 - in press).
  • Wild S, Walker JJ, Morling JR, McAllister DA, Colhoun C, Farran B, McGurnaghan S, McCrimmon RJ, Read PhD SR, Sattar S, Byrne CD. Cardiovascular disease, cancer and mortality among people with type 2 diabetes and alcoholic or non-alcoholic fatty liver disease hospital admission. Diabetes Care (2018) Feb;41(2):341-347. doi: 10.2337/dc17-1590. Epub 2017 Nov 22.
  • Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SG, T Diethelm, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. 2017 Lancet Diabetes & Endocrinology (2017) Nov;5(11):864-876. doi: 10.1016/S2213-8587(17)30308-X. Epub 2017 Sep 14.
  • Brown AJM, McCrimmon R, Struthers A. Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study. BMC cardiovascular disorders (2017) Aug 23;17(1):229. doi: 10.1186/s12872-017-0663-6.
  • Mordi NA, Mordi IR, Singh JS, Baig F, Choy AM, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial. BMJ Open (2017) Oct 16;7(10):e018097. doi: 10.1136/bmjopen-2017-018097.
  • Bell, S, Farran, B, McGurnaghan, S, McCrimmon, R, Leese, G, Petrie, JR, McKeigue, PM, Sattar, N, Wild, SH, Lindsay, RS, McKnight, JA, Colhoun, H & Looker, H 2017, Risk of Acute Kidney Injury and Survival in patients treated with Metformin: an observational cohort study BMC Nephrology. (2017) May 19;18(1):163. doi: 10.1186/s12882-017-0579-5. PMID: 28526011
  • Alison D.  McNeilly, Jennifer R. Gallagher, Jeffrey T.-J. Huang, Michael L.J. Ashford, Rory J. McCrimmon. High intensity exercise as a dishabituating stimulus restores counterregulatory responses in recurrently hypoglycemic rodents. Diabetes (2017) Jun;66(6):1696-1702. doi: 10.2337/db16-1533. Epub 2017 Mar 7. PMID: 28270522
  • Julia M. Vlachaki Walker, Josephine L. Robb, Amrinder Malhi, Ana M. Cruz, Paul G. Weightman Potter, Michael L.J. Ashford, Rory J. McCrimmon, Kate L.J. Ellacott, Craig Beall. AMP-activated protein kinase activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner. Diabetes Obes Metab. (2017) Jul;19(7):997-1005. doi: 10.1111/dom.12912. Epub 2017 Apr 21. PMID: 28211632
  • Dadak, S., Beall, C., Vlachaki Walker, J. M., Soutar, M., McCrimmon, R.J & Ashford, M.Oleate induces KATP channel-dependent hyperpolarisation in mouse hypothalamic glucose-excited neurones without altering cellular energy charge. Neuroscience. (2017) Mar 27;346:29-42. doi: 10.1016/j.neuroscience.2016.12.053. PMID: 28087336
  • International Hypoglycaemia Study Group (Stephanie A. Amiel, Pablo Aschner, Belinda Childs, Philip Cryer, Bastiaan de Galan, Simon A. Heller, Brian M. Frier, L Gonder-Frederick, Tomothy Jones, Kamlesh Khunti, Lawrence Leiter, Rory J. McCrimmon, Yingying Luo, Elizabreth Seaquist, Sophia Vigersky, Robert: Zoungas). Glucose concentrations of less than 3.0 mmol/l (54 mg/dl) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the Europian Association for the Study of Diabetes. Diabetologia (2017) 60:3-6.
  • Riddell MC, Gallen IW, Smart CE, Taplin CE, Adolfsson P, Lumb AN, Kowalski A, Rabasa-Lhoret R, McCrimmon RJ, Hume1 C, Annan F, Fournier P, Graham C, Bode B, Galassetti P, Jones TW, San Millan I, Heise T, Peters A, Petz A, and Laffel LM. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol. (2017) May;5(5):377-390. doi: 10.1016/S2213-8587(17)30014-1. PMID: 28126459
  • McCrimmon RJ. Old habits are hard to break: Lessons from the study of hypoglycaemia. Diabetic Medicine (2017) 34 (2):148–15
  • Haythorne, E., Hamilton, D. L., Findlay, J. A., Beall, C., McCrimmon, RJ & Ashford, M. Chronic exposure to KATP channel openers results in attenuated glucose sensing in hypothalamic GT1-7 neurons. Neuropharmacology. (2016) 111:212-222.
  • George, PS, McCrimmon RJ. Saxagliptin co‐therapy in C‐peptide negative Type 1 diabetes does not improve counter‐regulatory responses to hypoglycaemia. Diabetic Medicine (2016). Vol. 33, No. 9, 28.12.2015, p. 1283-1290.
  • Read SH, Kerssens JJ, McAllister DA, Colhoun HM, Fischbacher CM, Lindsay RS, McCrimmon RJ, McKnight JA, Petrie JR, Sattar N, Wild SH; Scottish Diabetes Research Network Epidemiology Group. Trends in type 2 diabetes incidence and mortality in Scotland between 2004 and 2013. Diabetolgia (2016) Oct;59(10):2106-13.
  • McNeilly AD, Gallagher JR, Dinkova-Kostova AT, Hayes JD, Sharkey J, Ashford MLJ, McCrimmon RJ. Nrf2-mediated neuroprotection against recurrent hypoglycemia is insufficient to prevent cognitive impairment in a rodent model of type 1 diabetes. Diabetes (2016) Oct;65(10):3151-60
  • Aucott LS, Philip S, Avenell A, Afolabi E, Sattar N, Wild S, Emslie Smith Fischbacher C, Cunningham S, Looker H, Colhoun H, Petrie J, McKnight J, Lindsay R, McCrimmon RJ, Leese G, Scottish Diabetes Research Network Epidemiology Group. Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes; a retrospective cohort study. BMJ Open (2016) e010836.
