It’s a difficult topic, but one we can’t ignore. Half of the world is overweight and this is causing serious health problems. Here in Australia, that percentage is even higher – 65%.
And almost 30% of us are obese (a body mass index over 30 kg/m2). And it’s about more than just extra weight.
Obesity increases the risk of many other diseases – and this year, obesity was recognised as a disease itself.
“Our strength here at Garvan is understanding the metabolic consequences of being overweight in an individual,” says Dr Dorit Samocha‑Bonet, clinical scientist and dietitian with the Diabetes and Metabolism Division. “Obesity is very easily diagnosed, you do not need sophisticated equipment. But, the metabolic impairments are diverse. Each person is different.”
One of the major conditions travelling hand-in-hand with obesity is prediabetes – the precursor to type 2 diabetes in which blood sugar is abnormally high, mostly after meals. “Prediabetes affects around 40% of American adults and here in Australia we are following the same trend,” says Dorit.
Prediabetes can fly under the radar for years – until the symptoms crash down like Jenga blocks. Prediabetes on its own is a risk factor for everything that diabetes can herald – cardiovascular disease, certain types of cancer, fatty liver. “It’s not just a marker of a disease to come, a person with prediabetes could already have many of those conditions that are affected by type 2 diabetes.”
But if we do know about prediabetes (and being overweight is one of the warning signs) there’s a lot we can do, explains Dorit. This is the focus of Garvan’s new clinical trial PREDICT. “When you are already diagnosed with diabetes, it can be too late for your pancreas, because your body has been dealing with insulin resistance for many years. But during prediabetes it’s possible to prevent the development of type 2 diabetes.”
Here’s the twist
It seems like the solution is straightforward – lose weight and prevent diabetes. But, as we all know, many people struggle to lose weight and sustain the reduction. “I acknowledge how hard it is for people to lose weight. The percentage of people who maintain weight loss after five years is less than 20%,” says Dorit, who has practised as a dietitian for more than 20 years.
Also, weight loss does not reverse prediabetes in everybody. “On average, weight loss of about 5% of body weight, if maintained, is very beneficial for health. But we see in the clinic, and it has been documented in medical literature, that many individuals who lose a large amount of body weight and fat, do not reverse prediabetes.
“Glucose regulation remains impaired in these individuals. It’s clear that weight loss as a blanket treatment for everybody isn’t the whole story in battling the prediabetes epidemic.”
Which leads us to the gut
Across the board, scientists, more than ever before, are investigating the role of the microorganisms living in our gut (our microbiome) in the current diabetes epidemic. “Our collaborators at the Weizmann Institute in Israel have shown that some foods can cause blood sugar to spike in some people, but have no effect on others – and that the sugar response to food can be predicted by the composition of the gut microorganisms and other clinical and blood parameters.”
Diabetes researchers also saw another signpost pointing towards the microbiome as a key contributor to response to diabetes therapy – a 60 ‑year‑old medication called metformin. It is a commonly prescribed drug for type 2 diabetes.
“We know that this drug makes people more sensitive to insulin – it fights insulin resistance – but we’re still figuring out the exact mechanism. From large clinical studies, we know that 20 to 40% of individuals with prediabetes or type 2 diabetes have a poor response to metformin. But it’s emerging that metformin affects the gut microorganisms in a positive way,” says Dorit.
Know your microbiome
This led Dorit to want to find out more about the relationship between gut microorganisms and the way we respond to metformin. She has surmised, and will study in the PREDICT clinical trial, that the genetic makeup of the billions of microorganisms in your gut could be the differentiator in how well your body processes sugar after meals and how you respond to common treatments like weight loss and metformin.
“At the moment, our standard of care for a person with prediabetes is to advise a low fat, low sugar diet and try to be more active, to lose weight. But we’re looking for more precise ways to treat people.”
Going forward, Garvan’s aim is to translate findings from the PREDICT study to provide tools for clinicians to guide patients on medication, diet and lifestyle choices. This will hopefully help clinicians and their patients stop prediabetes from progressing to full-blown type 2 diabetes and to assist those living with diabetes to gain more tools to manage their health and achieve better quality of life.
The PREDICT Clinical Trial
During the six-month study, participants will wear a continuous glucose monitor for two weeks before and during treatment.
Participants will document all food intake in a specialised mobile phone app.
The PREDICT clinical trial is currently taking enrolments of men and women aged 20 -70 years who have prediabetes (e.g. you have been told you are at risk of developing type 2 diabetes or you have had increased blood sugar in previous blood tests) or recently diagnosed type 2 diabetes, not yet treated with a sugar- lowering medication. Study visits are conducted at the Garvan Institute of Medical Research and St Vincent’s Hospital, Darlinghurst, Sydney.
Principal Investigators: Professor Jerry Greenfield and Dr Dorit Samocha-Bonet
Phone: (02) 9295 8215
ClinicalTrials.gov ID: NCT03558867 St Vincent’s HREC Ref: 17/SVH/080