Immunology or Metabolism – What can we say about Type 1 Diabetes?

Diabetes

Not always easy to categorize this disorder. What is being said today? An overview of opinions around the litterature

I conducted a small litterature search with the keywords “Type 1 Diabetes”, “Immunology”, “Metabolism”, “Metabolic”. PubMed returned 534 results. Google Search returned over 5 million…

I will start with some definition as well as resources and then try to answer the question.

 

Definition

Diabetes is not a single disease.

An excellent starting point is the Diabetes Journal Article: Diagnosis and Classification of Diabetes Mellitus. It says that “Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Several pathogenic processes are involved in the development of diabetes. These range from autoimmune destruction of the β-cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action.” We have a good point here saying its origins are coming from an immune system dysfunction.

The American Diabetes Association provides in-depth overview of the symptoms, diagnosis, Type 1 and Type 2 as well as gestational. The website is full of stats and resources.

The CDC also contributes to knowledge and awareness with this comprehensive infographics. The IDF – International Diabetes Federation – is another source of information together with the WHO dedicated page on diabetes and the European Foundation for the Study of Diabètes.

CDC_diabetes-infographic

 

Some possible answers – Immunology vs. Metabolism

Coming back to Type 1 diabetes and my quick litterature search. From the 534 articles, I selected 5 among them seeming more relevant to start answering the question.

One of the first article I read is clearly stating that “Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells”. But authors of another article insist on the metabolic abnormalities in Type 1 diabetes: “Clinical onset of type 1 diabetes (T1D) is thought to result from a combination of overt beta cell loss and beta cell dysfunction. However, our understanding of how beta cell metabolic abnormalities arise during the pathogenesis of disease remains incomplete. Despite extensive research on the autoimmune nature of T1D, questions remain regarding the time frame and nature of beta cell destruction and dysfunction.” “Determining the time frame of beta cell destruction and identifying metabolic mechanisms that drive beta cell dysfunction has high potential for successful interventions to maintain insulin secretion for individuals with established T1D as well as those with prediabetes.”

A study has been done to see whether any genetic link could justify the apparition and severity of T1D in children by looking at autoimmune diseases in the extended family. The short conclusion is that approximately 30% of children with newly diagnosed T1D have a 1st and or 2nd-degree relative affected by an autoimmune disease like autoimmune thyroiditis, celiac disease, Addison’s disease, pernicious anemia, rheumatoid arthritis and multiple sclerosis. Moreover, between 9 and 19% of the children with T1D have another autoimmune disease.

An interesting point is made about the influence of the microbiome both on metabolism and immune system. For the time being only mice have been used but the results have good chances to be extrapolable to humans. “Emerging evidence suggests that both host metabolism and immune function is crucially regulated by the intestinal microbiome. Recently, we showed that in the non-obese diabetic (NOD) mouse model of Type 1 Diabetes (T1D), the gut commensal microbial community strongly impacts the pronounced sex bias in T1D risk by controlling serum testosterone and metabolic phenotypes”.

Additionally, LADA (Latent Autoimmune Diabetes of the Adult), Type 1 diabetes diagnosed during adulthood seems to have a mix of genetic characteristics from childhood-onset Type 1 diabetes and Type 2 diabetes. “Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes”, as said in the article. In this case, we probably have a mix of immunological and metabolic changes leading to the disease.

I’m not sure whether one day we will be able to really discover the autoimmune or metabolic origins of T1D. It is probably a mix of both as complex disruptions and dysfunctions in the human body are leading to T1D onset.

 

Selected articles used

Latent autoimmune diabetes of the adult: current knowledge and uncertainty – 2015

Alteration of regulatory T cells in type 1 diabetes mellitus: a comprehensive review – 2015

Metabolic abnormalities in the pathogenesis of type 1 diabetes – 2014

Microbiome manipulation modifies sex-specific risk for autoimmunity – 2014

Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes – 2013

 

Image Source

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s