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Research

Institute of Endocrinology and Diabetes

Clinical Research

Group Leader
Clinical Associate Professor Chris Cowell Phone: 02 98453200 Email: chrisc@chw.edu.au

Current research program

The Institute of Endocrinology and Diabetes is the leading clinical paediatric endocrinology research centre in Australia. In the last 2.5 years, it has attracted approximately $4.5 million in competitive research funds and published 68 peer reviewed articles.

The key theme of our research is prevention. Our ultimate objectives are:

  • to prevent the onset of Type 1 and Type 2 diabetes in children,
  • to prevent the development of diabetes complications, and
  • to prevent the morbidity (bone pain, fractures) in children with primary and secondary osteopenia.

Our key research programs are:

Prevention of Type 1 Diabetes and its complications

  • Epidemiology of type 1 diabetes in Australia. We are leading these multicentre collaborative studies examining disease trends in children and adolescents with type 1 diabetes. Type 1 diabetes incidence in Australia is increasing approximately 2.7%/year. Our research aims to identify epidemiological factors that improve our understanding of the triggers of diabetes.
  • VIGR study: Viral etiology of Type 1 diabetes - research is being undertaken on how viruses infect and damage beta cells to trigger the onset of diabetes, with the ultimate aim being to develop vaccines to prevent diabetes. We are also studying other risk factors that may trigger diabetes, including vitamin D deficiency and dietary factors.
  • Prevention trials (TRIGR and others) - the effect of interventions (reduced exposure to cow's milk in the first 8 months of life and intranasal insulin in high risk individuals) are being studied in international randomised controlled trials
  • Prevention: we are involved in national and international collaborative multiplex and family studies aimed at further our understanding of the genetic contribution to type 1 and 2 diabetes (TrialNET and ACCDR). We are also involved in studies aimed at identifying individuals who are on the pathway to developing diabetes ('pre-diabetes') who may be eligible for intervention trials that may prevent diabetes. We are embarking on an international collaborative trial of intranasal insulin to prevent type 1 diabetes in children with prediabetes (INIT 11)
  • Genetics of diabetes complications - one of the largest global databases (cross sectional and longitudinal) of the eye, kidney and neurological complications of diabetes has been and is prospectively collected. The effect of gene variations on frequency and severity of complications is under study. We are studying the functional mechanisms by culturing white cells from adolescents with known genotype and complication phenotype; and examining their expression of antioxidant enzymes.
  • Vascular changes and soft tissue thickening in early diabetes complications, and their relationship to subsequent more severe complications. This is in collaboration with 2 investigators at the University of Melbourne.
  • International study to reduce the development of kidney abnormalities in adolescents with type 1 diabetes (in collaboration with UK and Canada)
  • Changes in lung function and heart rate variability in diabetes (in collaboration with the Respiratory Department and University School of Pharmacy)

Prevention of type 2 diabetes and insulin resistance associated with obesity

  • Longitudinal population based study at Nepean, examining environmental determinants of obesity, metabolic syndrome and cardiovascular risk
  • Intervention studies in individuals with insulin resistance syndrome - we are leading randomised controlled trials on 1) the effects of modified carbohydrate intake and 2) the effect of whole body vibration platforms on insulin sensitivity
  • The inflammatory role of visceral and subcutaneous fat in obesity is being studied using molecular techniques
  • The evolution of insulin resistance in daughters of mothers with polycystic ovary syndrome
  • Epidemiology of type 2 diabetes in NSW and Australia. We are leading population based studies determining the incidence and risk factors associated with development of type 2 diabetes in youth.

