Type 1 diabetes is an autoimmune condition caused by destruction of pancreatic beta cells by an individual’s own T cells. Beta cells produce the hormone insulin, which is required for glucose metabolism and energy production. Thus beta cell loss has devastating effects on multiple organ systems. The etiology of type 1 diabetes differs significantly from that of, more common, type 2 diabetes, in which cells become insulin-insensitive in part due to lifestyle choices.

Each year approximately 30,000 people in the US—more than of them half children—are newly diagnosed with type 1 diabetes (also called “juvenile diabetes”), and currently about 2 million Americans live with the disease. There is no cure: patients closely monitor blood glucose levels and take corrective insulin daily, orally or by injection. Despite this onerous regimen, many develop complications such as kidney damage, neuropathy or blindness.

LJI investigator Matthias von Herrath, M.D., leads the fight against diabetes from two fronts: he heads LJI’s Diabetes Research Center and, at the same time, directs a translational diabetes center in Seattle run by the Danish healthcare company Novo Nordisk.

When in Seattle, von Herrath focuses on developing immunotherapy for diabetes, while at LJI he conducts basic research into its molecular and cellular underpinnings. Many of his studies are conducted in partnership with the Network for Pancreatic Organ donors with Diabetes (nPOD), which provides pancreatic tissues from diabetic organ donors to researchers at leading diabetes centers.

The Ups and Downs of Type 1 Diabetes
From this collaboration, has emerged one of von Herrath’s key discoveries, namely that the disease doesn’t progress steadily but instead occurs in a nonlinear pattern physicians call relapsing/remitting. In that “pre-diabetic” and possibly asymptomatic period, T cell populations likely shift back and forth between cytotoxic and more benign players before beta cells undergo total destruction (and patients seek treatment).

This means that there is a window of time, potentially detectable, during which loss of irreplaceable pancreatic cells that could be prevented by drugs that modulate the immune response. Von Herrath’s work also hints that viral infection may accelerate disease progression, and high on his current list of suspects is human herpesvirus 6 (HVP6). Interestingly, HVP6 has also been linked to autoimmune destruction of the thyroid gland (in Hashimoto’s Disease) and to multiple sclerosis.

Pursuing the infection angle, a team led by Nunzio Bottini, M.D., Ph.D., discovered that mutations in a gene encoding, a signaling protein, called a phosphatase significantly increases the risk of type 1 diabetes, possibly by allowing infection by an enterovirus already known to trigger the disease. These studies could encourage creation of personalized vaccines to counter specific infections in individuals at risk of the disease.