The causes of diabetes mellitus can be categorized under three headings: (i) the agent factor, (ii) the non modifiable or host factor and (iii) the modifiable or environmental factors.
First we will discus the first two causes i.e. agent factor and non modifiable or host factor.
(1) The Agent Factor:
The underlying cause of diabetes is insulin deficiency which is almost absolute in IDDM (insulin dependent diabetes mellitus) and partial in NIDDM (non insulin dependent diabetes mellitus). Insulin deficiency may be due to a wide variety of causes (i) pancreatic disorders, inflammatory, neoplastic and cystic fibrosis, (ii) defects in the formation of insulin molecule; (iii) decreased insulin sensitivity, due to decreased numbers of insulin receptors in target tissue (iv) destruction of beta cells of pancreas due to viral infections pancreatitis, (v) genetic defects, e.g., mutation of insulin gene; and (vi) autoimmune diseases. There is reduced utilization of glucose which leads to hyperglycemia (high glucose level in blood) accompanied by glycosuria (glucose in urine).
(2) The Non Modifiable or Host Factors:
Age: Diabetes can occur at any age, studies indicate that prevalence rises steeply with age. NIDDM usually comes to light in the middle years of life and thereafter begins to rise in frequency. The prognosis is worse in younger diabetics who develop complications earlier than older diabetics. IDDM can occur at any age.
Sex: In some countries (UK) the overall male-female ratio is about equal. In south-east Asia, male diabetics are more in number. But in general male female ratio is almost the same.
Genetic factors: The genetic nature of diabetes is undisputed. Twin studies showed that in identical twins who developed NIDDM, concordance was approximately 90 percent, which demonstrate a strong genetic component. In IDDM (type 1 diabetes), the concordance was only about 50 percent indicating that IDDM is not totally a genetic entity.
Genetic markers: IDDM is associated with HLA-B8 and HLA-B15, and more powerfully with HLA-DR3 and HLA-DR4. The highest risk of IDDM is carried by individuals with both DR3 and DR4. But NIDDM is not HLA-associated.
Immune mechanisms: There is some evidence of both cell-mediated and of humoral (antibody mediated) activity against beta cells of pancreas. Some people appear to have defective immunological mechanisms, and under the influence of some environmental ?trigger?, attack their own insulin producing cells.
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