Bone health

The major areas of bone research are:

  • The natural history of osteopenic disorders
  • Prevention and treatment of primary and secondary osteoporosis.
  • Prevention and treatment of simple vitamin D deficiency
  • Exercise and bone health in children

Specific areas of interest include:

  • Natural history data of osteopenic disorders
    • Cerebral palsy
    • Neurofibromatosis type 1
    • Duchene muscular dystrophy
  • Prevention and treatment of primary and secondary osteoporosis.
    • Intravenous bisphosphonate therapy in established osteoporosis
    • Oral bisphosphonate therapy in milder forms of primary osteopenia
    • Whole body vibration training in osteogenesis imperfecta, cerebral palsy, cystic fibrosis and other causes of secondary osteopenia
  • Prevention and treatment of simple vitamin D deficiency
    • Incidence of simple vitamin D deficiency in Australia
    • Stoss therapy for simple vitamin D deficiency
  • Exercise and bone health in children
    • Effect of exercise on bone of children undertaking various sporting activities
    • Effect of whole body vibration training on bone mass and muscle function in school children

Clinical studies

In addition, there is active research addressing important clinical issues in diabetes and endocrinology with the objective of providing better outcomes and quality of life for the individual.

  • Insulin pump therapy and impact on quality of life and diabetes control; studies are focussing on impacts of new diabetes therapies, including insulin pump therapy, continuous glucose monitoring and multiple daily injection therapies.
  • Innovative studies on cortisol secretion in individuals at risk of adrenal insufficiency particularly those with other pituitary deficiencies

Major achievements in last 10 years

1) Diabetes epidemiology/aetiology leading to intervention studies
The NSW/ACT type 1 diabetes register was established in 1990. We were the first to report a rising incidence of diabetes in NSW and have led collaborative studies of diabetes incidence in Victoria and throughout Australia. Our prospectively collected incidence data form an essential source of case ascertainment for the National Diabetes Register (at the AIHW). Our research has focused on the viral aetiology of type 1 diabetes in patients at the onset of type 1 diabetes and also in the pre-diabetes period. We are now studying the effects of viral isolates on the pancreatic beta cells in vitro to understand how viruses damage the cells and affect insulin production. This research has laid the groundwork for vaccine development to prevent type 1 diabetes and for randomised controlled studies to prevent diabetes using alternate strategies.

2) Diabetes complications
The diabetes complications research group has made major contributions to our understanding of the pathogenesis of diabetes complications. Our landmark papers have demonstrated the importance of prepubertal diabetes duration in the development of complications, an effect that continues even into adulthood (ref 118). We have identified genetic polymorphisms associated with decline in nerve function and now have a partnership with a pharmaceutical company exploring therapeutic interventions using pharmacogenomics to decrease neuropathy.

Novel predictors of subsequent microvascular disease at 2-12 years follow up have been identified: namely plantar fascia thickness as an index of tissue glycation and small pupillary size as a measure of the sympathetic nervous system (refs 3, 29). More recently we have identified higher blood pressure contributes to retinopathy development independently of any renal effect. (ref 4, BMJ in press). This will result in a more aggressive approach to the treatment of blood pressure in diabetes during adolescence. Our findings have changed the way paediatricians manage diabetes and in an April issue of Archives Diseases of Childhood, a paediatrician has included 3 of our publications has having most influence on their practice.

3) The Nepean Study
an ongoing longitudinal study of children born at Nepean Hospital 1989/90 investigating environmental determinants of obesity, metabolic syndrome and cardiovascular risk. In just over a decade data has been collected four times, when the children were 9, 13, 15, 17 years. Identifying risk factors for metabolic complications, especially abdominal obesity, in young people has formed the basis of our current RCTs in management of inulin resistance and pre-diabetes. In addition data from the Nepean study has been included in two published systematic reviews (Huxley R et al Lancet 2002; 360:659; Huxley R et al JAMA 2004; 292:2755) and is included in the, NSW Health funded, Childhood Obesity Pooling Project, Australasian Child and Adolescent Obesity Research Network.

