Causes of Type 1 Diabetes (1A, 1B): Genetic and Environmental factors

Type 1 Diabetes Mellitus (DM) Causes

Type 1 Diabetes or also known as insulin dependent diabetes mellitus or IDDM usually has its onset before 30 years, most often in childhood or adolescence. Type 1 DM is characterized by:

• Severe insulin deficiency.
• Abrupt onset of severe symptoms.
• Tendency to ketosis and
• Dependency on exogenous insulin to sustain life

Causes of Type 1 Diabetes or IDDM :

• Genetic susceptibility: The genetic susceptibility to IDDM is conferred by genes constituting the HLA complex, located on the short arm of chromosome 6.
  
  
  This locus is referred to as IDDM or type 1 DM. The strongest association are with HLA class 2 antigens in the DR and DM regions. The possibility of heterogeneity within was suggested linked axes of susceptibility. Two subtypes of type 1 have been identified.
  Type 1a is more common and occurs predominantly in less than 30 years of age.
  
  
  The primary associations are particularly with HLA-DR4 and slightly more males are affected.
  Type 1b is less common, occurs mainly in women over 30 years and is primarily associated by HLA-DR3.
  It is well to remember that approximately 10% of those with type 1 DM also have other organ specific autoimmune disorders like Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease and pernicious anemia, thus suggesting a basic derangement of immuno-regulation.

• Environmental triggers: Epidemiological data provide evidence to link environmental triggers with type 1 DM.
  The most common viruses which can cause DM include Coxsackie’s group, rubella, measles, mumps and Epstein-Barr virus. Although most of these viruses directly attack B cells, they seldom cause total and complete destruction of these cells. The likely sequence of events initiated by virus infections include-
  1. Partial or mild B cell injury.
  2. Immune response against one or more antigens.
  3. Triggering of autoimmune process in those with HLA linked susceptibility.
  4. Progressive immune mediated inflammatory loss of B cells and
  5. Clinical onset of type 1 DM after a variable period of latency in some of these subjects.
  6. Vial infections in utero is consistent with the observation that incidence of type 1 DM is increased in children’s with congenital rubella.
• Recognized environmental factors other than viruses include chemicals and drugs as well as alterations in dietary constituents. Specific chemicals include alloxan and vacor (a rodenticide), while streptozotocin and pentamidine are used as drugs.
  Like viruses, these chemicals and drugs may act directly as betacytotoxic and in addition may also trigger an immune process.
  Exposure to nitrosamines (used in preservation of meat) in women at time of conception may increase risk of type 1 DM in the offspring, especially in male child.
  Diets deficient in certain essential fatty acids or with elevated n-6/n-3 ratio of poly-unsaturated fatty acids may alter the immune response, as does alteration in dietary protein; thus playing a role in the pathogenesis.

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