Seasonal ‘link’ to Type 1 diabetes
JDRF researchers at the University of Cambridge have found evidence that our immune systems change with the seasons – a finding that may suggest a seasonal link to Type 1 diabetes.
Scientists have known for some time that diagnosis rates of various conditions, including cardiovascular disease and Type 1 diabetes, vary with the seasons. However, this is the first time that researchers have shown that this may be down to seasonal changes in how our immune systems function.
The study, published in the journal Nature Communications, showed that the activity of almost a quarter of our genes (5,136 out of 22,822 genes tested) differs according to the time of year, with some more active in winter and others more active in summer. This seasonality also affects our immune cells and the composition of our blood and adipose tissue (fat), the study says.
The implications for how we treat disease like Type 1 diabetes, and even how we plan our research studies, could be profound
Professor John Todd, Director of the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, said: “This is a really surprising – and serendipitous – discovery as it relates to how we identify and characterise the effects of the susceptibility genes for Type 1 diabetes. In some ways, it’s obvious – it helps explain why so many diseases, from heart disease to mental illness, are much worse in the winter months – but no one had appreciated the extent to which this actually occurred. The implications for how we treat disease like Type 1 diabetes, and even how we plan our research studies, could be profound.”
An international team, led by researchers from the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory in the Department of Medical Genetics, Cambridge Institute for Medical Research, examined samples from over 16,000 people living in both the northern and southern hemispheres, in countries including the UK, USA, Iceland, Australia and The Gambia. These samples included a mixture of blood samples and adipose tissue.
The researchers used a variety of techniques to study the samples, including looking at the cell types found in the blood and measuring the level of expression of the individuals’ genes – a gene is said to be ‘expressed’ when it is active in a particular cell or tissue, usually involving the generation of proteins. They found that the thousands of genes were expressed differently in blood and adipose tissue depending on what time of year the samples were taken. Similarly, they identified seasonal differences in the types of cells found in the blood.
Seasonal differences were present across mixed populations in geographically and ethnically diverse locations – but the seasonal genes displayed opposing patterns in the northern and southern hemispheres. However, the pattern of seasonal activity was not reflected as strongly in Icelandic donors. The researchers speculate that this may be due to the near-24 hour daylight during summer and near-24 hour darkness in winter.
One gene of particular interest was ARNTL, which was more active in the summer and less active in the winter. Previous studies have shown that, in mice at least, the gene suppresses inflammation, the body’s response to infection; if the gene has the same function in humans, then levels of inflammation will be higher during winter in the northern hemisphere. Inflammation is a risk factor for a range of diseases and hence in winter, those at greatest risk will likely reach the ‘threshold’ at which the disease becomes a problem much sooner. Drugs that target the mechanisms behind inflammation could offer a way of helping treat these diseases more effectively during the winter periods.
A particularly surprising finding was that a set of genes associated to an individual’s response to vaccination was more active in winter, suggesting that some vaccination programmes might be more effective if carried out during winter months when the immune system is already ‘primed’ to respond.
During European and Australian winters, they argue, the thresholds required to trigger an immune response may be lower as a direct consequence of our coevolution with infectious organisms, which tend to be more prevalent during winter. Interestingly, people from The Gambia showed distinct seasonal variation in the numbers of immune cells in the blood that correlated with the rainy season (June-October), during which time infectious diseases, particularly mosquito-borne diseases such as malaria, are more rife.
Karen Addington, Chief Executive of JDRF in the UK, said: “We have long known there are more diagnoses of Type 1 diabetes in winter. This study begins to reveal why. It identifies a biological mechanism we didn’t previously know of, which leaves the body seasonally more prone to the autoimmune attack seen in type 1 diabetes.
“While we all love winter sun, flying south for the whole of each winter isn’t something anyone can practically recommend as a way of preventing type 1 diabetes. But this new insight does open new avenues of research that could help untangle the complex web of genetic and environmental factors behind a diagnosis.”