DIABETES and ENDOCRINOLOGY
Name and Title of Academic Director
Professor Solomon Tesfaye
Overview of Experimental Medicine Research in Theme

Main themes
Diabetes
a)
b)
c)
d)
Hypoglycaemia
Studies in Type 1 diabetes
CNS imaging and diabetes
Biomarkers of diabetic autonomic neuropathy
Endocrinology
e) Endocrine hormone replacement.
f) Treatment of hormone excess.
Overview
In hypoglycaemia we are planning to develop our work undertaking mechanistic studies
which might explain mortality in both types of diabetes. We have entered into a collaborative
research agreement with Eli Lilly, Indianapolis to develop this work in joint studies and are
contributing to work with them and the FDA in clarifying the relevance of abnormal cardiac
repolarisation in diabetes when developing new medications. We are planning collaborative
studies exploring mechanisms of hypoglycaemia unawareness and closed loop treatment in
Type 1 diabetes.
In diabetic neuropathy we will be initiating novel studies that will identify objective, perfusion
and fMRI correlates of pain in diabetes to develop of new and more effective analgesic
compounds in painful diabetic neuropathy. In autonomic neuropathy we will explore the
potential of heart rate variability as a predictor of autonomic neuropathy in prospective work
and determine whether intensive intervention including new medication can prevent
established neuropathy.
In endocrinology our main goal is to translate new endocrine therapies into commercial
products by 2017 including, Chronocort treatment of congenital adrenal hyperplasia and
adrenal insufficiency, Infacort for the treatment of neonatal and infant congenital adrenal
hyperplasia and adrenal insufficiency, High dose vitamin D for the replacement of vitamin D
deficiency, glucocorticoid antagonists for the treatment of sub clinical Cushing’s disease and
siRNA as therapy for Cushing’s disease.
Achievements
Hypoglycaemia and studies in Type 1 diabetes - We have published data from the
ADVANCE database in a paper in the NEJM demonstrating an association between severe
hypoglycaemia and subsequent mortality, which together with data from the ACCORD and
VADT trials underpins our EM work exploring potential mechanisms in mortality. On the
strength of this work and pilot data, our academic clinical fellow has been awarded a 3 year
1
PhD fellowship by the NIHR to complete these studies. We have published over 50 peer
review papers over the last 5 years and attracted over £6m in grant funding.
CNS Imaging and Autonomic neuropathy We have demonstrated uniquely, spinal cord
atrophy in the neuropathic process and found that this process is early, found even in those
with sub clinical (early) neuropathy. We have recently reported the involvement of the brain
by demonstrating: a) the presence of thalamic neuronal dysfunction in DPN using MR
Spectroscopy, and b) impaired thalamic blood flow in those with painless DPN and
increased thalamic vascularity in those with painful DPN by using MR perfusion imaging.
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes and carries up to
a five-fold increased risk of mortality. We have developed a simple test 5 min test for
subclinical CAN, based on Spectral Analysis of Heart Rate Variability which may allow the
identification of high risk subjects. This test also was found to differentiate patients with
painful from painless diabetic neuropathy. We have published over 40 peer reviewed papers
in the last 5 years and generated >£1m of grant funding.
Endocrine hormone replacement and treatment of hormone excess. We have
developed new therapies for adrenal insufficiency including congenital adrenal hyperplasia,
developing chronocort a new modified release formulation of hydrocortisone. We have
obtained orphan drug designation for chronocort. We have established University of
Sheffield spin out company Diurnal Ltd to develop chronocort in collaboration with the
University of Sheffield. Obtained 5.6 million euro framework 7 EU grant to develop neonatal
infant preparation of hydrocortisone (infacort) as principle investigator and the University of
Sheffield as co-ordinator of the study. We have recently initiated a study in testosterone
replacement in young male cancer survivors (TRYMS). We have developed a long acting
growth hormone agonist and antagonist, currently in preclinical phase with expectation of
phase 1 clinical studies in 2013 backed by a University spin out company Asterion Ltd that
has over 25 granted patents in this area. We have developed a novel strategy to treat
Cushing’s disease using siRNA for which orphan drug designation has been granted from
EMA. We are developing a translational research partnership (TRP) with nine other major
UK centres. We have published over 40 peer reviewed papers in the last 5 years and
attracted >£5million grant funding.
Infrastructure
We are currently supported by two research nurses and two part time administrators. We
are currently advertising for a Research Coordinator to support writing of research
applications and helping investigators in the Dept to guide projects through the research
process and ensure that studies are undertaken to a high quality.
Experimental Medicine Research Strategy in Theme X 2012-2017
Short, medium and long term plans

Hypoglycaemia and Type 1 diabetes studies (Prof Simon Heller)
1. Pathophysiology of insulin induced hypoglycaemia
a. We have funding in place to study basic potential mechanisms
(electrophysiological, inflammatory, rheological) of mortality in individuals with
Type 2 diabetes using an experimental human model (hyperinsulinaemic
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2.
3.
4.
5.
glucose clamp) and ambulatory studies involving continuous glucose
monitoring and ambulatory ECGs.
b. We are also currently undertaking EM studies exploring the contribution of
autonomic neuropathy to hypoglycaemia unawareness and the responses of
the autonomic nervous system during experimental hypoglycaemia.
