Complications of diabetes mellitus
a) Diabetic ketosis and coma:
This is most common in the juvenile-onset type of the disease, and may be precipitated by the patient's
failure to administer his or her insulin. Vomiting and abdominal pain may be sever enough to simulate an
abdominal emergency.
b) Hyperosmolar non-ketogenic coma:
This condition is generally encountered in patients with maturity-onset diabetes, and may be precipitated
by an acute illness, such as an infection or a myocardial infarct. The plasma glucose level is over 33 mmol/l
(600 mg/dl), and may exceed 55 mmol/l (1000 mg/dl).
This leads to an increase in plasma osmolality. The osmotic diuresis that the severe hyperglycaemia
engenders leads to hyponatraemia and hypovolaemic shock. The effect of the dehydrations is most marked
on the central nervous system coma is characteristic, and fits occur in about one-third of cases. Ketosis is
not a feature of this condition, the precise pathogenesis of which is not known.
c) Cardiovascular disease:
There is good evidence that diabetics are more prone than normal people of the same age group to
develop atherosclerosis, peripheral vascular disease, gangrene of the toes and feet, and ischaemic heart
disease. This tendency does not seem to be related to the severity of the diabetes nor to the efficiency of
the treatment; indeed, treatment with tolbutamide and phenformin may actually increase the mortality
from cardiovascular disease.
The pathogenesis of the arterial disease in diabetes is poorly understood; a greater incidence of systemic
hypertension, microangiopathy of the vasa vasorum, obesity, and hypertriglyceridaemia (particularly an
elevated very low-density lipoprotein level) may all be relevant factors. The hypoxia that these vascular
lesions engenders may be aggravated by changes in the chemistry of the haemoglobin that occurs in severe
diabetes mellitus.
d) Hematological changes:
The increased formation of HbAic. Many abnormalities in polymorphs have been described, e.g. defects of
adherence, random migration, chemotaxis, phagocytosis and killing. Lymphocyte abnormalities have also
been noted, and the combined effect of these may well be to increase the susceptibility to infection.
Nevertheless, the precise relationship of these in vitro findings to the clinical manifestations of diabetes
mellitus is not known.
e) Diabetic microangiopathy:
A thickening of the basement membrane of capillaries has been described in the skin, muscles, kidney,
retina, and other parts of the body. This change may be present before the onset of clinical diabetes, and
it has been suggested that this is the primary lesion of the common type of the disease. However, it is
more probably an effect of the low insulin level or the hyperglycaemia, since the changes have also been
described in the diabetes secondary to pancreatic destruction. The effects of the microangiopathy are
particularly important in the kidney, the retina and the nerves.
f) Diabetic nephropathy:
The common diffuse glomerulosclerosis involves thickening of the basement membrane of the glomerular
vessels together with mesangial proliferation and an increase in the amount of basement-membrane-like
material in the mesangium (Figure:5.A).
The most characteristic change is, however, nodular glomerulosclerosis, described by Kimmelstiel and
Wilson. In this there are focal depositions of basement-membrane-like material in the peripheral parts of
the glomeruli, thereby forming nodules of varying size
Diabetic nephropathy. A: Diffuse glomerulosclerosis. There is considerable mesangial proliferation and
thickening. B: Nodular glomeruloscle-rosis. There are focal accumulations of hyaline material disposed
especially in the peripheries of the glomerulus.
These nodules stain strongly by the PAS method. They contain collagen in which there is an abnormally
high degree of glycosylation of hydroxylysine residues as compared with normal basement membrane
collagen.
The kidney in diabetes mellitus shows other changes. There is often well-marked hyaline, PAS-positive
thickening of the afferent arterioles with ischaemic glomerular changes (Figure: 6.C). The exudative lesion
consists of deposits of fibrin on the glomeruli beneath the podocytes (fibrin caps) as well as beneath the
epithelial lining of the parietal layer of Bowman's capsule.
If glycosuria is present, the cytoplasm of the cells of the proximal convoluted tubules may be vacuolated
due to the accumulation of glycogen in them (the Armanni-Ebstein lesion).
Urinary tract infection is common in diabetic subjects, especially women, and papillary necrosis may occur;
clinically this is characterized by haematuria and the rapid onset of renal failure.
Diabetic nephropathy. C: Hyaline change of the afferent arteriole.
D: Capsular drop. This is an exudative lesion consisting of adeposit of fibrin beneath the epithelial lining of
Bowman's Capsule.
Glomerulosclerosis itself leads to proteinuria which may be of sufficient intensity to produce the nephritic
syndrome. In the terminal stages, nitrogen retention and renal failure occur.
g) Impotence:
It's occur due to diabetic neuropathy or blood vessel blockage.
