Chapter 23: Autoimmune diseases, Diabetes Mellitus Type 1
TYPE I (INSULIN DEPENDANT) DIABETES MELLITUS
Type I or insulin-dependent diabetes mellitus is a state of hyperglycemia because of a lack of insulin secretion from the b-cells in islets of Langerhan’s of the pancreas. These patients need exogenous insulin to sustain life.
It has a peak onset around puberty. In Europe, it is 5 to 43/100,000 populations per year, while in the USA 16 cases/100,000 per year.
Both sexes are equally affected.
Clinical Features (Signs & Symptoms)
- Glucose may be present in urine at the time of diagnosis (glycosuria).
- The patient may have prodromal symptoms of weight loss, thirst, polydipsia, and polyuria.
- Sometime patients may come with severe metabolic disturbance known as ketoacidosis coma.
Frequency of Type I diabetes mellitus:
90% of the cases are sporadic, while another remainder occurs within the family.
The relative risk in:
|HLA Typing||Relative Risk|
|HLA-Identical siblings of diabetic||44.0|
|Identical Twin of Diabetic||230.0|
Pathogenesis and Immunological Features
There are several hypotheses for the death of β-cell. The following two are more accepted.
- The presence of T-lymphocytes and selective loss of β-cells (insulin-producing) suggests targeting by T-cell receptor for β-cell-specific autoantigen. There is a predominance of CD8+ cells that suggests a cell-mediated cytotoxic reaction to damage β-cells.
- This hypothesis says that inflammatory cells infiltrate is not specifically against b-cell. The insulitis may be initiated by a viral infection, which may result in cytokines production, e.g. IL-1 is cytotoxic to b-cells. Macrophagic cells may produce IL-I. So if the macrophagic function is inhibited by treatment with silica diabetes does not develop in the experimental model.
- There is autoantibody against b-cells and these are present for several years before hyperglycemia appears.
- Using the human pancreas, an autoantibody binding to the islet cell cytoplasm (islet cell antibody = ICA) is detectable in some 75% of the patients at the time of diagnosis.
- Insulin autoantibody (IAA) appears before the start of treatment with insulin.
Islet cell-surface antibodies are detected but their role in the disease is not clear.
- Insulin at the physiologic level is needed.
- While for maturity-onset diabetes mellitus when there are no free receptors for insulin or decreased due to autoantibody, which binds to these receptors. So in these cases increase the amount of insulin is needed because it has to compete for available receptors.