We are planning EM studies to supplement an epidemiological survey measuring the
pathophysiological responses of first degree relatives of victims of the dead in bed
syndrome in those with Type 1 diabetes.
We are currently engaged in a Hypo-Compass trial (multicentre, funded by Diabetes
UK) in which patients with hypoglycaemia unawareness are randomised to
continuous glucose monitoring, pump therapy or education. In a sub study funded
within the grant we are exploring the effect of autonomic neuropathy which requires
additional glucose clamping in patients with unawareness, Type 1 diabetic controls
and non-diabetic controls.
We are funded by a Diabetes UK grant in a multicentre study to undertake the first
ambulatory trial of a closed loop device and insulin pump designed to control blood
glucose automatically in adults with Type 1 diabetes (ANGELA 3). This will involve
assessment and monitoring (including overnight stays in the CRF) before a period of
ambulatory evaluation in patients who take the device home.
Studies in newly diagnosed Type 1 diabetes
 We are anticipating being the lead UK site (in collaboration with Dr John
Snowdon the Dept of Haemato-oncology) of myelosupressive therapy and
autologous bone marrow transplantation in an attempt to maintain insulin
secretion and insulin independence in newly diagnosed patients with Type 1
diabetes.
 We are also co-applicants on an application to HTA proposing a trial of a
GLP-1 analogue in newly diagnosed individuals with Type 1 diabetes. This
tests the hypothesis that such agents will maintain both endogenous insulin
and the glucagon response to hypoglycaemia.
1. CNS Imaging and diabetes (Prof Solomon Tesfaye)
In a 5 year program grant we now want to determine: 1) the microvascular perfusion
characteristics of the thalamus and other areas of the pain matrix in type 1 diabetic
subjects with painful diabetic neuropathy, both at the resting state and in response to
acute pain, and 2) the effect of improvement in the intensity of painful symptoms on
microvascular perfusion of the thalamus and other areas of the pain matrix in
subjects with painful diabetic neuropathy and 3)the effect of improvement in the
intensity of painful symptoms on fMRI correlates of painful diabetic neuropathy. The
proposed work will be the first one to initiate entirely novel studies that will identify
objective, perfusion and fMRI correlates of pain in diabetes with great potential for
the development of new and more effective analgesic compounds that specifically
target key pathological correlates of painful diabetic neuropathy. We are taking a lead
in this proposal that will also include investigators from the Mayo Clinic (Prof PJ
Dyck) and University of Oxford FMRIB (Prof I Tracey).
2. Biomarkers of diabetic autonomic neuropathy (Prof Solomon Tesfaye)
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The main aims of our 5-year, multi-centre, prospective study are to: 1) determine the
concurrent validity of SHRV as a sensitive biomarker of early (subclinical) CAN in a
cross-sectional study, 2) determine the predictive validity of SHRV as a biomarker
of the future development of established CAN in a prospective study and 3)
determine if intensive, multi-factorial intervention including the use of a novel statin/
fenofibrate combination prevents the development of established CAN. On the basis
of current CAN Gold standards baroreceptor sensitivity test (BRS) and AFTs, age
and sex matched type 1 patients will be allocated to groups with: 1) no CAN with
normal BRS and AFTs, 2) subclinical CAN with abnormal BRS but normal AFTs and
3) established CAN with abnormal BRS and AFTs. The ability of SHRV to diagnose
subclinical CAN will be tested. A group of matched healthy volunteers will also be
recruited for comparison. These 4 groups will be followed for 3 years. The ability of
SHRV to predict the development of established CAN will be tested in the
prospective study. A subsection of subjects with subclinical CAN will undergo
intensive multi-factorial treatment for a period of 3 years. Thus the proposal will
simultaneously interrogate if a simple test can identify high risk diabetic subjects
for CAN and if such patients can benefit from a novel, intensive multi-factorial
therapy, and may have a major impact for the screening and management of CAN
in diabetic patients.

Endocrinology (Prof Richard Ross, Dr John Newell-Price)
The main goal is to translate new endocrine therapies into commercial products by
2017 these include:
1. Chronocort for the treatment of congenital adrenal hyperplasia and adrenal insufficiency.
2. Infacort for the treatment of neonatal and infant congenital adrenal hyperplasia and
adrenal insufficiency.
3. High dose vitamin D for the replacement of vitamin D deficiency – Innovation opportunity
with D3 Pharma.
4. Glucocorticoid antagonists for the treatment of sub clinical Cushing’s disease and as a
diagnostic test to stratify patients with functioning adrenal incidentalomas.
5. siRNA as therapy for Cushing’s disease
How will the CRF facilitate this strategy
The CRF will be crucial to conducting the detailed physiological studies described in this
document. These include the detailed physiological studies involving glucose clamps
and measurements of autonomic function. The imaging studies are generally conducted
in the academic dept of radiology which is where the MRI facilities are housed.
However, where research nurses are needed to support this work, these can be provided
either from the CRF research nurse complement or those research nurses who although
based in the Diabetes/Endocrine Dept, work under the auspices of the CRF. The CRF
will be crucial to the first in man studies of siRNA therapy. Phase 1, 2 and 3 studies for
chronocort, infacort, vitamin D and glucocorticoid antagonists will also be undertaken in
the CRF.