  • Yavari, A., C. J. Stocker, S. Ghaffari, E. T. Wargent, V. Steeples, G. Czibik, K. Pinter, M. Bellahcene, A. Woods, P. B. Martinez de Morentin, C. Cansell, B. Y. Lam, A. Chuster, K. Petkevicius, M. S. Nguyen-Tu, A. Martinez-Sanchez, T. J. Pullen, P. L. Oliver, A. Stockenhuber, C. Nguyen, M. Lazdam, J. F. O'Dowd, P. Harikumar, M. Toth, C. Beall, T. Kyriakou, J. Parnis, D. Sarma, G. Katritsis, D. D. Wortmann, A. R. Harper, L. A. Brown, R. Willows, S. Gandra, V. Poncio, M. J. de Oliveira Figueiredo, N. R. Qi, S. N. Peirson, R. J. McCrimmon, B. Gereben, L. Tretter, C. Fekete, C. Redwood, G. S. Yeo, L. K. Heisler, G. A. Rutter, M. A. Smith, D. J. Withers, D. Carling, E. B. Sternick, J. R. Arch, M. A. Cawthorne, H. Watkins and H. Ashrafian Chronic Activation of gamma2 AMPK Induces Obesity and Reduces beta Cell Function. Cell Metab (2016) 23(5): 821-836.
  • Wilkin T, Greene S, McCrimmon R. Testing the accelerator hypothesis: a new approach to type 1 diabetes prevention (adAPT 1). Diabetes Obes Metab. (2016) Jan;18(1):3-5. PubMed PMID: 26511442.
  • McNeilly AD, McCrimmon RJ. The Scylla and Charybdis of glucose control in childhood type 1 diabetes? Pediatr Diabetes. (2015) Jun;16(4):235-41. PubMed PMID: 25727089.
  • Malik MO, Govan L, Petrie JR, Ghouri N, Leese G, Fischbacher C, et al. Ethnicity and risk of cardiovascular disease (CVD): 4.8 year follow-up of patients with type 2 diabetes living in Scotland. Diabetologia. (2015) Apr;58(4):716-25. PubMed PMID: 25669630.
  • Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. (2015) Jan 6;313(1):37-44. PubMed PMID: 25562264. Pubmed Central PMCID: 4426486.
  • George PS, Tavendale R, Palmer CN, McCrimmon RJ. Diazoxide improves hormonal counterregulatory responses to acute hypoglycemia in long-standing type 1 diabetes. Diabetes. (2015) Jun;64(6):2234-41. PubMed PMID: 25591873.
  • Meakin PJ, Chowdhry S, Sharma RS, Ashford FB, Walsh SV, McCrimmon RJ, et al. Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance. Mol Cell Biol. (2014) Sep;34(17):3305-20. PubMed PMID: 24958099. Pubmed Central PMCID: 4135558.
  • McCrimmon RJ. The challenges of hypoglycemia in the community. Diabetic Hypoglycemia. (2014) 1;6(3):1.
  • McCrimmon RJ. Challenges associated with exercise in type 1 diabetes. Diabetic Hypoglycemia. (2014) 6;7(1):1-2.
  • McNay EC, Teske JA, Kotz CM, Dunn-Meynell A, Levin BE, McCrimmon RJ, et al. Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance. a model for weight gain with intensive insulin therapy. Am J Physiol Endocrinol Metab (2013) 1/15;304(2):E131-E8.
  • George P, McCrimmon RJ. Potential role of non-insulin adjunct therapy in Type 1 diabetes. Diabetic Medicine. (2013) 2/1;30(2):179-88.
  • George P, McCrimmon RJ. Avoiding hypoglycemia during protracted physical exercise by utilizing modern technology. Diabetic Hypoglycemia. (2013) 2/28;5(3):12-4.
  • Gardiner A, George PS, Pearson E, McCrimmon RJ. An interesting case of new-onset ketosis-prone diabetes in a Scottish teaching hospital. British Journal of Diabetes and Vascular Disease. (2013) 10/1;13(5-6):265-8.
  • Beall C, Watterson KR, McCrimmon RJ, Ashford MLJ. AMPK modulates glucose-sensing in insulin-secreting cells by altered phosphotransfer to KATP channels. Journal of Bioenergetics and Biomembranes. (2013) 6;45(3):229-41.
  • Beall C, Haythorne E, Fan X, Du Q, Jovanovic S, Sherwin R, et al. Continuous hypothalamic KATP channel activation blunts glucose counter-regulation in vivo in rats and suppresses KATP conductance in vitro. Diabetologia. (2013) 9;56(9):2088-92.
  • Yang L, Isoda F, Yen K, Kleopoulos SP, Janssen W, Fan X, et al. Hypothalamic Fkbp51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes. American Journal of Physiology, Endocrinology and Metabolism. (2012);302(8):E987-E91.
  • McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet. (2012) 6/16;379(9833):2291-9.
  • McCrimmon RJ, Oz G. Cerebral adaption to recurrent hypoglycemia. Translational Endocrinology and Metabolism. Chevy Chase, MD: Endocrine Society; (2012). p. 89-114.
  • George P, McCrimmon RJ. Diazoxide. Practical Diabetes International. (2012) 1/1;29(1):36-7.
  • McCrimmon RJ. Update in the CNS response to hypoglycemia. Journal of Clinical Endocrinology & Metabolism. (2012) 1/1;97(1):1-8.
  • George PS, McCrimmon RJ. Therapeutic strategies to prevent hypoglycemia using pharmacologic interventions. Diabetic Hypoglycemia. (2012) 10;5(2):13-6.
  • Beall C, Hamilton DL, Gallagher J, Logie L, Wright K, Soutar MP, et al. Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour. Diabetologia. (2012) 9;55(9):2432-44.
  • Beall C, Ashford ML, McCrimmon RJ. The physiology and pathophysiology of the neural control of the counterregulatory response. American Journal of Physiology: Regulatory Integrative and Comparative Physiology. (2012) 1;302(2):R215-R23.
  • Ashford M, Beall C, McCrimmon RJ. Hypoglycaemia: exercise for the brain? Journal of Neuroendocrinology (2012) 10;24(10):1365-6.

