Research programs

Although the mechanism is far from completely understood, hyperglycaemia is ultimately responsible for much of the pathogenesis of diabetic complications. Therefore considerable research effort is devoted to understanding how best to detect and control this metabolic abnormality as early as possible. Research conducted at Sydney Medical School has shown that in a significant number of young patients there is an interesting overlap of clinical features of type 1 and type 2 diabetes. Further analysis revealed a central role played by obesity in promoting the tendency to develop this type of diabetes earlier and earlier in our society. This is a great public health concern due to the increasing prevalence of obesity in adolescents. The Foundation supported a major multinational study (The DREAM Study) investigating how best to prevent progression of prediabetes to overt diabetes. The inter-disciplinary model of care used at the Diabetes Centre of Royal Prince Alfred Hospital has been shown in research studies to be the most effective way of providing optimal care to people with diabetes and its associated complications.

Diabetes is the commonest cause of lower limb amputation. Each year in Australia, it is estimated that 3000 people with diabetes will lose a limb. This is not only associated with increased mortality but also a great loss in quality of life. Research into diabetic foot disease is notoriously difficult and compared with other areas of diabetes research, a dearth of scientific data exists. Researchers at Sydney Medical School have developed a program systematically examining several interacting aspects of diabetic foot disease. These include studies of wound healing, bacterial infection, neuropathy and microvascular disease, all important pathogenic factors of amputation. This model allows wound tissue to be obtained for studying chemical composition, tensile strength, growth factor concentration and angiogenesis.

One of the great difficulties of managing diabetic foot disease is recognition and treatment of infection, both traditionally dependent on subjective clinical criteria. A novel method of quantitating bacterial content in a diabetic wound was developed and it showed bacterial count to correlate strongly with wound healing. This study could lead to a much needed objective indicator for antibiotic treatment of diabetic foot ulcers.

Many people with diabetes suffer from distressing pain in the feet due to sensory neuropathy, for which treatment is unsatisfactory and understanding of its pathogenesis poor. To explore this area, researchers used a novel technique of biopsying skin at the lower extremities to quantitate cutaneous small nerve fibres which are responsible for transmitting the pain sensation. It was shown in many individuals with painful neuropathy that there was a severe loss of these small nerve fibres, giving a strong clue to the pathogenesis of this important diabetic complication. Using a novel technique of laser Doppler velocimetry, researchers were able to show a link between the microvasculature and the function of these small nerve fibres, opening an important avenue of further research into the pathogenesis of painful diabetic neuropathy. Magnetic Resonance Spectroscopy has also been used to identify important chemical changes in various regions of the brain which receive and process pain sensation.

Studies using the Laser Doppler technique have also revealed an important relationship between microvascular dysfunction and diabetic eye disease. This will allow researchers to focus on screening for diabetic retinopathy in high risk individuals. An ongoing research program is studying monocytes, a special type of blood cells in the circulation, to see if their surface markers and receptors could explain why some individuals are more susceptible to diabetic eye disease. Identifying monocyte subtypes may allow researchers to predict which individuals are more likely to develop microvascular complications and therefore should be targeted for intensive preventive treatment. Studies are also underway on mitochondrial DNA in diabetic individuals with different clinical profiles. Thus far it has been demonstrated that individuals with diabetic complications have an abnormal quantity of mitochondrial DNA. As mitochondria play a pivotal role in cellular metabolism, findings point to an important pathogenic mechanism in the development of diabetic complications.

Cardiovascular and renal diseases are major complications of diabetes and responsible for much of its excess mortality, hence, major programs of research are designed to examine various aspects of these complications. In collaboration with cardiology colleagues, the specialized technique of echocardiography with tissue Doppler measurement was used to study cardiac muscle changes. This revealed the presence of impaired cardiac muscle relaxation in many people even at a stage when heart failure or other diabetic complications are not clinically evident. The changes identified in cardiac muscle paralleled the development of microvascular abnormalities, pointing to an important aetiological link. This early manifestation of diabetic cardiomyopathy is vitally important because diastolic dysfunction is responsible for many cases of cardiac failure in people with diabetes. Additionally, to explore the unfortunate relationship between sudden death and cardiac arrhythmia in diabetes, cardiac conduction abnormalities are being examined by family studies and by continuous monitoring of glucose level and cardiac rhythm. Also at a clinical level, a study of renal function in people with diabetes who have been followed up for many years in the Diabetes Centre has provided important information to assist decision making concerning which patients can be safely treated with a combination of angiotensin converting enzyme inhibitor and angiotensin receptor antagonist without causing renal impairment.

Laboratory research at Sydney Medical School also addresses diabetes complications and cell based studies, examining in diabetes, how scar tissue (fibrosis) develops in some tissues and excess inflammation in others. Areas under study include diabetic cardiomyopathy and diabetic kidney disease, wound healing in diabetes and fatty liver with inflammation leading to liver fibrosis. Related studies are examining how fat cells develop and differentiate and respond to insulin in the body.

The Endocrinology and Diabetes Research Foundation was instrumental in providing infrastructure required to enable scientists, doctors and other health professionals at the Sydney Medical School and Royal Prince Alfred Hospital to conduct research. This program of research in preventing diabetes and its complications is well coordinated and world class in quality. It would not have been possible for the Foundation to support these activities without also the support of funding bodies including the NHMRC, Diabetes Australia Research Trust, Rebecca Cooper Foundation, Juvenile Diabetes Research Foundation International, NSW Ladies Bowl for Others Association, clinicians of Royal Prince Alfred Hospital and many other donors.