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Markers of esteem
Simon Heller
Chairman – Clinical Studies Advisory Committee, Diabetes Research Network
Member – Diabetes UK Research Committee
Member of Diabetes UK Scientific and Research Advisory Group
Member of HTA
Member of Juvenile Diabetes Foundation International, UK Advisory Committee
Solomon Tesfaye:
Chairman – Neurodiab (largest global neuropathy study group)
2006- 2009
Chairman - International Expert Group on Diabetic Neuropathy
2009Vice Chairman - Science and Research Committee of Diabetes UK
2010External reviewer of the NICE guidelines for management of diabetic neuropathies (2008)
and committee member for the neuropathic pain panel in 2010
Executive Committee member of the UK Neuropathy Trust
2004Member of Global Quantitative Sensation Testing Society; Sets Global Standards 2005-To
date. www.qst-s.org
Trustee of International Insulin Foundation (IIF) http://www.access2insulin.org/ 2007-To date
Associate Editor of Diabetologia 2001-2003 (Journal of the European Association for the
Study of Diabetes).
Associate Editor of J Experimental Research
2009-To date
Associate Editor of Frontiers in Endocrinology
2011Richard Ross
Chairman of UK Congenital Adrenal Hyperplasia Cohort CaHASE,
Executive Council European Society for Endocrinology
Council Member Growth Hormone Research Society,
Nominations Committee Society for Endocrinology
Faculty Lead for Innovation.
John Newell-Price
Principle Investigator Endocrine Translational Partnership NOCRI
Chair of the Corporate Liaison Board, Society for Endocrinology
Chair Joint Speciality Committee for Endocrinology and Diabetes Royal College of
Physicians
Executive Committee of the UK and Ireland Neuroendocrine Tumour Society
Member NIHR CRN (Yorkshire) Metabolic and Endocrine Specialty Group
Associate Editor ‘Clinical Endocrinology’
Editorial Board Journal of Clinical Endocrinology and Metabolism.
Strategic partnerships – including those with industry
Pfizer
Diurnal Ltd and Asterion Ltd
Endocrine Translational Partnership
HRA Pharma
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Novartis
JDRF
Diabetes UK
NIH
Pfizer
Eli Lilly and company
NovoNordisk
Track record in and plans for patient and public involvement
Simon Heller has set up a patient user group to support an NIHR programme grant.
Late Effects Group Sheffield (LEGS) – appointed first nurse consultant in late effects and
setting national and international standards for late effect.
Trustee of Pituitary Foundation (JNP) (patient support charity) with dissemination of research
at their National meeting (Nov 5th 2012)
Solomon Tesfaye is President of the Sheffield Diabetes UK patients’ group and gives regular
annual lectures (including one on user involvement in research in 2010). He is also Trustee
of the Neuropathy Trust which the largest neuropathy patients association in the UK and
Europe.
Current or recent grant funding
Irish Health Board. April 2006-March 2012. Implementing and evaluating a
structured education programme and a new model of ongoing care for Type 1
diabetes in Ireland. In collaboration with Dr S Dinneen, Dr H Courtney, Dr D O’Shea,
Prof CP Bradley, Dr K Murphy, Prof E O’Shea, Ms D Casey, Dr J Lawton, Ms F
Brown, Dr J Newell
1m euros
STH Special Trustees. April 2006-March 2008. Exploring abnormal cardiac
repolarization during hypoglycaemia in Type 1 diabetes. Principal Investigator in
collaboration with Dr C Newman.
£20,000
Diabetes UK. May 2006-April 2009. Does self monitoring of blood glucose as
opposed to urinalysis provide additional benefit to newly diagnosed individuals with
Type 2 diabetes receiving structured education? Principal Investigator in
collaboration with Dr M Carey, Dr M Davies, Prof M Campbell, Dr S Dixon, Dr C
Skinner, Dr H Dallasso, Dr E Pitchforth
£350,000
Diabetes UK. October 2006-September 2008. Exploring abnormal cardiac
repolarization during hypoglycaemia in Type 1 diabetes. Principal Investigator in
collaboration with Dr C Newman, Prof Ian Macdonald
£124,000
National Institute of Health Research, Programme Grant October 2007-September
2012. Improving management of Type 1 diabetes in the UK: the DAFNE programme
as a research test-bed. Principal Investigator in collaboration with Dr J Lawton, Dr
M Clarke, Ms G Thompson, Prof S Amiel, Prof M Campbell, Dr P Mansell, Dr I
Lawrence, Ms C Taylor, Ms L Oliver (Chief Investigator)
£1.8m
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Diabetes UK. Jan 2009-July 2013. KICk-OFF: A multi-centre, randomised controlled
trial comparing intensive structured education with standard education in 11-16 year
olds on intensive insulin therapy. Dr K Price, Prof C Eiser Dr J Wales, Dr J
Freeman(co-investigator)
£1.35m
Diabetes UK. April 2008-March 2012. Overnight hypoglycaemia prevention in adult
subjects with type 1 diabetes: Closing the loop with Dr R Hovorka, Prof S Amiel Dr M
Evans,
(co-investigator) £750k
Diabetes UK. Sep 2009-March 2012. Prevention of recurrent severe hypoglycaemia:
a definitive RCT comparing optimised MDI and CSII with or without adjunctive realtime continuous glucose monitoring. Hypo-COMPASS Dr J Shaw, Prof D Kerr, Dr D
Flanagan, Dr M Evans, Dr J Speight (co-investigator)
£1.4m
HTA June 2011- May 2016. The REPOSE (Relative Effectiveness of Pumps over
MDI and Structured Education) Trial. Principal Investigator in collaboration with Dr
Cindy Cooper, Professor Mike Campbell, Prof Simon Dixon, Dr Julia Lawton, Dr Kath
Barnard, Dr R Lindsay, Dr P Hammond, Prof S Amiel, Dr M Evans, Dr A Jaap, Dr F
Green.
