Type 1 Diabetes Mellitus is a syndrome characterized by hyperglycemia and insulin deficiency resulting from the loss of beta cells in pancreatic islets (Mapes & Faulds, 2014). Nonimmune (type 1B diabetes), occurs secondary to other diseases and is much less common than autoimmune (type 1A). The destruction of beta cells in Type 1A diabetes results from the interaction of both genetic and environmental factors. Although the genetic susceptibility is not well understood, type 1 diabetes is most strongly associated with major histocompatibility complex (MHC), specifically histocompatibility leukocyte antigen (HLA) class II alleles (HLA-DQ and HLA-DR) (McCance & Heuther, 2014). Type 1 diabetes is less hereditary than type 2 but 7-13% of patients also have a first degree relative with type 1 diabetes (Mapes & Faulds, 2014). Environmental factors include viral infections (especially enteroviruses), exposure to infectious microorganisms (such as Helicobacter pylori), exposure to cow’s milk proteins and a lack of vitamin D (McCance & Heuther, 2014).
The destruction of insulin-producing beta cells in the pancreas starts with the formation of autoantigens. These autoantigens are ingested by antigen-presenting cells which activate T helper 1 (Th1) and T helper 2 (Th2) lmphocytes. Activated Th1 lymphocytes secrete interluekin-2 (IL-2) and interferon. IL-2 activates autoantigen-specific T cytotoxic lymphocytes which destroy islet cells through the secretion of toxic perforins and granzymes. Interferon activates macrophages and stimulates the release of inflammatory cytokines (including IL-1 and tumor necrosis factor [TNF]) which further destroy beta cells (McCance & Heuther, 2014). Activated Th2 lymphocytes produce IL-4 which stimulates B lymphocytes to proliferate and produce islet cell autoantibodies (ICAs) and anti-glutamic acid decarboxylase (antiGAD65) antibodies. AntiGAD65 is an enzyme that helps control the release of insulin from beta cells and can be used to determine the cause of diabetes (McCance & Heuther, 2014). Insulin autoantibodies [IAAs]) and zinc transporter 8 (Znt8) protein are also associated with type 1 diabetes mellitus. Despite it’s complicated pathophysiology, it is important to understand the destruction of beta cells in type 1 diabetes because it leads to a lack of insulin and amylin. Without insulin or amylin the body cannot promote glucose disappearance or limit glucose appearance from the bloodstream, respectively, resulting in hyperglycemia (Mapes & Faulds, 2014).
Type 1 diabetes does not present clinically until 80-90% of the beta cells have been destroyed (McCance & Heuther, 2014). Because insulin stimulates glucose uptake into tissues, stores glycose as glycogen, inhibits glucagon secretion and inhibits glucose production from the liver, the destruction of insulin-producing beta cells causes hyperglycemia (Mapes & Faulds, 2014). Type 1 diabetics may present with abrupt onset of diabetic ketoacidosis, polyuria, polyphagia, polydipsia, or rapid weight loss with marked hyperglycemia (Mapes & Faulds, 2014). To diagnose diabetes, patients must have an A1C level greater than 6.5% percent on two separate tests; the presence of ketones in the urine and/or autoantibodies in the blood can distinguish type 1 from type 2 diabetes (Mayo Clinic, 2014).