Clinical Diabetes, Appetite and Metabolism

Our Lab is focused on the challenge of modern times: that evolution has left many of us with good survival genes which make us prone to gain weight easily and develop type 2 diabetes in times of plenty.

Our recent discoveries have been that healthy relatives of people with type 2 diabetes probably carry genes for obesity (explaining why so many have weight problems). Possible pathophysiological precursors have been detected in otherwise healthy at risk subjects from our detailed studies.  Our lab has optimised human muscle biopsies through the addition of an ice-cold saline lavage. This minimises manipulation of the sample, washes off excess blood, and avoids excessive warming of the sample by exposure to room air. We also published our study showing that when asked to overeat for one month, within days the healthy relatives of people with type 2 diabetes had gained more weight than those who didn’t have diabetic relatives, although both groups were treated identically. 

On the flipside, we have identified a group of overweight and obese humans who appear to be at lower risk of diabetes and heart disease than other obese individuals. A major focus of our laboratory is to establish the factors that confer this metabolic protection and to devise a set of clinical criteria that will assist in their identification in clinical practice. The outcome of this research will expand our knowledge regarding the relative importance of metabolic abnormalities, such as abdominal and liver fat, on the development of insulin resistance and diabetes. We will find out what protects the overweight and obese people and whether they remain at lower risk of metabolic disease over long periods of time.

Another focus of our group is the identification of specific genetic defects that cause diabetes and obesity in humans. The conditions we are studying are monogenic or single-gene obesity disorders (including melanocortin 4 deficiency), lipodystrophies (partial and generalised) and monogenic diabetes (previously known as MODY – Maturity Onset Diabetes of the Young). Major improvement in insulin resistance after bariatric surgery in a lipodystrophy due to a novel gene has just been reported for the first time.

Along these lines, an important area we have looked at with the Neuroscience Division and the Prader Willi Syndrome (PWS) Clinic at Royal Prince Alfred Hospital has been the difficult paradox of PWS: a genetic cause of relentless appetite from early childhood in a child who is initially born as a floppy baby who feeds poorly. We have described some of the abnormalities and have tested a possible treatment to help the desperate families. This has now been put into randomised trial in USA. We are hoping to test a new diabetes drug to help in the search for effective treatments in the coming year to help families with this major challenge.

Other studies have established the effects of glutamine, an amino acid, on metabolism, both in isolation and in combination with a new diabetes medication. Glutamine appears to have a promising effect on glucose lowering in the post-meal state and may offer a simple, novel and effective treatment in type 2 diabetes. We are studying the effects on an alkaline diet on insulin sensitivity in humans, to determine whether there is any scientific evidence that this approach improves metabolic health.

We have undertaken collaborative studies with the Department of Clinical Pharmacology at St Vincent’s Hospital to study the effects of metformin, particularly in relation to specific genetic variations in humans.

Our work continues the careful clinical phenotyping of disease or pre-disease states with a search for biomarkers or genetic insights into causation. Collaboration with the University of Sydney’s Brain and Mind Institute and with our own Psychiatric services has extended the possible scope of the studies for the future.

In the News

Spanning research and the clinic: top diabetes awards for Garvan leaders - Jul 26, 2017
New St Vincent’s facility brings clinical genomics to patients on its Darlinghurst campus - Oct 26, 2016
Brown fat keeps blood sugar in check - Mar 11, 2016
Professor Don Chisholm awarded Doctor of Science by UNSW Australia - Dec 14, 2015
Exploring the paradox of metabolically healthy obesity - Nov 10, 2015
Garvan researcher wins Diabetes Society's Young Investigator Award - Sep 17, 2015
Professor Lesley Campbell wins Sir Kempson Maddox Award - Nov 24, 2014
Gastric by-pass surgery ‘curative’ in very unusual cases of diabetes - Aug 27, 2014
The ICEMAN study - how keeping cool could spur metabolic benefits - Jun 23, 2014
Evidence that shivering and exercise may convert white fat to brown - Feb 05, 2014
Garvan receives $15.5 million in NHMRC funding round - Oct 25, 2013
A complex story behind genes, environment, diabetes and obesity - Aug 08, 2013
A smart way of using testosterone to prevent muscle wasting - Jul 31, 2013
Cellular garbage may explain effects of insulin resistance and diabetes - Jan 31, 2013
Measuring distress in people with Types 1 and 2 diabetes - Jan 21, 2013
The genes that drive soft drink consumption and weight gain - Jan 18, 2013
A new way of looking at Prader-Willi Syndrome - Nov 15, 2012
Understanding why some obese people stay sensitive to insulin - Feb 01, 2012
Growing ‘brown fat’ might help us fight obesity - Sep 03, 2011
Pilot study curbs appetite of people with Prader-Willi Syndrome - Jun 27, 2011
New generation asthma drug could improve metabolism - Jun 05, 2011
James Cantley Awarded Don Chisholm Fellowship in Fundamental Diabetes Research - Oct 09, 2010
Garvan Diabetes Researcher Receives Prestigious Fellowship - Oct 06, 2010
Simple diagnostic tool predicts Type 2 diabetes in South East Asians - Jul 07, 2010
Better understanding of the all-consuming Prader-Willi Syndrome - May 12, 2010
Weight gain when there’s a family history of Type 2 diabetes - May 11, 2010
Surprising findings about Hepatitis C and insulin resistance - Mar 09, 2010
Research Fellowship announcement to support link between weight loss and the reversal of Type 2 diabetes - Oct 29, 2009
Low levels of PYY hormone a very early indicator of Type 2 diabetes - Mar 11, 2008
New Fellowship Strengthens Garvan Potential to find a cure for Type 2 diabetes - Dec 07, 2007

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