£3.7m
Sanders DS (PI)“The influence of gluten exposure in Diabetes Mellutus” Bardhan
Research & Education trust of Rotherham 2004) £72, 460 Role: Co-applicant
Tesfaye S (PI). Central Nervous System involvement in Diabetic Neuropathy
Diabetes UK Sheffield Group (December 2008) £7500
Tesfaye (PI). Central pain processing in painful diabetic neuropathy. JDRF (2009)
$484,665
Tesfaye S (PI) Dynamic pupillometry & spectral analysis of HRV as early biomarkers
of autonomic neuropathy. National Institute of Health (US–NIDDK) (2008) $277,000
USD.
Tesfaye S. (PI) Thalamic neuronal dysfunction in diabetic neuropathy: implications for
pathogenesis and treatment”. Diabetes UK (November, 2004) £105,454
Tesfaye S (PI) “Spinal cord in Diabetic neuropathy” Diab UK (2001) £134,000
Tesfaye S (PI). “Randomised, controlled trial studying the addition of CBME to
conventional treatment in painful diabetic neuropathy”. Diabetes UK (2003) £93,563
Malik R (PI). “Pathophysiology of painful diabetic neuropathy” Diabetes UK (2003)
£80,284. Role: Co-applicant
CRUK £0.5 million TRYMS study
EUFP7 5.6 million euros, Infacort study
Diurnal Ltd £2 million chronocort studies.
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Selected publications relevant to our Experimental Medicine Work
Hypoglycaemia and Type 1 diabetes
1. Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale
M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML: Overnight
closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes:
crossover randomised controlled studies. BMJ 342:d1855, 2011
2. Kengne AP, Patel A, Marre M, Travert F, Lievre M, Zoungas S, Chalmers J, Colagiuri
S, Grobbee DE, Hamet P, Heller S, Neal B, Woodward M: Contemporary model for
cardiovascular risk prediction in people with type 2 diabetes. Eur J Cardiovasc Prev
Rehabil 2011
3. Frier BM, Schernthaner G, Heller SR: Hypoglycemia and cardiovascular risks.
Diabetes Care 34 Suppl 2:S132-7, 2011
4. Choudhary P, Lonnen K, Emery CJ, Freeman JV, McLeod KM, Heller SR:
Relationship Between Interstitial and Blood Glucose During Hypoglycemia in
Subjects with Type 2 Diabetes. Diabetes Technol Ther 2011
5. Kengne AP, Patel A, Colagiuri S, Heller S, Hamet P, Marre M, Pan CY, Zoungas S,
Grobbee DE, Neal B, Chalmers J, Woodward M: The Framingham and UK
Prospective Diabetes Study (UKPDS) risk equations do not reliably estimate the
probability of cardiovascular events in a large ethnically diverse sample of patients
with diabetes: the Action in Diabetes and Vascular Disease: Preterax and DiamicronMR Controlled Evaluation (ADVANCE) Study. Diabetologia 53:821-831, 2010
6. Choudhary P, Geddes J, Freeman JV, Emery CJ, Heller SR, Frier BM: Frequency of
biochemical hypoglycaemia in adults with Type 1 diabetes with and without impaired
awareness of hypoglycaemia: no identifiable differences using continuous glucose
monitoring. Diabet Med 27:666-672, 2010
7. Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward M, Ninomiya
T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M, Heller S: Severe
hypoglycemia and risks of vascular events and death. N Engl J Med 363:1410-1418,
2010
8. Ferrari G, L, Marques J, L B, Gandhi R, A, Heller S, R, Schneider F, K, Tesfaye S,
Gamba H, R: Using dynamic pupillometry as a simple screening tool to detect
autonomic neuropathy in patients with diabetes: a pilot study. Biomed Eng Online
9:26, 2010
9. de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai A, Cooper M,
Grobbee DE, Hackett M, Hamet P, Heller SR, Lisheng L, Macmahon S, Mancia G,
Neal B, Pan CY, Patel A, Poulter N, Travert F, Woodward M: Cognitive function and
risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes:
the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified
Release Controlled Evaluation (ADVANCE) trial. Diabetologia 2009
10. Choudhary P, Lonnen K, Emery CJ, MacDonald IA, MacLeod KM, Amiel SA, Heller
SR: Comparing hormonal and symptomatic responses to experimental
hypoglycaemia in insulin- and sulphonylurea-treated Type 2 diabetes. Diabet Med
26:665-672, 2009
11. Zoungas S, de Galan BE, Ninomiya T, Grobbee D, Hamet P, Heller S, MacMahon S,
Marre M, Neal B, Patel A, Woodward M, Chalmers J, ADVANCE Collaborative G:
Combined Effects of Routine Blood Pressure Lowering and Intensive Glucose
Control on Macrovascular and Microvascular Outcomes in Patients With Type 2
Diabetes New results from the ADVANCE trial. Diabetes Care 32:2068-2074, 2009
12. Heller SR: A summary of the ADVANCE Trial. Diabetes Care 32 Suppl 2:S357-61,
2009
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13. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service
FJ: Evaluation and management of adult hypoglycemic disorders: an Endocrine
Society Clinical Practice Guideline. J Clin Endocrinol Metab 94:709-728, 2009
14. Zoungas S, de Galan BE, Ninomiya T, Grobbee D, Hamet P, Heller S, Macmahon S,
Marre M, Neal B, Patel A, Woodward M, Chalmers J: The combined effects of routine
