Diabetes mellitus (DM) is a multisystem disease with both biochemical and structural consequences. 
It is a chronic disease of carbohydrate, fat and protein metabolism, resulting from an inadequate 
action of the hormone, insulin. 

Two main types of primary diabetes mellitus are identified, mainly on clinical
grounds Type I diabetes (insulin-dependent diabetes mellitus - IDDM,
or juvenile-onset diabetes), and Type II diabetes (non-insulin-dependent
diabetes - NIDDM, or maturity-onset diabetes).

Diabetes may also occur secondarily to generalized disease of the pancreas, e.g. 
chronic pancreatitis and haemochromatosis, or may be caused by the secretion of 
hormones which antagonize the effects of insulin,e.g. in Cushing's syndrome and 
acromegaly; such diabetes is called secondary diabetes mellitus.

Type I diabetes is an organ-specific autoimune disease

As one of its synonyms implies, Type I diabetes usually presents in childhood
or adolescence, mainly as a result of the biochemical disorders leading to 
hyperglycaemia and diabetic ketoacidosis.
This type of diabetes is an autoimmune phenomenon; the majority of patients have 
circulating antibodies to the endocrine-cellpopulation of the islet
 cells of the pancreas, including antibodies against the insulin-secreting cells.
It is therefore an example of an organ-specific autoimmune disease. 

The pancreas in Type I diabetes shows lymphocytic infiltration and destruction
of the insulin-secreting cells of the islets of Langerhans. This destruction of
insulin-secreting cells leads to an insulin deficiency, which in turn leads to 
hyperglycaemia and other secondary metabolic complications.
Type II diabetes is the result of insulin resistance in peripheral tissues

Type II diabetes is four or five times more common than Type I diabetes.

Unlike Type I diabetes, where there is an absolute absence of insulin, 
In Type II diabetes the blood insulin levels are initially normal,
or may even increase in the early stages, before falling eventually to below normal.
The defect in the Type II pattern is a combination of the effects of the relative
deficiency of insulin when compared to the need, and the phenomenon of insulin 
resistance, in which the tissues are unable to respond to insulin. Insulin resistance
is thought to be due to an impairment of the function of receptors for insulin on 
the surfaces of target cells, meaning that glucose does not enter the cell. 

A protein called amylin is produced in the insulin-secreting cells of the pancreatic
islets, and is secreted with the insulin. 
In Type II diabetics, this protein accumulates in excess around the 
pancreatic islet cells, producing an amorphous deposit of material with the
characteristics of amyloid Its role is not understood,but it may interfere
with the subsequent secretion of insulin by the islet cells.

Morbidity and mortality in diabetes mellitus is now mainly the result of its 
structural complications

Whereas in former years the biochemical disturbances in diabetes mellitus usually 
led to an early death, the development of insulin treatment for Type I diabetes and
of various oral hypoglycaemic agents (when combined with diet) for Type II diabetes,
have greatly reduced mortality due to hyperglycaemia, hypoglycaemia and the 
complications of ketoacidotic coma. 
Nevertheless, diabetes remains an important cause of morbidity
and mortality due to a series of common complications.
The major complications of diabetes are:
  • Predisposition to infection.
  • Increased severity of atherosclerosis and its complications.
  • Extensive small vessel disease (arteriolosclerosis).
  • Renal glomerular disease.
  • Retinal vascular disease.
  • Peripheral nerve damage.
As a result of these complications, diabetics of both types have a predisposition
to develop ischaemic heart disease, cerebrovascular disease, peripheral gangrene
of lower limbs, chronic renal disease, reduced visual acuity leading to blindness,
and peripheral neuropathy.
 
The most important complications are vascular disease, renal disease, and eye disease.

Diabetics are particularly prone to infection

Patients with diabetes have an increased tendency to develop infections, usually 
of a bacterial or fungal nature. The main target organs are the skin, the oral and
genital mucosae, and the urinary tract.

In the skin, diabetics are particularly vulnerable to follicular infections by 
staphylococci, and the lesions tend to be more severe than in non-diabetics; boils 
are particularly frequent in Type II elderly diabetics. 
Other skin conditions that are more common 
in diabetics are superficial fungal infections, cellulitis and erysipelas. 

Diabetics may have particularly severe oral or genital mucosal infections.

In the kidney, in addition to the other abnormalities due to small and large 
vessel disease, there is an increased predisposition to acute pyelonephritis,
often associated with recurrent lower urinary tract infections, and sometimes 
complicated by papillary necrosis.

Diabetics have very severe atherosclerosis.

Although atherosclerosis is widespread and common, diabetics in general suffer 
much more severe and extensive atherosclerosis than non-diabetics of the same age and gender.
Furthermore, in diabetics the atherosclerotic changes extend into much smaller artery 
branches than in the non-diabetic. 
The main clinical sequelae of this are seen in:
  

 • The heart, where coronary atherosclerosis is more severe and extensive than in non-diabetics, 
   predisposing to ischaemic heart disease.
 • The brain, where atherosclerosis of the internal carotid and vertebrobasilar arteries and their
   branches predisposes to cerebral ischaemia.
 • The legs and feet, where severe atherosclerosis of the iliofemoral and smaller arteries in 
   the lower leg predisposes to the development of gangrene. Ischaemia of a single toe, or 
   ischaemic areas on the heel, are characteristic features of diabetic gangrene, which is 
   due to the involvement of smaller, more peripheral arteries than is the case in non-diabetic 
   generalized atherosclerosis.
 • The kidney, where extension of atherosclerosis into the main renal arteries and their 
   intrarenal branches makes a major contribution towards chronic nephron ischaemia, an important
   component of the multiple renal lesions in diabetes.

Microvascular disease is an important feature of diabetes, and is responsible for
many of the pathological complications

Small arterioles and capillaries in diabetes show a characteristic pattern of wall thickening,
which is due to a marked expansion of the basement membrane, termed hyaline arteriolosclerosis.
This small vessel abnormality is widespread, and is responsible for ischaemic changes 
which are symptomatic in the kidney, the retina, the brain and in peripheral nerves.

In the kidney, the capillaries of the glomerular tuft show marked basement membrane
thickening associated with increased leakiness of the capillary wall. 
This permits the leakage of plasma proteins into the glomerular filtrate in amounts greater
than can be reabsorbed in the tubular part of the nephron, leading to proteinuria,
and eventually glomerular hyalinization with development of chronic renal failure .

In the retina, the vessel wall changes lead to retinal haemorrhage and vascular proliferation.
In the brain, the small vessel lesions lead to lacunar infarction and ischaemic 
white matter degeneration. In peripheral nerves, the capillary wall changes are 
believed to be a major factor in the development of peripheral neuropathy.
Diabetes is an important cause of acquired blindness in the Western World.

Diabetes can affect the eyes in five main ways:

1 Background retinopathy is due to small vessel abnormalities in the retina leading to hard exudates, 
  haemorrhages and microaneurysms; this does not usually affect acuity.

2 Proliferative retinopathy is caused by the extensive proliferation of new small blood vessels 
  in the retina. 
  Sudden deterioration in vision can result from vitreous haemorrhage from the proliferating 
  new vessels or the   development of retinal detachment.

3 Maculopathy is caused by oedema, hard exudates or retinal ischaemia, and causes marked reduction
  in Acuity.

4 Cataract formation is greatly increased in diabetics.

5 Glaucoma shows an increased incidence in diabetics due to neovascularization of the iris, 
  rubeosis iridis.