Barwon Health Research - Endocrinology and Diabetes

Endocrinology and Diabetes

The main focus of the Endocrinology and Diabetes Research team is osteoporosis, a disease affecting over one million Australians that makes bones become brittle leading to a higher risk of breaks than in normal bone.

Much of our research uses data from the Geelong Osteoporosis Study, as well as clinical data gathered through our clinical practices. Recent analyses have focused on muscle loss, frailty and the effect of diabetes on the skeleton. In collaboration with Barwon Health's Intensive Care Unit, we are also examining the impact of critical illness on skeletal health and mortality.

Our Endocrinology Clinical Trial Unit (CTU) undertakes clinical trials in disorders of bone and calcium as well as diabetes and obesity-related studies. The CTU is the Australian lead site for a study of early intervention in Paget’s disease of bone as well as studies examining new therapeutics in the management of diabetes. The CTU is national lead on the majority of its commercially sponsored clinical trials and is renowned for its start-up timelines.

Research Areas

Geelong Osteoporosis Study

The Geelong Osteoporosis Study (GOS) is an internationally recognized, large population-based longitudinal epidemiological study that initially recruited 1494 women beginning in 1994 and 1,538 men beginning in 2001 from the Commonwealth electoral rolls. Participants have been evaluated with BMD, body composition, bone turnover, glucose tolerance, serum lipids, medication exposure, medical history, alcohol and tobacco exposure, muscle strength and balance, falls history, quality of life and mental health assessments.

GOS has documented the prevalence of osteoporosis in Australia and fracture incidence as well as evidence that hip fracture rates have decreased, possibly related to increased adiposity of the population. We have examined the influence of prior fracture and socioeconomic status on fracture incidence. The interaction between socioeconomic status and risk factors for fracture has been explored. The effect of various exposures to fracture risk such as rheumatoid arthritis, paracetamol use, diabetes and impaired glucose tolerance have been reported. The GOS was among the first to report an association between selective serotonin receptor inhibitors, used in the treatment of mental illness and fragility fractures. We have explored the bone densitometric definition of osteoporosis and generated normative data for calcaneal ultrasound, bone turnover markers and lean mass. We have described the prevalence of obesity and overweight in the Australian population, how this has changed in the past decade and have examined the relationship between adiposity and bone health.

Our fracture data defined Australian population age-, gender-and BMD-specific fracture rates used extensively in preparation of the Fracture Summit Report, influenced the Prescriber Benefits Advisory Committee to approve benefits for primary fractures prevention and is the basis of the Osteoporosis Australia Burden of Disease Report the has provided an accurate assessment of the cost of fragility fractures in Australia. We contributed data to the international meta-analysis that established that Trabecular Bone Score (TBS), a bone densitometry-derived measure improves fracture prediction and have continued to explore the utility of TBS in a variety of disease states.

Currently the GOS is leading the introduction of impact miroindentation as an assessment of bone fragility using the OsteoProbe RUO (Research Use Only), developed in 2012, which measures physical properties of the tibia, the larger bone in the lower leg. We have contributed data to an international collaboration to develop reference ranges and have published data on its use to assess skeletal fragility in patients with diabetes and chronic kidney disease.

The GOS has been supported by grants from the Geelong Regional Research Foundation, The Victorian Health Promotion Foundation, Percy Baxter Charitable Trust, The University of Melbourne, Ronald Geoffrey Arnott Foundation, Merck, Sharp and Dohme Australia, NHMRC, Deakin University, Perpetual Trustees, The American Society for Bone and Mineral Research, BUPA, HCF, Barwon Health Foundation, Osteoprosis Australia and Amgen

Skeletal Outcomes Following Intensive Care (S0Fter)

Intensive care patients face health issues that extend beyond their critical illness. The current evidence indicates an association between critical illness and poor skeletal outomes. This includes increased loss of bone mineral density (BMD), increased bone turnover markers (BTMs), increased fracture risk, and an increased rate of fragility fracture compared to matched community controls. This is most pronounced in older female survivors of critical illness.

In collaboration with Assoc Prof Neil Orford, we have undertaken a randomised, placebo-controlled study to evaluate the safety of treatments that prevent bone loss in the intensive care setting. Assuming a satisfactory safety profile, we will progress to a full scale randomised multicentre study examining changes in bone mineral density in response to antifracture therapies. Funding is being sought for the multicentre study from MRFF and NHMRC.

