Understanding the complexity of this multifactorial disease has been the holy grail of diabetes research for many decades. The relative importance of insulin resistance and pancreatic beta cell dysfunction in the pathogenesis of T2D has long been debated. However, T2D only ensues in individuals who develop progressive pancreatic beta cell failure, thereby releasing insufficient amounts of insulin to compensate for insulin resistance. This leads to metabolic dysfunction characterised by hyperglycaemia, increased circulating free fatty acids and amino acids. Understanding the causes, aetiology and progression of T2D therefore requires an integrative multidisciplinary approach that combines experimental and clinical work with state-of-the-art computational analysis and modelling.
T2D has a well-recognised genetic contribution. Many of the genes identified are associated with pancreatic beta cell gene regulation and function. Environmental factors, such as increased caloric intake (particularly saturated fats), and decreased energy expenditure, also play an essential role in the pathogenesis of the disease.
It is possible that T2D represents a heterogeneous group of diseases. The current 'state-of-the-art' of T2D diagnosis is the finding of elevated plasma glucose or glycated haemoglobin (HbA1c) levels most often in obese, sedentary and/or elderly people.
One of the major obstacles to understanding pancreatic beta cell dysfunction is that the human islets of Langerhans are inaccessible. They are tiny cell clusters scattered throughout the pancreas. Over recent years it has become clear that animal pancreatic islets of Langerhans do not represent the same complexity as those found in humans. Where human islets of Langerhans have become available for research several European laboratories have been able to begin collecting large amounts of genetic data and information to help understand pancreatic beta cell dysfunction at the molecular level in humans.
Being able to accumulate, analyse and interpret the genetic information could allow a breakthrough in understanding the molecular basis of the disease and the potential to identify new therapies or prevention strategies for patients.