blood pressure lowering and intensive glucose control on macrovascular and
microvascular outcomes in patients with type 2 diabetes; new results from
ADVANCE. Diabetes Care 2009
15. Heller SR: Minimizing hypoglycemia while maintaining glycemic control in diabetes.
Diabetes 57:3177-3183, 2008
16. Heller SR: Hypoglycaemia in Type 2 diabetes. Diabetes Res Clin Pract 82 Suppl
2:S108-11, 2008
17. Munir A, Choudhary P, Harrison B, Heller S, Newell-Price J: Continuous glucose
monitoring in patients with insulinoma. Clin Endocrinol (Oxf) 68:912-918, 2008
18. Ferrari GL, Marques JL, Gandhi RA, Emery CJ, Tesfaye S, Heller SR, Schneider FK,
Gamba HR: An approach to the assessment of diabetic neuropathy based on
dynamic pupillometry. Conf Proc IEEE Eng Med Biol Soc 2007:557-560, 2007
19. Heller S, Kozlovski P, Kurtzhals P: Insulin's 85th anniversary--An enduring medical
miracle. Diabetes Res Clin Pract 78:149-158, 2007
20. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter
N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia
G, Mogensen CE, Pan CY, Rodgers A, Williams B: Effects of a fixed combination of
perindopril and indapamide on macrovascular and microvascular outcomes in
patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled
trial. Lancet 370:829-840, 2007
21. Heller SR, Nicholson AN: Aircrew and type 1 diabetes mellitus. Aviat Space
Environ Med 77:456-458, 2006
CNS imaging and diabetes, Biomarkers of diabetic autonomic neuropathy.
1. Selvarajah D, Wilkinson ID, Gandhi R, Griffiths PD, Tesfaye S. Microvascular
perfusion abnormalities of the Thalamus in painful but not painless diabetic
polyneuropathy: a clue to the pathogenesis of pain in type 1 diabetes. Diabetes Care
2011 Mar;34(3):718-20. [Epub ahead of print]
2. Kempler P, Amarenco G, Freeman R, Frontoni S, Horowitz M, Stevens M, Low P,
Pop-Busui R, Tahrani A, Tesfaye S, Várkonyi T, Ziegler D, Valensi P; on behalf of
the Toronto Consensus Panel on Diabetic Neuropathy. Gastrointestinal autonomic
neuropathy, erectile-, bladder- and sudomotor dysfunction in patients with diabetes
mellitus: clinical impact, assessment, diagnosis, and management. Diabetes Metab
Res Rev 2011 [Epub ahead of print].
3. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M,
Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P; on behalf of the Toronto
Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in
diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab
Res Rev 2011 [Epub ahead of print].
4. Tesfaye S, Vileikyte L, Rayman G, Sindrup S, Perkins B, Baconja M, Vinik A Boulton
A; on behalf of the Toronto Expert Panel on Diabetic Neuropathy Painful Diabetic
Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment
and Management. Diabetes Metab Res Rev 2011 [Epub ahead of print].
5. Bernardi L, Spallone V, Stevens M, Hilsted J, Frontoni S, Pop-Busui R, Ziegler D,
Kempler P, Freeman R, Low P, Tesfaye S, Valensi P; on behalf of the Toronto
Consensus Panel on Diabetic Neuropathy. Investigation methods for cardiac
autonomic function in human research studies. Diabetes Metab Res Rev 2011
[Epub ahead of print].
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6. Malik R, Veves A, Tesfaye S, Smith G, Cameron N, Zochodne D, Lauria G; on behalf
of the Toronto Consensus Panel on Diabetic Neuropathy. Small Fiber Neuropathy:
Role in the diagnosis of Diabetic Sensorimotor Polyneuropathy. Diabetes Metab
Res Rev 2011 [Epub ahead of print].
7. Selvarajah D, Wilkinson ID, Davies J, Gandhi R, Tesfaye S. Central nervous
system involvement in diabetic neuropathy. Curr Diab Rep. 2011;11(4):310-22.
