Obesity and certain non-autoimmune genes may contribute to type 1 diabetes
A recent collaborative article led by Dr. Maria Redondo, a pediatric endocrinologist at Texas Children’s Hospital, provides current perspectives on the etiology of type 1 diabetes. This article presents evidence supporting the emerging theory that obesity and certain type 2-linked genes, may also contribute to the progression of type 1 diabetes. The article was published in the journal Diabetes Care.
Type 1 diabetes is an autoimmune disorder that affects about 1.25 million Americans and is the most common form of diabetes among children and adolescents, although it does occur in adults as well. In this condition, a patient’s body erroneously attacks and destroys specialized pancreatic cells, called the beta cells, which secrete insulin, a hormone that signals the cells to absorb glucose from the blood. Since insulin is absent or very low in these patients, their blood glucose levels remain elevated and quickly cause life-threatening situations such as organ failure. Also, higher than normal glucose can damage various organs over time.
On the other hand, type 2 diabetes is a result of progressive reduction in the amount of insulin secreted by pancreatic beta cells or due to increasing resistance of the body’s cells to insulin. Although type 2 diabetes is the most common form of diabetes in adults, it is increasingly diagnosed in children as well. Obesity, genetic predisposition, and environmental factors – such as a carbohydrate-rich diet and lack of exercise – are common causes of type 2 diabetes. Until recently, these two forms of diabetes were considered distinct conditions.
This article provides crucial insights into how factors that were previously thought to be only crucial in type 2 diabetes may also contribute to the development and progression of type 1 diabetes.
Genetics account for 50% of the risk for type 1 diabetes, with one specific genetic (HLA) region being the major contributor. Recently, genetic variants in type 2-associated regions were found in certain subsets of individuals with autoimmune type 1 diabetes. For instance, there is growing evidence to suggest that genetic variations in a specific type 2-linked genetic region (transcription factor 7-like 2) may contribute to the development of type 1 diabetes in certain individuals. This is even more likely for those who have milder form of type 1 diabetes and may therefore experience a less aggressive attack on their beta cells. In these individuals, the metabolic characteristics may present as type 2 diabetes, rather than type 1 diabetes, especially at disease onset.
In addition, increasing prevalence of obesity among children and adults is thought to be one of the contributing factors to the rising incidence of type 1 diabetes. It was proposed that excess body weight may accelerate the development and clinical onset of type 1 diabetes by increasing insulin resistance in these susceptible individuals whose ability to produce and secrete insulin is already compromised due to autoimmunity-related loss of beta cell function. Moreover, emerging data suggests that obesity can also interact with the immune (defense) system to accelerate the destruction of insulin-producing beta-cells.
This articles sheds light on an important conceptual advancement in the field of diabetes and is expected to have important far-reaching implications in various aspects of clinical management of type 1 diabetes. The authors think accounting for these additional factors that impinge on type 1 diabetes could improve various aspects of its clinical management.
For instance, adding these factors would increase the accuracy of algorithms used to predict the likelihood of which patients will develop type 1 diabetes. Also, based on this work, preventive strategies for type 1 diabetes, which are currently focused on immunomodulatory treatments, could be expanded in the future to also include approaches that address obesity and modulation of genes that affect glucose metabolism.
Finally, this conceptual advancement seeks to shift treatment paradigms for type 1 diabetic individuals by broadening the scope to include additional contributing factors.