Clinical Diabetes, Appetite and Metabolism Lab

Exploring new medications for the treatment of type 1 diabetes

Type 1 diabetes is associated with an increased risk of heart disease. Even with our best treatments, this risk remains present even after treating diabetes, along with the risk of high cholesterol and high blood pressure. However, many drugs used to treat the more common disease of type 2 diabetes can lower the risk of heart disease. Our lab is investigating whether existing treatments for type 2 diabetes can reduce the risk of cardiovascular disease in patients with type 1 diabetes. The therapies we are trialling include metformin and a class of drugs called GLP-1 receptor agonists, which can lead to weight loss in people with and without diabetes.

Identifying the genetic causes of metabolic diseases and disorders

Our lab is also focused on the challenge of modern times: that evolution has left many of us with good survival genes which make us prone to gaining weight easily and developing type 2 diabetes.

We have discovered that healthy relatives of people with type 2 diabetes may carry genes for obesity (explaining why so many gain weight easily). Our studies have detected possible pathophysiological precursors in otherwise healthy at-risk subjects. For instance, one study showed that healthy relatives of people with type 2 diabetes gained more weight than those who didn’t have diabetic relatives, when asked to overeat for one month.

In addition to this, we have identified a group of overweight and obese individuals who appear to be at lower risk of diabetes and heart disease than other individuals with obesity. A major focus of our lab is to establish the factors that confer this metabolic protection and to devise a set of 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 seek to identify what protects this cohort and whether they remain at lower risk of metabolic disease over long periods of time.

Another focus of our lab 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), genetic syndromes of obesity (such as Prader-Willi syndrome), lipodystrophies (partial and generalised) and monogenic diabetes (previously known as MODY – Maturity Onset Diabetes of the Young).

Our mission is to continue the clinical phenotyping of disease or pre-disease states, by searching for biomarkers or genetic insights into causation. Identifying people predisposed to developing diabetes will allow pre-emptive treatment and the reversal of contributing metabolic conditions. By providing this preventative healthcare, patients will be able to better manage their symptoms before they escalate in severity, while potentially reducing the risk of developing serious secondary complications, like heart disease, kidney disease and neuropathy.