8. Gill GV, Tekle A, Reja A, Wile D, English PJ, Diver M, Williams AJ, Tesfaye S.
Immunological and C-peptide studies of patients with diabetes in northern Ethiopia:
existence of an unusual subgroup possibly related to malnutrition. Diabetologia.
2011; 54(1):51-7.
9. Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G,
Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P on behalf of The Toronto
Diabetic Neuropathy Expert Group. Diabetic Neuropathies: Update on Definitions,
Diagnostic Criteria, Estimation of Severity and Treatments. Diabetes Care
2010;33(10):2285-93.
10. Charles M, Soedamah-Muthu SS, Tesfaye S, Fuller JH, Arezzo JC, Chaturvedi N,
Witte DR; EURODIAB Prospective Complications Study Investigators. Low peripheral
nerve conduction velocities and amplitudes are strongly related to diabetic
microvascular complications in type 1 diabetes: the EURODIAB Prospective
Complications Study. Diabetes Care 2010; 33(12):2648-53.
11. Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJ, O'Brien PC; Cl vs.
NPhys Trial Investigators, Albers JW, Andersen H, Bolton CF, England JD, Klein CJ,
Llewelyn JG, Mauermann ML, Russell JW, Singer W, Smith AG, Tesfaye S, Vella A.
Signs and symptoms versus nerve conduction studies to diagnose diabetic
sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve 2010;42(2):157-64.
12. Gandhi RA, Marques JL, Selvarajah D, Emery CJ, Tesfaye S. Painful diabetic
neuropathy is associated with greater autonomic dysfunction than painless diabetic
neuropathy. Diabetes Care. 2010 Jul;33(7):1585-90
13. Ferrari GL, Marques JL, Gandhi RA, Heller SR, Schneider FK, Tesfaye S, Gamba
HR. Using dynamic pupillometry as a simple screening tool to detect autonomic
neuropathy in patients with diabetes: a pilot study. Biomed Eng Online. 2010; 17: 926.
14. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled
double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful
diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 2010;
33(1):128-30.
15. Tesfaye S, Selvarajah D. The Eurodiab study: what has this taught us about diabetic
peripheral neuropathy? Curr Diab Rep. 2009 Dec;9(6):432-4.
16. Tesfaye S. Advances in the management of painful diabetic neuropathy. Curr Opin
Support Palliat Care. 2009;3(2):136-43
17. Elliott J, Tesfaye S, Chaturvedi N, Gandhi RA, Stevens LK, Emery C, Fuller JH; the
EURODIAB Prospective Complications Study Group. Large fibre dysfunction in
diabetic peripheral neuropathy is predicted by cardiovascular risk factors. Diabetes
Care. 2009;32(10):1896-900
18. Istenes I, Keresztes K, Hermányi Z, Putz Z, Vargha P, Gandhi R, Tesfaye S,
Kempler P. Non-invasive evaluation of neural impairment in subjects with impaired
glucose tolerance. Diabetes Care 2009;32(1):181-3.
19. Selvarajah D, Wilkinson ID, Emery CJ, Harris ND, Shaw PJ, Witte DR, Griffiths PD,
Tesfaye S. Thalamic Neuronal Dysfunction in Type 1 Patients with Diabetic
Peripheral Neuropathy. Diabetologia 2008; 51(11):2088-92.
20. Istenes I, Keresztes K, Hermányi Z, Putz Z, Vargha P, Gandhi R, Tesfaye S,
Kempler P. Relationship between autonomic neuropathy and hypertension--are we
underestimating the problem? Diabet Med 2008;25(7):863-66.
21. Soedamah-Muthu SS, Chaturvedi N, Witte DR, Stevens LK, Porta M, Fuller JH;
EURODIAB Prospective Complications Study Group. Relationship between risk
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factors and mortality in type 1 diabetic patients in Europe: the EURODIAB
Prospective Complications Study (PCS). Diabetes Care. 2008;31(7): 360-6.
22. Rubino A, Rousculp MD, Davis K, Wang J, Bastyr EJ, Tesfaye S. Diagnosis of
diabetic peripheral neuropathy among patients with type 1 and type 2 diabetes in
France, Italy, Spain, and the United Kingdom. Prim Care Diabetes 2007
Sep;1(3):129-34.
23. Moustafa M, Bullock AJ, Creagh FM, Heller S, Jeffcoate W, Game F, Amery C,
Tesfaye S, Ince Z, Haddow DB, MacNeil S. Randomized, controlled, single-blind
study on use of autologous keratinocytes on a transfer dressing to treat non-healing
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Endocrinology
1.
P G Murray, A Read, I Banerjee, A J Whatmore, L E Pritchard, R A Davies, J
Brennand, AWhite, R J Ross and P E Clayton. Reduced appetite and body mass
index with delayed puberty in a mother and son: association with a rare novel
sequence variant in the leptin gene. European Journal of Endocrinology (2011)
164 521–527
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I.K. Tailor; M. Akil; I. Rennie; R.J. Ross; J.A. Snowden Reconstitution Graves'
disease following autologous haematopoietic stem cell transplantation for severe
diffuse systemic sclerosis. QJM 2011; doi: 10.1093/qjmed/hcr050
Debono M, Sheppard L, Irving S, Jackson P, Butterworth J, Brookes ZL, NewellPrice J, Ross JJ, Ross RJ. Assessing adrenal status in patients before and
immediately after coronary artery bypass graft surgery. Eur J Endocrinol. 2011
Mar;164(3):413-9. Epub 2010 Dec 23
Perogamvros I, Owen LJ, Newell-Price J, Ray DW, Trainer PJ, Keevil BG.
