New research delves deeper into the similarities between type 1 and 2 diabetes

Matthew Waters (r) pictured with former PhD student, Dr Tenzin Dagpo (l), at work in the lab Matthew Waters, diabetes, type 1, type 2

It hasn’t always been easy to juggle, but PhD scholar Matthew Waters has no regrets about his decision to undertake a combined PhD and medical degree at the Australian National University (ANU).

“I knew I wanted to study medicine but after my honours year, I realised how much I enjoyed research. It crossed my mind that I might want to pursue research as a career,” Mr Waters said.

“At the time, ANU was the only university that offered a combined PhD/Medical degree so it was an easy choice.”

With the support of his PhD supervisor, Professor Chris Nolan, Mr Waters is in the final stages of both degrees, now writing up the results to the lab work he undertook in the first two years of his PhD.

His research to understand the overlapping characteristics between type 1 and type 2 diabetes using a unique mouse model, recently won him the Basic Science Poster Award at the 2021 Australian Diabetes Society conference.

Diabetes can affect many organs in the body, but it all starts with the pancreas. The pancreas controls sugar levels and releases insulin into the blood stream. Within the pancreas there are islets (a group of cells), and within the islets there are beta cells. It is the beta cells that are responsible for secreting insulin. If these beta-cells are damaged, it will affect their insulin production.

Type 1 diabetes is considered an autoimmune disease and accounts for only 5-10% of diabetes cases. It commonly presents in childhood. The body recognises its insulin secreting cells as foreign resulting in the autoimmune destruction of the insulin secreting cells of the pancreas. People with type 1 diabetes need insulin injections to put back into the body the insulin that it can no longer produce on its own.

Type 2 diabetes is far more common accounting for 90% of cases. It often presents when people still have some level of insulin secretion and progresses over a long period of time, often showing up later in life. People who develop type 2 diabetes typically have a defect in their insulin secretion with underlying insulin resistance. However, if it’s caught in the early stages of the disease and is managed appropriately through diet, exercise and anti-diabetic drugs, then the progression to full blown insulin-requiring diabetes, can be prevented.

“There is evidence to suggest that type 1 and type 2 diabetes are more similar than traditionally thought. For example, as the incidence of obesity has grown in recent years we’ve seen an increase in type 1 diabetes. Studies looking at genetics show that people diagnosed with type 1 diabetes are nowadays less likely to be carrying high risk genes for type 1 diabetes suggesting there are other factors at play. In addition, people are being diagnosed with type 1 diabetes later in life and type 2 diabetes earlier in life. Looking at all of this evidence together indicates things like obesity and insulin resistance may be acting as triggers for the autoimmunity seen at the beginning of type 1 diabetes,” explained Mr Waters.

Mr Waters goes on to say, “What I found in my lab work is that mice derived from a model that are prone to type 1 diabetes, fed a high-fat diet will develop a type 2 diabetes response. We believe this could be due to a defect in their insulin secreting beta cells. We think early on in the disease process the beta cells over secrete insulin, which later develops into insulin resistance and high blood glucose. The defect may lie in the beta cell hyper response to poor diet and sedentary lifestyle. In its attempt to control blood glucose it secretes more insulin causing the beta cells to become overworked, leading to exhaustion and then cell death. We think this finding could represent another pathway in the development of type 1 diabetes that is not related to the immune system. This could be a new target to protect against the development of both type 1 and type 2 diabetes but more research needs to be done in this area.”

“The other part of my research looked at the role that amino acids (or the building blocks of protein) play in the development of type 1 diabetes. Using male mice prone to type 1 diabetes and also genetically modified to excrete high levels of amino acids from their system, we investigated what would happen if they were on a high fat and sugar diet. We found that reducing amino acids led to improved glucose control, reduced insulin secretion and a better body weight profile in males, even though they had high fat and sugar diets,” Mr Waters advised.

More research will take place in future to build on these findings to further understand the commonalities between type 1 and 2 diabetes, and the prevention of type 2 diabetes.

For the immediate future, Mr Waters will be focussed on completing his clinical placements for his medical degree and spending his weekends writing up his thesis.

“There’s no doubt that research will be part of my future. Being up-to-date in the newest findings is so important for clinical work. In fact, on a ward round for my endocrine clinical placement there was discussion about new research related to the management of diabetes and elevated glucose levels in patients with COVID19. It just shows that as a medical professional you need to be across the research.”