DRWF Research Manager Dr Eleanor Kennedy reports from the American Diabetes Association 79th Scientific Sessions in San Francisco, USA.
The penultimate day of the ADA conference starts with the Outstanding Scientific Achievement Award Lecture given, this year by Professor Sadaf Farooqi from the University of Cambridge.
Entitled Obesity and the Biology of Weight Regulation, Professor Farooqi’s research focusses on severe obesity and people with this have the highest burden of complications.
Deaths from diabetes increase by more than 116% per 5 body mass index (BMI) units and there is, of course, an additional impact upon education, employment and wide-spread stigma. Professor Farooqi points out that obesity is not a new issue, however.
In the 5th century BC, the ancient Greek physician, Hippocrates, said that “Corpulency is not only a disease, but a harbinger of others,” recognising what we now understand as sleep apnea and infertility as complications of obesity but, as she explains, some people are predisposed to severe obesity and the genetics and hormones behind these forms of obesity are being unravelled by her group and others around the world.
One molecule of extreme interest is the melanocortin 4 receptor (MC4R). Coding alterations in this represent the commonest genetic form of obesity with around 300 recognised mutations and mutations in this gene can account for up to 1% of severely obese adults and 3-5% of severely obese children.
Setmelanotide is a drug that targets MC4R and, in early phase clinical trials, it has been shown to lead to weight loss in a subset of people with MC4R deficiency.
This molecule is now in phase 2/3 trials in multiple genetic obesity syndromes and, who knows, maybe one day can lead to a treatment for obesity.
In addition to looking at extreme forms of human obesity, Professor Farooqi is interested in the genetics of those who remain thin regardless of what they eat.
Professor Farooqi explained that thin people are thin because they have less of the genetic variants that make people obese adding that it was not because they are morally superior which causes a packed auditorium to erupt with laughter.
Following her highly enjoyable and informative seminar, I walk across the street in the unseasonably hot San Francisco weather to sit in on a new session introduced by the Scientific Sessions Meeting Planning Committee for this year. This very innovative session was entitled, Major Advances and Discoveries in Diabetes - The Year in Review.
The clinical highlights of the past 12 months have been identified by Professor Dan Drucker from the Lunenfeld-Tanenbaum Research Institute in Toronto whilst Professor Juleen Zierath from the Karolinska Institute in Stockholm, Sweden tackles the basic science side.
It was a fascinating retrospective journey through the highlights of the last year.
Professor Drucker’s choices of clinical achievement includes work that was reported just a few days ago here at the ADA conference. Researchers investigating the type 1 world recruited relatives of patients with type 1 diabetes who did not have diabetes but who were at high risk for the development of the clinical disease.
Patients were randomly assigned to a single 14-day course of teplizumab, a monoclonal antibody therapy, or placebo, and followed up for progression to type 1 diabetes every six months for a period of five years.
This was a small study with just 44 people randomly assigned to receive the drug. Of these, 19 (43%) developed diabetes. By comparison, among the 32 people who received a placebo, 23, (72%) developed diabetes.
When the study was stopped, the percentage of participants who remained free of diabetes was twice as high in the teplizumab group (57%) compared with the placebo group (28%).
This one is being hailed as a really major advance in the field so let’s watch this space.
But, when Professor Juleen Zierath stepped up to the podium, she announced that she had whittled down an entire year’s worth of thousands of basic scientific publications to just 18 that had made a significant and very real impact.
One of these was written by the former chairman of the Research Advisory Committee for the DRWF’s sister organisation in Sweden, Professor Leif Groop. And the second was authored by the current chairman of the same committee, Professor Fredrik Backhed.
Professor Groop’s work was into the detection of novel sub-groups of adult-onset diabetes and their association with outcomes. His team identified five clusters of patients with diabetes based on a number of different parameters including age at diagnosis, body mass index and blood glucose control.
The impact of this is that interventions or treatments could be tailored to individuals based on individual risks and this takes us back to some of my previous blogs from the ADA conference about personalised or precision medicine which continues to be a very hot topic.
Professor Backhed’s work focusses on another hot topic in diabetes research at the moment – the gut microbiome.
Gut microbiota has been associated with several disease conditions. His group discovered a pathway revolving around a molecule called imidazole proprionate which is known to be increased in people with type 2 diabetes.
It appears to contribute directly to the development of insulin resistance, a hallmark of type 2 diabetes. Clearly, the next step is for clarification on the interplay between diets, bacteria and the gut environment to ascertain the role of imidazole proprionate.
But the research that got the biggest gasps? Well, that would be research on cavefish!
These animals live, as the name would suggest, in caves, deep underwater and they never venture to the surface so they have no pigmentation.
They also have significantly higher fasting blood glucose levels and features of insulin resistance. It turns out that this is caused by a mutation in the insulin receptor which leads to hyperglycaemia.
Yet cavefish are completely healthy and have a normal lifespan as far as cavefish are concerned so we need a deeper analysis of these strange fish to uncover the underlying evolutionary forces responsible for these striking metabolic adaptations as they may shine light on the issues of hyperglycaemia and insulin resistance in us surface dwellers!
As I walk home that evening, I can only marvel at the lengths that researchers will go to try and work out what causes diabetes.
Cavefish? I mean, who knew?!
And I feel equally delighted that the people DRWF and her sister organisations across Europe have working with them are not only responsible for helping us to fund the best research that we can. They’re actually doing some of the best research.
I’d say that this deserves a glass of wine!