Early intervention for Paget’s disease of bone (ZiPP study)

Paget’s disease of bone is a skeletal disorder characterised by localised increases in bone cell activity at one or more sites throughout the skeleton. Genetic factors play a key role in this disorder and the most important susceptibility gene is SQSTM1. Mutations of SQSTM1 have been detected in between 40% and 50% of people with a family history of Paget’s disease and up to 15% of those who are unaware of a family history. The Zoledronate in the Prevention of Paget’s disease (ZiPP) study is a large scale study which aims to investigate the acceptability of genetic testing for Paget’s disease, coupled with offer of targeted intervention with zoledronic acid or placebo in SQSTM1 mutation carriers. This study addresses one of the unresolved questions in the management of Paget’s disease, namely, whether early intervention can prevent or delay the onset of complications associated with this disorder.

FAME 1 Eye Study

Diabetes is the commonest cause of working-age adult-onset vision loss and current treatments are not fully effective. Recent studies proved a benefit on retinopathy progression with fenofibrate in type 2 diabetes: FIELD, ACCORD Lipid trials, but it has not been studied in type 1 diabetes. This NHMRC sponsored multicentred placebo-conntrolled clinical trial aims to at least 450 participants to evaluate the effects of once daily oral fenofibrate on clinically meaningful diabetic retinopathy progression over at least 3 years in adults with type 1diabetes and existing diabetic retinopathy.

AI assisted diagnosis of Diabetic Retinopathy

The Diabetes referral Centre was one of 2 clinical sites that contributed to a feasibility study of a novel artificial intelligence-based screening model for diabetic retinopathy in collaboration with the Centre for Eye Research Australia. The AI assisted screening as feasible and well accepted by patients. Future work will focus on the diagnostic accuracy, adherence to referral and cost effectiveness.

Sodium-Glucose Co-transporter 2 Inhibitors and Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is an emerging adverse effect of sodium glucose co-tranporter 2 inhibitors (SGKT2i), used in the treatment of type 2 diabetes. The incidence, presentation and risk factors of SGLT2i-associated DKA have not been compared to patients with type 2 diabetes who developed DKA, but were not using SGLT2i. We therefore undertook a large retrospective multi-centre controlled cohort study across all public hospitals in the cities of Melbourne and Geelong, with a combined population of 5 million.

The Environmental Determinants of Islet Autoimmunity (ENDIA) Study

We participate in the ENDIA Study, an NHMRC-funded longitudinal observational study of 1500 babies Australia-wide who have a first degree relative with type 1 diabetes. Participants include:

Pregnant women with type 1 diabetes
Men with type 1 diabetes whose partner is pregnant
Children with type 1 diabetes whose mother is pregnant
Babies under 6 months of age with a first degree relative (mum, dad, brother or sister) who has type 1 diabetes.

ENDIA researchers are investigating factors that may contribute to the development of islet autoimmunity and type 1 diabetes in children, such as:

The genes of the participating child and their family member with type 1 diabetes
The method of delivery (natural birth versus caesarean section)
The mother’s nutrition during pregnancy and breast feeding
Exposure to viruses during pregnancy and early life

Identifying the factors that initiate islet autoimmunity in early life could lead to a means of preventing type 1 diabetes before it begins. For more information visit www.endia.org.au.

Collaborating Organisations

IMPACT SRC Deakin University	Lausanne University Hospital, Switzerland	Active Life Sciences, California
Hospital del Mar-IMIM, Autonomous, University of Barcelona	University of Edinburgh, Western General Hospital	Westmead Hospital
Centre for Eye Research Australia	Monash Health	Hudson Institute of Medical Research

Research Team

Research Staff

Professor Mark Kotowicz, Director
Dr Shannon McCarthy, Clinical Trial Principal Investigator
Dr Aaron Choy, Endocrine Fellow
Dr Anna Anderson, Endocrine Fellow
Alana Sarah, Clinical Trials Unit Manager
Bree Sarah, Clinical Trials Unit Manager
Jo Chambers, Clinical Trials Nurse Coordinator
Kate Ellis, Clinical Trials Nurse Coordinator
Fahriya Zandari, Clinical Trials Nurse Coordinator

Research Students

Lelia de Abreu, PhD, Glycaemia status, all-cause mortality and skeletal morbidity in women
Monica Tembo, PhD, Biological factors that underpin frailty and musculoskeletal decline
Matthew Thackery, MPhil, The effect of critical illness on muscle mass

Research News

Research in Focus: A potential new screening tool for women at risk for progressive muscle loss

Sarcopenia is the loss of muscle mass, quality, and strength associated with ageing. It is progressive and is linked to physical disability, poor quality of life and earlier death.

