Type 1 Diabetes

Type 1 A diabetes refers to diabetes brought on by autoimmune destruction of the pancreas. [1] There is a genetic susceptibility inherited by the presence of genes. However, diabetes does not develop in all offspring of those with type 1 diabetes. It is proposed that there must be a “second hit”, which starts the process of autoimmune attack on the pancreas.

Autoantibodies in Type 1 diabetes

Insulin associated antibodies

GAD 65 80%

Insulinoma associated protein -2   58%

Zinc Transporter protein 8 (ZnT8) 60 – 80%

Type 1 diabetes develops after the age of 6 months when the neonatal immune system matures. Other diagnoses have to be considered if the  diabetes presents before 6 months of age. (Transient neonatal diabetes). There is a biphasic peak in the incidence of diabetes with the larger peak in childhood, adolescence and early adulthood. There is a smaller peak in mid life which seems to be a slow burning autoimmune diabetes (LADA – Latent Autoimmune diabetes in Adults).  The early peak tends to be with patients who are very symptomatic with rapid onset and progression of diabetes, very often presenting with Diabetic keto-acidosis at diagnosis. Patients with LADA on the other hand tend to present with gradual onset and slow progression.  This is often initially diagnosed as Type 2 Diabetes and treatment is started with metformin. The diagnosis is often recognized when there is lack of response to  medications used for Type 2 Diabetes

MHC genes found on HLA region of chromosome 6p (short arm) are important in the development of type 1 Diabetes. These genes involve the presentation of antigens by APCs (antigen presenting cells)

HLA-DR3,DQB1*0201 (DR3-DQ2)  -DR4,DQB1*0302 ( DR4-DQ8) seem to be present in 90% of those with type 1 diabetes compared to 40% of controls. [2]. Although these genes are important, they do not seem to induce type 1 diabetes on its own and it is likely that there is a polygenic inheritance pattern leading to type 1 diabetes

Theories behind development of autoimmunity in Type 1 diabetes

  1. Molecular mimicry Coxackie Virus
  2. Delayed expression of protective protein  -loss of self tolerance [3]

 

 risk of developing  type 1 ԁiabetes [4]

No family history of Type 1 diabetes 0.4%

One parent with type 1 diabetes  – 6%

One sibling with type 1 diabetes  – 5%

Identical twin with type 1 diabetes – 50%

 

 

  1. The pathogenesis of insulin-dependent diabetes mellitus. Atkinson MA, Maclaren NK N Engl J Med. 1994;331(21):1428.
  2. High genetic risk for IDDM in the Pacific Northwest. First report from the Washington State Diabetes Prediction Study. Rowe RE, Leech NJ, Nepom GT, McCulloch DK Diabetes. 1994;43(1):87.
  3.  Studies on autoimmunity for initiation of beta-cell destruction. X. Delayed expression of a membrane-bound islet cell-specific 38 kDa autoantigen that precedes insulitis and diabetes in the diabetes-prone BB rat. Ko IY, Jun HS, Kim GS, Yoon JW Diabetologia. 1994;37(5):460.
  4. Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study. Redondo MJ, Rewers M, Yu L, Garg S, Pilcher CC, Elliott RB, Eisenbarth GS BMJ. 1999;318(7185):698.