4) Understanding of normal bone development and its applications for primary and secondary osteoporosis
We have led nationally and internationally the development of normal databases for bone mass and body composition using dual energy xray absorptiometry (3 publications, 430 citations) and have demonstrated 1) the strengths and limitations of this technique via studies using comparative biology and MRI 2) the importance of lean tissue mass in bone strength and 3) the role of hormones in body composition and bone strength. On this background and with introduction of new technologies, our expertise enables us to address key issues in secondary osteoporosis in children especially immobilisation and systemic disease related bone disorders and in association with David Little, Orthopaedics, focal disorders of bone. We are international leaders in understanding the benefits and side effects of bisphosphonate therapy in children. We are now setting up a series of randomised controlled studies evaluating the role of vibration platforms on immobilisation osteoporosis.

Key publications with comments on their significance

Lu PW, Cowell CT, LLoyd-Jones SA, Briody JN, Howman-Giles R. Volumetric bone mineral density in normal subjects, aged 5-27 years. J Clin Endocrinol Metab 1996; 81(4):1586-1590. IF 6.02 Citations 178

Significance First study internationally to clearly demonstrate that calculated volumetric bone density does not significantly change during growth at hip and femur and only increases slightly at the spine during puberty. This study changed the dogma that bone density increases during growth, a belief that had arisen because of limitation of the areal technique used to measure bone density. It has led to a variety of techniques to be used to assess bone strength in children, including from our group and international leadership.

Craig ME, Howard NJH, Silink M, Rawlinson WD: Enterovirus RNA is associated with a redced frequency of HLA DRB1*03-DQB1*02 in children with type 1 diabetes. Journal of Infectious Diseases;187(10):1562-1570, 2003 Impact factor 5.363, Citations 17
Significance: Largest study to demonstrate an association between enterovirus infection and type 1 diabetes; first to show the association is strongest in patients with low risk HLA genotypes. Has led to current NHMRC project grant.

Strippoli GFM, Craig ME, Schena FP, Craig JC. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review British Medical Journal, doi:10.1126/bmj.38237.585000.7C, 2004 Impact factor 9.245, Citations 105
Significance: Major Cochrane systematic review (Dr Craig was co-author) to demonstrate outcomes of antihypertensive therapy in diabetic nephropathy, highly cited.

Gallego PH, Craig ME, Hing SJ, Donaghue KC. The Role of Blood Pressure in the development of Early Retinopathy in Adolescents with Type 1 Diabetes: A Prospective Cohort Study accepted British Medical Journal April 14, 2008 Impact factor 9.245,
Significance: Shows the continuous effect of higher blood pressure predicting retinopathy independent of renal disease. This will result in a more aggressive approach to blood pressure management in diabetes during adolescence

Donaghue KC, Fairchild JM, Craig ME, Chan AK, Hing S, Cutler LR, Howard NJ, Silink M. Do all prepubertal years of diabetes duration contribute equally to diabetes complications? Diabetes Care, 26(4):1224-9, 2003. Impact Factor 7.912, Citations 41
Significance: this has resulted in Paediatricians aiming for better glycaemic control during childhood, which was not an aim prior to this publication.

Thamotharampillai K. Chan AK. Bennetts B. Craig ME. Cusumano J. Silink M. Oates PJ. Donaghue KC. Decline in neurophysiological function after 7 years in an adolescent diabetic cohort and the role of aldose reductase gene polymorphisms. Diabetes Care 2006; 29(9):2053-7 Impact Factor 7.912 Citations 4
Significance: Longitudinal study showing decline in nerve function which is influenced by genotyping. This will lead to the possibility of using pharmacogenomics to reduce the risk of diabetic neuropathy

SP Garnett, LA Baur, CT Cowell. Waist to height ratio: a simple option for determining excess central adiposity in young people. Int J Obesity. 15th April 2008 (Impact factor 4.48)
Significance: First Australian study to demonstrate the relation between the waist to height ratio and metabolic outcomes in contemporary children. The study supports the idea of 'keeping your waist to less than half your height' which we anticipate will be adopted as a simple public health and clinical message for children and adults

S Srinivasan, GR Ambler, LA Baur, SP Garnett, M Tepsa, F Yap, GM Ward, CT Cowell. Randomized controlled trial of metformin for obesity and insulin resistance in children and adolescents - improvement in body composition and fasting insulin. J Clin Endocrinol Metab. 2006;91:2074-80 Impact factor 6.02; citations 14
Significance: One of four studies demonstrating the beneficial effect of metformin which has led to its regular use in the management of these patients

