Singapore, May 14, 2010: At Garvan Institute of Medical Research, Sydney, Australia, Prof Lesley Campbell, Professor of Medicine, Director of Diabetes Services, St Vincent’s Hospital said her major interest is clinical research and the focus has been in the cause of Type 2 diabetes, particularly what triggers the insulin resistance and obesity which occurs in 90% of people with Type 2 diabetes.

To study the cause without the confounding influence of hyperglycaemia or dyslipidaemia, she studies healthy close relatives of people with Type 2 diabetes— because the disease is under strong genetic influence. So far her institute has published that such people— with a high probability of developing diabetes later in life—show deficiency in a satiety hormone response called Peptide YY (PYY)—while they are still normal weight— which may predispose them to gain weight in later life.

“We also see that they have a defect in turning on fat oxidation in response to a fat meal, which may cause the later metabolic abnormalities,” she says. “Our work shows that the people who are to get diabetes already have a biological predisposition to weight gain (not just “willful overeating” as is so often said) and in blood and tissue samples we are now able to isolate the mechanisms for the earliest changes contributing to the insulin resistance which characterizes the primary defect of Type 2 diabetes (as opposed to Type 1 diabetes).”

Another area of research for Garvan Institute has been to examine the challenge of the “orphan” disease Prader Willi Syndrome (PWS): the most common nown genetic obesity disorder, due to an imprinting defect on chromosome 15. A project to examine the intense, uncontrolled hunger which disrupts the life of the family and the sufferer of this developmental disorder, sometimes resulting in PWS sufferers needing to live in care situations to restrain their eating. “We have examined the satiety and hunger hormones of volunteer subjects from the Royal Prince Alfred PWS clinic in a very strongly matched way with obese subjects without PWS to tease out any real differences intrinsic to PWS. We have found higher immune activation which may be an intrinsic part of the disease but, if anything, higher satiety hormone levels. We have completed a single dose pilot study of a novel therapeutic agent which is already released for diabetes and may be a potential treatment for PWS against appetite, as no medication is recognized as effective at present. This indicates a longer trial should follow. We are also examining the contributors to the increased cardiovascular risk in PWS subjects and are comparing the risk factors with matched obese and lean volunteers. In collaboration with Prof Herbert Herzog, also from the Garvan Institute, have commenced a study producing a mouse model of the disorder (which has only recently been possible) allowing study of the brain with knockout of the gene and study of the phenoType.”

Garvan has submitted an IVUS study of rosiglitazone post stenting examining one year results in the coronary arteries of diabetic subjects having stents in another artery. Rosiglitazone has shown improved glycaemic control, lessened inflammation including adiponectin.

Dr Reddy’s Pharma, one of India’s top pharmaceutical companies by revenues and sales, announced successful phase III results from its Balaglitazone in January 2010. Dr Reddy’s said pre-clinical studies indicated that besides robust glucose lowering ability, balaglitazone results in lower body fluid accumulation, lower fat accumulation, less heart enlargement and no reduction of bone formation, indicating that Balaglitazone may be able to displace the balance between desired and side effects, and thus show a better safety profile than full agonists of PPAR-gamma.

Danish diabetes giant Novo Nordisk has two new generation insulin products, Degludec and Degludec- Plus— that are intended to be even longer acting to improve treatment outcomes and provide more convenient insulin therapy with a possibility of fewer injections. Currently in phase III development, the Degludec and DegludecPlus development programs will involve more than 10,000 patients from 39 countries around the world.

The trial program for Degludec is known as BEGIN and will involve more than 7,000 patients. Degludec has so far demonstrated an ultra-long duration of action of more than 24hours, offering the potential of greater dosing flexibility and lower risk of hypoglycaemia. The trial program for DegludecPlus is called BOOST and will recruit over 3,000 patients. DegludecPlus is the first soluble combination of an ultralong-acting basal insulin with a boost of rapid-acting insulin (NovoRapid).

Novo Nordisk is also focusing on the development of oral protein formulations for both insulin and GLP-1 for the treatment of diabetes. Since data from Drug Abuse Warning Network (DAWN) database and elsewhere show that injections continue to be a barrier to insulin initiation among physicians treating diabetes, Novo Nordisk believes that the introduction of a safe and effective oral insulin (and GLP-1) product to the market could lead to earlier use of insulin in diabetes treatment, and hence, the potential for better treatment outcomes and reduced risk of disease-related complications in people with diabetes all over the world.

In an interview with BioSpectrum, Jesper Hoiland, Novo Nordisk’s Senior Vice-President (International Operations) said a oral insulin pill was introduced in Germany early December 2009 and is in a phase I clinical trials. “In the long run, it will be eight to ten years before you could see diabetes pill becoming available in the markets.” According to him the oral insulin looks fine in clinical trials done so far.

The power of prevention

Prof Leslie of Garvan Institute says no prevention trial of Type 1 is yet known to be successful. Insulin therapy in Type 1 has been improved by insulin analogues, usually treated with background dept insulin and short-acting analogue with each meal, but young people in particular are using insulin pump therapy. Continuous glucose monitoring is not commonly used but available in some forms, even in real time but does not yet feed to the pump via an algorithm. Transplants are offered only to those with complications, example renal failure or severe hypoglycemia. For many people, Type 2 diabetes can be managed or prevented by a healthy diet and regular exercise. Many people worldwide do not know they have diabetes, and many of those who do know are in poor control of their diabetes. Lifestyle change is still the first option for treatment for Type 2 diabetes, experts say treating diabetes early and well not only improves quality of life, but is cost-effective, especially if it prevents hospitalization. There is now conclusive evidence that good control of blood glucose levels can substantially reduce the risk of developing complications and slow their progression in all Types of diabetes.