Studies suggest that sarcopenia can be slowed and side effects reduced for people at risk by early interventions such as lifestyle changes or medication. This requires the early identification of people at risk of sarcopenia, however many people who could benefit are missing out due to the fact that current screening tests are complex and need to be performed by specialists.

Barwon Health and Deakin University researchers, through their work leading the world-renowned Geelong Osteoporosis Study, recognised that people at risk of osteoporosis (brittle bones) have similar risk factors to people at risk of sarcopenia. In this investigation, they used Geelong Osteoporosis Study data to test the accuracy of a simple web-based fracture risk calculator known as FRAX in identifying women at long term risk of sarcopenia.

The study showed that the FRAX calculator is likely to predict the 10-year risk for sarcopenia with high sensitivity and a high predictability. The finding that there were a number of false positives means it is unlikely to miss many who would progress to sarcopenia.

An important advantage is that the FRAX calculator identifies risk factors without the need for specialised equipment. Given that the FRAX online calculator is accessible and already used in clinical practice, there is potential for FRAX to be considered as a simple screening tool for early identification and intervention.

Click here to read the full article.

Barwon Health researchers recognised in international bone health publication

Congratulations to Barwon Health and Deakin University researchers Pamela Rufus-Membere, Kara Holloway-Kew, Mark Kotowicz and Julie Pasco, whose 2019 Endocrinology publication “Associations Between Bone Impact Microindentation and Clinical Risk Factors for Fracture” has been selected for inclusion in the 2020 Endocrine Society Bone Health Thematic Issue. This special issue is a curated collection of journal articles focused on bone health that were published in 2018–2020.

In this publication, the team establishes that risk factors for fracture are associated with poor bone impact microindentation (BMSi), a way of assessing bone hardness, and would be consistent with BMSi being a valuable for assessing fracture risk.

Described by the Society as a cutting-edge, influential contribution to the endocrine community, this selection recognises the significant impact of the team’s work on osteoporosis research across the world.

Read the original article here.
Read more about Mark Kotowicz’s research here.
Read more about Julie Pasco’s research here.

Our publications continue to lead the way

Congratulations to our research team for two recent awards recognising the impact of their publications on the worldwide research effort into improving patient outcomes.

The International Osteoporosis Foundation Award for Publishing Excellence 2019 was awarded to Kara Holloway-Kew et al for the publication: Trabecular bone score in men and women with dysglycaemia. Calcif Tissue Int 2018 Jan;102(1):32-40.
The Clinical Endocrinology (Oxford) top downloaded paper 2018-9 was ‘Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australian Menopause Society and the Clinical Oncology Society of Australia’, co-authored by Mark Kotowicz. Clin Endocrinol (Oxf) 2018: 89(3):280-296

Congratulations to our latest PhD scholars

Featured Publications

Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the endocrine society of Australia, the Australian and New Zealand Bone & Mineral Society. Grossmann M, Ramchand SK, Milat F, Vincent A, Lim E, Kotowicz MA, Hicks J, Teede H. Clin Endocrinol (Oxf). 2018;89: 280-296.

Cited By Citation in Context

Trabecular bone score in men and women with impaired fasting glucose and diabetes. [NOTE - Full text for Barwon Health staff; public can view abstract]. Holloway KL, De Abreu, Lelia L. F., Hans D, Kotowicz MA, Sajjad MA, Hyde NK, Pasco JA. Calcif Tissue Int. 2017;102: 32-40.

Cited By Citation in Context

Changes in Bone Mineral Density in the Year After Critical Illness. Orford NR, Lane SE, Bailey M, Pasco JA, Cattigan C, Elderkin T, Brennan-Olsen SL, Bellomo R, Cooper DJ, Kotowicz MA. Am J Respir Crit Care Med. 2016;193(7): 736-744.