Research Staff

Senior medical research staff

  • Dr Chris Cowell MB FRCP (C) FRACP. Acting/Director Research, CHW, Director, Institute of Endocrinology & Diabetes Clinical Assoc Professor (USyd)
  • Dr Kim Donaghue MB BS PhD FRACP Head of Diabetes Services, Head of Diabetes Complications Assessment Service, Conjoint Assoc Professor (USyd)
  • Dr Geoffrey R Ambler MBBS, MD, FRACP Head of Clinical Information and Systems, Clinical Assoc Prof (USyd)
  • Dr Neville J Howard MB BS FRCP(C) FRACP Investigator, TRIGR (Australia)
  • Dr Maria Craig MBBS, PhD, FRACP, MMedSc (ClinEpid), NHMRC Practitioner Fellowship Conjoint Senior Lecturer (U Syd)
  • Dr Martin Silink AM, MD FRACP, Professor (U Syd)
  • Dr Craig Munns MBBS, PhD, FRACP Conjoint Senior Lecturer (U Syd)
  • Dr Shubha Srinivasan, MBBS, PhD, FRACP
  • Dr Ann Maguire, MBBS, FRACP

Research Fellows

  • Dr Sarah Garnett BSc M Nutr Diet PhD NHMRC Clinical Research Fellow
  • Dr Kim Ramjan BSc, MBCHB, DCH Research fellow
  • Dr Patricia Gallego BSc, MD, MSc Research fellow
  • Dr Jesper Johannesen MD DmSc Research fellow
  • Dr Paul Benitez-Aguirre BSc, MBBS, DCH Research fellow
  • Dr Myra Poon, MB BS, Research Fellow

Research Officers and Research Assistants

  • Jim Minchenko BSc (Hons) PhDSc (Med) Research Scientist, Endocrine Laboratory
  • Charmaine Tam BAppSc PhD candidate
  • Alison Pryke DipAppSc (Orth) Research Assistant, Diabetes Complications & Assessment
  • Ros Bongiorno BAppSc TRIGR Nutrition Coordinator
  • Glenda Fraser CNC TRIGR Nurse Coordinator
  • Janine Cusumano CNS Diabetes Complications & Assessment Co-ordinator
  • Margaret Lloyd CNC Diabetes Prevention Research Nurse Co-ordinator
  • Lynne Foxall RN Research Trial Co-ordinator
  • Lori Hopley, B Nutrition and Dietetics, Research Assistant

Clinical research and support staff

  • Rachel Hayes BSc (Hons) Master of Nutrition and Dietetics
  • Catherine Kay MN MBA AFACHSE Business Manager
  • Albert Chan BSc, MAppStat, Grad Dip IT, Clinical Info and Systems Manager/Statistician
  • Jenny Lee BAppSc Manager, Endocrine Laboratory
  • Oksana Markovych BAppSc Scientist, Endocrine Laboratory
  • Darna Bradford BSc Scientist, Endocrine Laboratory
  • Liz Lawrie CNC Endo-testing Unit
  • Kelly Winning RN Endo-testing Unit
  • Mary Maquade CNC Bone Services Nurse Co-ordinator
  • Nuala Harkin RSCN, RGN, CDE, NP

Research support (2005-2008)

43 project grants over 3.5 years totalling ($6.7M)
Y2005 $1.2M
Y2006 $1.4 M
Y2007 $2.1 M
Y2008 $2 M

  • NHMRC/ARC (n=5) = $3.3M
  • Other Government competitive funds (n=3) = $1M
  • Government non-competitive fund (n=7) = $1M
  • Funds from industry (n=11) = $250K
  • Other competitive fund (n=9) = $1.1M
  • Other non-competitive fund (n=1) = $100K

Opportunities for Students

Postgraduate Research available at the University of Sydney

This document was updated on Wednesday, 30 July 2008

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