Health

Diabetes mellitus type 1 (Type 1 diabetes, T1DM, IDDM, or, formerly, juvenile diabetes) is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas.[2] The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.[3]

Incidence varies from 8-17/100,000 in Northern Europe and the U.S., with a high of about 35/100,000 in Scandinavia, to a low of 1/100,000 in Japan and China.[4]

Eventually, type 1 diabetes is fatal unless treated with insulin. Injection is the most common method of administering insulin; other methods are insulin pumps and inhaled insulin. Pancreatic transplants have been used. Pancreatic islet cell transplantation is experimental, though growing.[5]

Most people who develop type 1 are otherwise healthy.[6] Although the cause of type 1 diabetes is still not fully understood, it is believed to be of immunological origin.

Type 1 can be distinguished from type 2 diabetes via a C-peptide assay, which measures endogenous insulin production.

Type 1 treatment must be continued indefinitely in all cases. Treatment is not intended to significantly impair normal activities, and can be done adequately if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment remains quite burdensome for many people. Complications may be associated with both low blood sugar and high blood sugar, both largely due to the non-physiological manner in which insulin is replaced. Low blood sugar may lead to seizures or episodes of unconsciousness and requires emergency treatment. High blood sugar may lead to increased fatigue and can also result in long term damage to organs.

The classical symptoms of type 1 diabetes include: polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), fatigue, and weight loss.[3]

Insulin-dependent [[diabetes] characterized by dramatic and recurrent swings in glucose levels, often occurring for no apparent reason, is sometimes known as brittle diabetes, unstable diabetes or labile diabetes, although some experts say the "brittle diabetes" concept "has no biologic basis and should not be used".[7] The results of such swings can be irregular and unpredictable hyperglycemias, frequently involving ketosis, and sometimes serious hypoglycemias. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.[8]

Cause

Diabetes type I is induced by a combination of genetic susceptibility, a diabetogenic trigger and exposure to a driving antigen.[9]

Genetics

Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its onset. Depending on locus or combination of loci, it can be dominant, recessive, or somewhere in between. The strongest gene, IDDM1, is located in the MHC Class II region on chromosome 6, at staining region 6p21. Certain variants of this gene increases the risk for decreased histocompatibility characteristic of type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301, DQB1 0302 and DQB1 0201, which are common in North Americans of European ancestry and in Europeans.[10] There are also variants that appear to be protective.[10]

The risk of a child developing type 1 diabetes is approximately 10% if the father has it, approximately 10% if a sibling has it, approximately 4% if the mother has type 1 diabetes and is/was aged 25 or younger when the child is/was born, and approximately 1% if the mother is/was over 25 years old when the child is/was born.[11]

Environmental

Environmental factors can influence expression of type 1. A study showed that for identical twins, when one twin had type 1 diabetes, the other twin only had type 1 30%–50% of the time. Despite having exactly the same genome, one twin had the disease, where the other did not; this suggests that environmental factors, in addition to genetic factors, can influence disease prevalence.[12] Other indications of environmental influence include the presence of a 10-fold difference in difference among Caucasians living in different areas of Europe, and a tendency to acquire the incidence of the disease of the destination country for people who migrate.[9]

Virus

One theory, discussed by DeLisa Fairweather & Noel R. Rose, among others,[13] proposes that type 1 diabetes is a virally triggered autoimmune response in which the immune system attacks virus infected cells along with the beta cells in the pancreas. The Coxsackie virus family or Rubella is implicated, although the evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans are destroyed decreasing endogenous insulin production. This distinguishes type 1's origin from type 2 DM. The type of diabetes a patient has is determined only by the cause—fundamentally by whether the patient is insulin resistant (type 2) or insulin deficient without insulin resistance (type 1).

This vulnerability is not shared by everyone, for not everyone infected by the suspected organisms develops type 1 diabetes. This has suggested presence of a genetic vulnerability[14] and there is indeed an observed inherited tendency to develop type 1. It has been traced to particular HLA genotypes, though the connection between them and the triggering of an auto-immune reaction is still poorly understood.

Diet

There is a growing body of evidence that diet may play a role in the development of type 1 diabetes, through influencing gut flora, intestinal permeability, and immune function in the gut; wheat in particular has been shown to have a connection to the development of type 1 diabetes, although the relationship is poorly understood.[15]

Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins.[16] No connection has been established between autoantibodies, antibodies to cow's milk proteins, and type 1 diabetes. A subtype of type 1 (identifiable by the presence of antibodies against beta cells) typically develops slowly and so is often confused with type 2. In addition, a small proportion of type 2 cases manifest a genetic form of the disease called maturity onset diabetes of the young (MODY).[citation needed]

Vitamin D in doses of 2000 IU per day given during the first year of a child's life has been connected in one study in Northern Finland (where intrinsic production of Vitamin D is low due to low natural light levels) with an 80% reduction in the risk of getting type 1 diabetes later in life. The causal connection, if any, is obscure.

Short breast-feeding period and short attendance to day care is associated with the risk of type 1 diabetes in Czech children.[17]

Chemicals and drugs

Some chemicals and drugs preferentially destroy pancreatic cells. Pyrinuron (Vacor, N-3-pyridylmethyl-N'-p-nitrophenyl urea), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 diabetes after accidental or intentional ingestion. Vacor was withdrawn from the U.S. market in 1979, but is still used in some countries. Zanosar is the trade name for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer; it also kills beta cells, resulting in loss of insulin production. Other pancreatic problems, including trauma, pancreatitis or tumors (either malignant or benign), can also lead to loss of insulin production.

Pathophysiology

The pathophysiology in diabetes type I is basically a destruction of beta cells in the pancreas, regardless of which risk factors or causative entities have been present.

Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is an autoimmune response towards beta cells, involving an expansion of autoreactive CD4+ and CD8+ T helper cells, autoantibody-producing B cells and activation of the innate immune system.[10]