Cited By Citation in Context

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, et al. J Bone Min Res. 2015;31: 940-948.

Cited By Citation in Context

Body mass index and measures of body fat for defining obesity and underweight: A cross-sectional, population-based study. Pasco JA, Holloway KL, Dobbins AG, Kotowicz MA, Williams LJ, Brennan SL. BMC Obesity. 2014;1:9142.

Cited By Citation in Context

Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, Woodward M, Boundy K, Ellis KA, Bush AI, et al. Diabetes Care. 2013;36: 2981-2987.

Cited By Citation in Context

Skeletal morbidity among survivors of critical illness. [NOTE - Full text for Barwon Health staff; public can view abstract]. Orford NR, Saunders K, Merriman E, Henry M, Pasco J, Stow P, Kotowicz M. Crit Care Med. 2011 Jun;39(6) 1295-1300.

Cited By Citations in Context

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. Duncan EL, Danoy P, Kemp JP, Leo PJ, McCloskey E, Nicholson GC, Eastell R, Prince RL, Eisman JA, Jones G, et al. PLoS Genetics. 2011;7(4):e1001372.

Cited By Citation in Context

Prevalence of osteoporosis in Australian men and women: Geelong Osteoporosis Study. [NOTE - Full text for Barwon Health staff; public can view abstract]. Henry MJ, Pasco JA, Nicholson GC, Kotowicz MA. Med J Aust 2011;195(6): 31-32.

Cited By Citation in Context

Annual high-dose oral vitamin D and falls and fractures in older women. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. JAMA. 2010;303: 1815-1822.

Cited By Citation in Context

Support Our Research

Participate in a Clinical Trial

To find out about clinical trials currently underway at Barwon Health, click here.

Donate

Clinical trials require ongoing investment and there are several ways to support this amazing work.

You can make a donation today and contribute to an item on our research wish list, consider a bequest in your will, or establish a lasting legacy fund in your name. No matter what size, your philanthropic support with deliver an immediate impact.

To donate now or for more information and further discuss your support, please contact the Barwon Health Foundation.

Wish List

Return economy airfare & accommodation for Dr Kara Holloway-Kew to undertake impact microindentation on 114 participants with chronic kidney disease at Westmead Hospital = $1,894
DXA scans for 228 participants with chronic kidney disease at University Hospital Geelong and Westmead Hospital= $27,360
Purchase of OsteoProbe RUO (Research Use Only) tips: 228 tips @ USD 100 per tip = $35,077

