Autoimmune disorders
People with type 1 diabetes are at an increased risk for developing several autoimmune disorders, particularly thyroid problems – around 20% of people with type 1 diabetes have hypothyroidism or hyperthyroidism, typically caused by Hashimoto thyroiditis or Graves disease respectiveley. Celiac disease affects 2–8% of people with type 1 diabetes, and is more common in those who were younger at diabetes diagnosis, and in white people. Type 1 diabetics are also at increased risk of rheumatoid arthritis, lupus, autoimmune gastritis, pernicious anemia, vitiligo, and Addisons disease. Conversely, complex autoimmune syndromes caused by mutations in the immunity-related genes AIRE (causing autoimmune polyglandular syndrome), FoxP3 (causing IPEX syndrome), or STAT3 include type 1 diabetes in their effects. Epidemiology
Type 1 diabetes makes up an estimated 10–15% of all diabetes cases  or 11–22 million cases worldwide. Symptoms can begin at any age, but onset is most common in children, with diagnoses slightly more common in 5 to 7 year olds, and much more common around the age of puberty. In contrast to most autoimmune diseases, type 1 diabetes is slightly more common in males than in females.In 2006, type 1 diabetes affected 440,000 children under 14 years of age and was the primary cause of diabetes in those less than 15 years of age.Rates vary widely by country and region.
This accounts for the lack of glucagon stimulation and epinephrine release that would normally stimulate and enhance glucose release and production from the liver, rescuing the diabetic from severe hypoglycemia, coma, and death. Numerous hypotheses have been produced in the search for a cellular mechanism of hypoglycemic unawareness, and a consensus has yet to be reached. The major hypotheses are summarized in the following table:
In addition, autoimmune diabetes is characterized by a loss of islet specific sympathetic innervation. This loss constitutes an 80–90% reduction of islet sympathetic nerve endings, happens early in the progression of the disease, and is persistent though the life of the patient. It is linked to the autoimmune aspect of type 1 diabetics and fails to occur in type 2 diabetics. Early in the autoimmune event, the axon pruning is activated in islet sympathetic nerves. Increased BDNF and ROS that result from insulitis and beta cell death stimulate the p75 neurotrophin receptor (p75NTR), which acts to prune off axons. Axons are normally protected from pruning by activation of tropomyosin receptor kinase A (Trk A) receptors by NGF, which in islets is primarily produced by beta cells. Progressive autoimmune beta cell destruction, therefore, causes both the activation of pruning factors and the loss of protective factors to the islet sympathetic nerves. This unique form of neuropathy is a hallmark of type 1 diabetes, and plays a part in the loss of glucagon rescue of severe hypoglycemia.