 

Teaching

Primary teaching role is in academic mentoring and supervision of clinicians and undergraduates, as well as delivery of lectures as part of the undergraduate and post-graduate training in Diabetes and Endocrinology.

PhD Supervision

Current:

Dr Catriona Farrell

Charvi Nangia

Completed:

Elizabeth Hawthorne (2010-2014)

Dr Priya George (2011-2015)

Geoffrey Denwood (2011-2015)

Adonis Yiannakas (2012-2015)

Harriet Johnston (2010-2012)

 

Conferences

Last 5 years (International)

05/18                     Hypoglycaemia: Forget about it! University of Copenhagen, Denmark.

12/17                     What do clinicians need to know about hypoglycaemia. Meet the expert. IDF, Abu Dhabi, UAE

09/17                     Impaired awareness of hypoglycaemia: New discoveries and treatments, EASD, Lisbon, Portugal.

09/16                     Clinical Inertia: Lessons from Scotland, EASD, Munich, Germany.

09/16                     Exercise in Type 1 Diabetes: JDRF PEAK Program Overview, Munich, Germany.

04/16                     Physiology of Exercise in Type 1 Diabetes; JDRF PEAK, Boston, US.

02/16                     Impaired hypoglycaemia awareness: The habit of a lifetime. Steno Diabetes Centre, Denmark.

10/15                     Impaired hypoglycaemia awareness: The habit of a lifetime. International Society of Paediatric and Adolescent Diabetes, Brisbane, Australia.

03/15                     Cerebral adaption to recurrent hypoglycaemia. Levine Symposium, San Diego, USA.

08/14                     The Scylla and Charybdis of glucose control in Type 1 Diabetes. Norwegian Diabetes Meeting, Oslo.

01/14                     Hypoglycaemia: The study of stress, starvation and tolerance. 3U Meeting, Dublin.

12/13                     Diabetes and Dementia, IDF, Melbourne, Australia, Keynote lecture.

10/13                     The highs and lows of metabolic stress in type 1 diabetes. International Society of Paediatric and Adolescent Diabetes Gothenberg, Sweden.

10/12                     Another piece of the jigsaw: How the brain regulates pancreatic endocrine function. International Society of Paediatric and Adolescent Diabetes conference, Istanbul, Turkey.

09/12                     Hypoglycaemia Tolerance: An adaptive response to repeated hypoglycaemia, National Diabetes Symposium, Helsinki, Finland.

03/12                     Hypoglycaemia and the brain: does age play and important role. Lilly peaks and Valleys meeting, Kuala Lumpur, Malaysia.

04/12                     Hypoglycaemia and the brain: does age play and important role. Lilly peaks and Valleys meeting, Amsterdam, Holland.

08/12                     Hypoglycaemia and the brain: does age play and important role. Lilly peaks and Valleys meeting, Santiago, Chile.

Group Alumni

Dr Ligang Zhou – Professor and Director of Department of Endocrinology, Shuguang hospital, Shanghai, China.

Dr Haiying Cheng - Assistant Professor, Dept of Oncology, Albert Einstein College of Medicine

Dr Craig Beall -  Diabetes UK RD Lawrence Fellow