Simultaneous measurement of cortisol and cortisone in human saliva using liquid
chromatography-tandem mass spectrometry: application in basal and stimulated
conditions.
Greenfield DM, Walters SJ, Coleman RE, Hancock BW, Snowden JA, Shalet SM,
DeRogatis LR, Ross RJ Quality of life, self-esteem, fatigue, and sexual function in
young men after cancer: a controlled cross-sectional study. Cancer 2010:116:15921601
Wass J, Toogood A, Brabant G, Ball S, Ross R Survivors of childhood cancer.
Integrated follow-up is needed. BMJ 2010:340:c588
Verma S, Vanryzin C, Sinaii N, Kim MS, Nieman LK, Ravindran S, Calis KA, Arlt
W, Ross RJ, Merke DP A pharmacokinetic and pharmacodynamic study of delayedand extended-release hydrocortisone (Chronocort) vs. conventional hydrocortisone
(Cortef) in the treatment of congenital adrenal hyperplasia. Clin Endocrinol (Oxf)
2010: 72:441-447
E. Ferrandis, S. L. Pradhananga, C. Touvay, C. Kinoshita, I. R. Wilkinson, K.
Stafford, Z. Wu, C. J. Strasburger, J. R. Sayers, P. J. Artymiuk and R. J. Ross.
Immunogenicity, toxicology, pharmacokinetics and pharmacodynamics of growth
hormone ligand-receptor fusions. Clin Sci (Lond) 2010:119:483-491
Arlt W, Willis DS, Wild SH, Krone N, Doherty EJ, Hahner S, Han TS, Carroll PV,
Conway GS, Rees DA, Stimson RH, Walker BR, Connell JM, Ross RJ. 2010. Health
status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J
Clin Endocrinol Metab 95:5110-5121.
Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, NewellPrice J, Darzy K, Merke DP, Arlt W, Ross RJ. Modified-release hydrocortisone to
provide circadian cortisol profiles. J Clin Endocrinol Metab 2009 May;94(5):154854. Epub 2009 Feb 17.
Debono M, Ross R, Newell-Price J 2009 Inadequacies of glucocorticoid
replacement and improvements by physiological circadian therapy. Eur J Endocrinol
2009; 160,719-29.
Miguel Debono, Cyrus Ghobadi, Amin Rostami-Hodjegan, Hiep Huatan, Michael
J Campbell, John Newell-Price, Ken Darzy, Deborah P Merke, Wiebke Arlt, and
Richard J Ross. Modified-release hydrocortisone to provide circadian cortisol
profiles. J Clin Endocrinol Metab 2009,94,1548-54.
Michel G, Greenfield DM, Absolom K, Ross RJ, Davies H, Eiser C 2009 Followup care after childhood cancer: survivors' expectations and preferences for care. Eur
J Cancer 45:1616-1623
Debono M, Price JN, Ross RJ 2009 Novel strategies for hydrocortisone
replacement. Best Pract Res Clin Endocrinol Metab 23:221-232
Munir A, Choudhary P, Harrison B, Heller S, Newell-Price J. Continuous glucose
monitoring in patients with insulinoma. Clin Endocrinol (Oxf). 2008 Jun;68(6):912-8.
Epub 2007 Dec 17.Newell-Price J, Whiteman M, Rostami-Hodjegan A, Darzy K,
Shalet S, Tucker GT, Ross RJ. Modified-release hydrocortisone for circadian therapy:
a proof-of-principle study in dexamethasone-suppressed normal volunteers.
M Whiteman, A. Rostami-Hodjegan, K. Darzy, S. Shalet, G.T. Tucker and R.J.M.
Ross. Modified-release hydrocortisone for circadian therapy: A proof of principle
study in dexamethasone-suppressed normal volunteers. Clinical Endocrinology
2008 Jan;68(1):130-5.
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Absolom K, Eiser C, Turner L, Ledger W, Ross R, Davies H, Coleman R,
Hancock B, Snowden J, Greenfield D 2008 Ovarian failure following cancer
treatment: current management and quality of life. Hum Reprod 23:2506-2512
Siyambalapitiya S, Jonsson P, Koltowska-Haggstrom M, Gaillard R, Ho K, Ross
RJ. 2008 A cross-sectional analysis of testosterone therapies in hypopituitary men on
stable pituitary hormone replacement. Clin Endocrinol (Oxf) 2008,70,907-13.
Rinomhota AS, Bulugahapitiya DU, French SJ, Caddy CM, Griffiths RW, Ross
RJ 2008 Women gain weight and fat mass despite lipectomy at abdominoplasty and
breast reduction. Eur J Endocrinol 158:349-352
Munir A, Song F, Ince P, Walters SJ, Ross R, Newell-Price J. Ineffectiveness of
rosiglitazone therapy in Nelson's syndrome. J Clin Endocrinol Metab. 2007
May;92(5):1758-63. Epub 2007 Feb 20.
