April 14, 2016 - Pathogenesis of DM1

Question 1

Genetic Susceptibility of Diabetes Type 1

Answer 1

It is a mix of genetic and environmental factors.

Without a family history, there is less than a 1% chance of developing diabetes.

With identical twins, there is only a 40% chance.

Question 2

IPEX Syndrome

Answer 2

Immunodysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a rare disease linked to the dysfunction of FOXP3, which is widely considered to be the master regulator of the regulatory T-cell lineage.

This leads to the dysfunction of regulatory T-cells and the subsequent autoimmunity.

Only affects males. Can present with many autoimmune diseases and causes severe enlargement of secondary lymphoid organs, diabetes, eczema, food allergies, and infections.

Question 3

APECED (or APS-1)

Answer 3

Autoimmune Polyendocrinopathy Candidiasis-Ectodermal Dystrophy (APECED) is a subtype of autoimmune polyendocrine syndrome in which multiple endocrine glands dynsfunction as a result of autoimmunity.

It is a genetic disorder which is inherited in an autosomal recessive fashion due to a defect in the AIRE (auto immune regulator) gene which is located on chromosome 21 and normally confers immune tolerance.

Often presents as a mild immune deficiency, leading to persistent mucosal and cutaneous infections with candida yeasts. Also, decreased function of the spleen resulting in small size.

Question 4

Non-Monogenic Forms of DM1

Answer 4

70 putative loci, but 2 are definitely confirmed

These account for 50-60% of heritability

Question 5

Molecular Mimicry

Answer 5

That the antigens on our own cells might be similar to those that had an antibody trying to target them, and they get accidentally caught in the crossfire and antibodies are produced against your own cells.

Question 6

Viruses and Diabetes

Answer 6

Viruses may play a role by direct destruction of beta cells, acting as a superantigen, partially damaging beta cells which exposes new antigens to the body, and by acting as a molecular mimic.

Question 7

MODY

Answer 7

Mature-Onset Diabetes in the Young

Refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene, which disrupts insulin production.

Because it is autosomal dominant, usually patients present with a strong family history of diabetes, and they present with diabetes-like symptoms in the 2nd to 5th decade of life.

May make up to 5% of all diabetes cases. Making the right diagnosis is important because it changes the management of the diabetes. Different types of MODY respond to different types of treatment, and insulin may not be required.

Question 8

Mitochondrial Disease

Answer 8

A group of disorders caused by dysfunctional mitochondria.

Maternal transmission only

Symptoms often include poor growth, loss of muscle coordination, muscle weakness, visual problems, learning disabilities, heart disease, liver disease, kidney disease, GI disorders, respiratory disorders, neurological problems etc.

Examples can include diabetes mellitus and deafness (DAD), and mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptoms (MELAS), among many others.