All Publications

2019

De Abreu LLF, Holloway-Kew KL, Mohebbi M, Sajjad MA, Kotowicz MA, Pasco JA. Fracture risk in women with dysglycaemia: Assessing Effects and Time-varying risk factors. Calcific Tissue Int 2019:104(3):262-72.
Pasco JA, Holloway-Kew KL, Tembo MC, Anderson K, Rufus PG, Hyde NK, Williams LJ, Kotowicz MA. Normative Data for Lean Mass Using FNIH Criteria in an Australian Setting. Calcif Tissue Int 2019:104(4):475-9
Holloway-Kew KL, de Abreu LLF, Kotowicz MA, Sajjad MA, Pasco JA. Bone Turnover Markers in Men and Women with Impaired Fasting Glucose and Diabetes. Calcif Tissue Int 2019:104(6):559-604.
Sajjad MA, Holloway KL, Mohebbi M, Kotowicz MA, Pedler D, de Abreu LFF, Livingston PM, Khasraw M, Hakkennes S, Dunning TL, Brumby S, Page RS, Sutherland A, Venkatesh S, Williams LJ, Brennan-Olsen S, Pasco JA. Association between area-level socio-demographic indicators and diabetes-related hospitalisations: A cross-sectional analysis of data from western Victoria (Australia). BMJ Open 2019: 9(5):e026880.
Mudiyanselage SB, Stevens J, Watts JW, Tascane J, Lane S, Kotowicz MA, Hayles R. Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial. J Telemed Telecare 2019:25(6):343-52.
Brennan-Olsen SL, Vogrin S, Graves S, Holloway-Kew KL, Page RS, Sajjad MA, Kotowicz MA, Livingston PM, Khasraw M, Hakkennes S, Dunning TL, Brumby S, Sutherland AG, Talevski J, Green D, Kelly TL, Williams LJ, Pasco JA. Revision joint replacement surgeries of the hip and knee across geographic region and socioeconomic status in the western region of Victoria: a cross-sectional multilevel analysis of registry data. BMC Musculoskelet Disord. 2019;20(1):300.
Anderson KB, Holloway KL, Hans D, Kotowicz MA, Hyde NK, Pasco JA. Reference Ranges for Trabecular Bone Score in Australian Men and Women. JBMR Plus 2019;3(6):e10133.
Hamblin SB, Wong R, Ekinci EI, Sah S, Jones AR, Hare MJ, Fourlanos S, George EM, Giri R, Kotowicz MA, Kyi M, LaFontaine N, MacIsaac R, Nolan BJ, O’Neal DN, Renouf D, Varadarajan S, Wong J, Xu S, Bach LA. Sodium-Glucose Co-transporter 2 Inhibitors and Diabetic Ketoacidosis: A Retrospective Controlled Cohort Study. J Clin Endocrinol Metab 2019: 104(8):3077-3087.
Grossmann M, Sabashini Ramchand S, Milat F, Amanda Vincent A, Lim E, Kotowicz MA, Hicks J, Teede H. Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Summary Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia. Med J Aust 2019: Sep;211(5):224-229.
Rufus-Membere P, Holloway-Kew KL, Diez-Perez A, Kotowicz MA, Pasco JA. Associations between bone impact microindentation and clinical risk factors for fracture. Endocrinology 2019: 160(9):2143-2150.
de Abreu LLF, Holloway KL, Sajjad MA, Kotowicz MA, Pasco JA. FRAX (Aus) Scores in Women with Impaired Fasting Glucose and Diabetes. Bone Rep 2019: 11:100223.
Cronin O, Forsyth L, Goodman K, Lewis S, Keerie C, Walker A, Porteous M, Cetnarskyj R, Lakshminarayan R, Selby S, Hampson G, Chandra R, Ho S, Tobias J, Young Min S, McKenna M, Crowley R, Fraser WD, Gennari L, Nuti R, Brandi M-L, del Pino-Montes J, Devogelaer J-P, Durnez A, Isaia G, Di Stefano M, Guanabens N, Seibel M, Walsh J, Kotowicz MA, Nicholson GC, Duncan E, Major G, Cundy T, Gilchris N, Ralston SH. Zoledronate in the prevention of Paget’s (ZiPP trial): Study protocol for a randomised trial of genetic testing and targeted Zoledronic acid therapy to prevent SQSTM1-mediated Paget’s Disease. BMJ Open 2019: 9(9):e030689.
Cowdery SP, Sajjad MA, Holloway-Kew KL, Mohebbi M, Kotowicz MA, Livingston PM, Khasraw M, Hakkennes S, Dunning TL, Brumby S, Page RS, Sutherland A, Venkatesh S, Brennan-Olsen SL, Berk M, Campbell M, Williams LJ, Pasco JA. Mapping Cancer Incidence Across Western Victoria: The Association with Age, Accessibility, and Socioeconomic Status Among Men and Women. BMC Cancer 2019: 19(1):892.
Holloway-Kew, KL, Zhang Y, Betson AG, Anderson KB, Hans D, Hyde NK, Nicholson GC, Pocock NA, Kotowicz MA, Pasco JA. How Well Does the FRAX (Aus) Calculator Predict Incident Fractures? Data from the Geelong Osteoporosis Study. Osteoporos Int 2019;30(10):2129-39.
Holloway KL, Marijanovic M, de Abreu LLF, Pasco JA, Kotowicz MA. Bone mineral density in diabetes and impaired fasting glucose. Osteoporos Int 2019;30(9):1799-1806

Last Modified: Tuesday, 22 March 2022

Research Lead

Mark Kotowicz -small-2.jpg

Professor Mark Kotowicz

Director, Department of Endocrinology and Diabetes

Phone (03) 4215 1142

Bree Sarah photo

Ms Bree Sarah

Clinical Trials Unit Manager

[email protected]

Phone (03) 4215 2875

University Hospital Geelong
Bellerine St, Geelong 3220