Greenfield DM, Walters SJ, Coleman RE, Hancock BW, Eastell R, Davies HA,
Snowden JA, Derogatis L, Shalet SM, Ross RJ. Prevalence and Consequences of
Androgen Deficiency in Young Male Cancer Survivors in a Controlled CrossSectional Study. J Clin Endocrinol Metab. 2007 Sep;92(9):3476-82.
Debono M, Ross RJ. Doses and steroids to be used in primary and central
hypoadrenalism. Ann Endocrinol (Paris). 2007 Sep;68(4):265-7.
Absolom K, Greenfield D, Ross R, Davies H, Hancock B, Eiser C 2007
Reassurance following breast screening recall for female survivors of Hodgkin's
lymphoma. Breast (Edinburgh, Scotland) 16:590-596
Ian R.Wilkinson, Eric Ferrandis, Peter J. Artymiuk, Marc Teillot, Chantal Soulard,
Caroline Touvay, Sarbendra L. Pradhananga, Sue Justice, Zida Wu, Kin C. Leung,
Christian J. Strasburger, Jon R. Sayers, and Richard J. Ross. .A ligand-receptor
fusion of growth hormone forms a dimer and is a potent long-acting agonist. Nature
Medicine 2007, 9, 1108-1113.
Merza Z, Rostami-Hodjegan A, Memmott A, Doane A, Ibbotson V, Newell-Price
J, Tucker GT, Ross RJ. Circadian hydrocortisone infusions in patients with adrenal
insufficiency and congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2006
Jul;65(1):45-50.
Maamra M, Milward A, Esfahani HZ, Abbott LP, Metherell LA, Savage MO, Clark
AJ, Ross RJ. A 36 residues insertion in the dimerization domain of the growth
hormone receptor results in defective trafficking rather than impaired signaling. J
Endocrinol. 2006 Feb;188(2):251-61.
Kelberman D, Rizzoti K, Avilion A, Bitner-Glindzicz M, Cianfarani S, Collins J,
Chong WK, Kirk JM, Achermann JC, Ross R, Carmignac D, Lovell-Badge R,
Robinson IC, Dattani MT. Mutations within Sox2/SOX2 are associated with
abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans. J Clin
Invest. 2006 Sep;116(9):2442-55.
Fang P, Kofoed EM, Little BM, Wang X, Ross RJ, Frank SJ, Hwa V, Rosenfeld
RG. A mutant signal transducer and activator of transcription 5b, associated with
growth hormone insensitivity and insulin-like growth factor-I deficiency, cannot
function as a signal transducer or transcription factor. J Clin Endocrinol Metab.
2006 Apr;91(4):1526-34. Epub 2006 Feb 7.
Merza Z, Blumsohn A, Mah PM, Meads DM, McKenna SP, Wylie K, Eastell R,
Wu F, Ross RJ 2006 Double-blind placebo-controlled study of testosterone patch
therapy on bone turnover in men with borderline hypogonadism. Int J Androl 29:381391
Absolom K, Greenfield D, Ross R, Horne B, Davies H, Glaser A, Simpson A,
Waite H, Eiser C 2006 Predictors of clinic satisfaction among adult survivors of
childhood cancer. Eur J Cancer 42:1421-1427
Eiser C, Absolom K, Greenfield D, Glaser A, Horne B, Waite H, Urquhart T,
Wallace WH, Ross R, Davies H 2006 Follow-up after childhood cancer: Evaluation of
a three-level model. Eur J Cancer
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Greenfield DM, Wright J, Brown JE, Hancock BW, Davies HA, O'Toole L, Eiser C,
Coleman RE, Ross RJ. 2006 High incidence of late effects found in Hodgkin's
lymphoma survivors, following recall for breast cancer screening. Br J Cancer
94:469-472
Merza Z, Rostami-Hodjegan A, Memmott A, Doane A, Ibbotson V, Newell-Price
J, Tucker GT, Ross RJ. Circadian hydrocortisone infusions in patients with adrenal
insufficiency and congenital adrenal hyperplasia. Clin Endocrinol 2006, 65:45-50
Fazeli M, Zarkesh-Esfahani H, Wu Z, Maamra M, Bidlingmaier M, Pockley AG,
Watson P, Matarese G, Strasburger CJ, Ross RJ. 2006 Identification of a
monoclonal antibody against the leptin receptor that acts as an antagonist and blocks
human monocyte and T cell activation. J Immunol Methods 312:190-200
Bowles CE, Wilkinson I, Smith RA, Moir AJ, Montgomery H, Ross RJ. R 2007
Membrane reinsertion of a myristoyl-peptidyl anchored extracellular domain growth
hormone receptor. Endocrinology 148:824-830
Siyambalapitiya S, Ibbotson V, Doane A, Ghigo E, Campbell MJ, Ross RJ.
Combining growth hormone releasing hormone-arginine and synacthen testing
diminishes the cortisol response. J Clin Endocrinol Metab. 2007 Mar;92(3):853-6.
Epub 2006 Dec 27.
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