Impotence afflicts approximately 13% of men who have type I diabetes and 8% of men who have type II
diabetes.
h) Diabetic foot:
Foot problems in diabetes cause more inpatient hospital bed occupancy than all the other medical
problems put together. They may be, at least in part, preventable by education. Foot ulcers can be divided
into three categories. Classical neuropathic ulceration occurs on the sole of the foot.
The ulcers can be deep but are usually painless. Ischaemic ulcers are classically painful, usually occur on the
distal ends of the toes, and are associated with signs of peripheral vascular disease and ischaemia. The
most common lesions are infected foot ulcers. There are usually a number of factors involved: vascular
disease, neuropathy, poor foot care and poorly controlled diabetes.
i) Dyslipidemia :
General principles:
Diabetes increases the risk for atherosclerotic vascular disease. This risk is greatest in people who have
other known risk factors, such as dyslipidemia, hypertension, smoking, and obesity. Furthermore, in type II
diabetes there is an additional increased risk for obesity and lipid abnormalities independent of the level of
glycemic control. A common abnormal lipid pattern in such patients is an elevation of VLDL, a reduction in
HDL, and an LDL fraction that contains a greater proportion small, dense LDL particles. Recent studies have
shown Lp(a) to be a significant independent risk factor for assessing CHD.
j) Changes in the eye:
The small retinal vessels show thickening of their basement membranes and luminal narrowing, which leads
to ischaemic changes in the retina. Focal dilatations of the vessels lead to the formation of
microaneurysms, which completes the picture of diabetic retinopathy.
Bleeding may occur into the vitreous, and when the haematoma organizes, the fibrous tissue that forms
undergoes contracture. This condition is called retinitis proliferans, and results in retinal detachment.
Vascularisation of the iris occurs by a similar mechanism (rubeosis iridis).
Cataract formation is another important complication of diabetes; it is little wonder that the disease is one
of the leading causes of blindness in the world.
k) Changes in the nerves:
The microangiopathy causes ischaemic changes in the peripheral nerves, thus producing the common
peripheral polyneuropathy of diabetics. The axons of the sensory nerves 'die back' from the periphery; that
is, degeneration begins in the distal portions of the axons and gradually spreads more proximally.
This results in a symmetrical loss of sensation of the hands and feet, giving the so-called stocking-and-glove
effect. There is loss of sensation, which paradoxically is sometimes associated with spontaneous pain. The
lack of pain sensation in the feet can lead to unnoticed injuries. Infection and gangrene can then follow.
The polyneuropathy seen in diabetes mellitus is very similar to that of alcoholism, nutritional deficiencies,
and uraemia.
Sometimes the neuropathy affects one nerve, and this is presumably the result of ischaemic damage of a
more localized nature. Neuropathy affecting the autonomic nervous system can lead to many diverse
effects. When affecting the gut it may malabsorption syndrome.
Difficulty in emptying the bladder can be another effect and contributes to urinary tract infection. Other
symptoms include postural hypotension, loss of sweating of the feet and impotence.
l) Skin changes:
Apart from the effects of infection and ischaemia, several characteristic lesions may occur: necrobiosis
lipoidica, widespread granuloma annular, and eruptive xanthomas are characteristic. Diabetic dermopathy
consists of atrophic brown lesions, generally on the lower leg; they are probably of ischaemic origin.
m) Liability to infection:
Diabetic subjects are particularly liable to recurrent infections of various types. These may be pyogenic,
and skin infections such as recurrent boils should alert one to the possibility of underlying diabetes
mellitus.
Recurrent cystitis, particular in women, is common, as is candidal vaginitis. This infection is one of the
causes of pruritis vulvae, a common complaint of patients with diabetes. It is an old observation that
diabetics are particularly susceptible to tuberculous infection of the lungs. The mechanism of these
susceptibilities is not known.
a) Diabetic ketosis and coma:
This is most common in the juvenile-onset type of the disease, and may be precipitated by the patient's
failure to administer his or her insulin. Vomiting and abdominal pain may be sever enough to simulate an
abdominal emergency.
b) Hyperosmolar non-ketogenic coma:
This condition is generally encountered in patients with maturity-onset diabetes, and may be precipitated
by an acute illness, such as an infection or a myocardial infarct. The plasma glucose level is over 33 mmol/l
(600 mg/dl), and may exceed 55 mmol/l (1000 mg/dl).
This leads to an increase in plasma osmolality. The osmotic diuresis that the severe hyperglycaemia
engenders leads to hyponatraemia and hypovolaemic shock. The effect of the dehydrations is most marked
on the central nervous system coma is characteristic, and fits occur in about one-third of cases. Ketosis is
not a feature of this condition, the precise pathogenesis of which is not known.
c) Cardiovascular disease:
There is good evidence that diabetics are more prone than normal people of the same age group to
develop atherosclerosis, peripheral vascular disease, gangrene of the toes and feet, and ischaemic heart
disease. This tendency does not seem to be related to the severity of the diabetes nor to the efficiency of
the treatment; indeed, treatment with tolbutamide and phenformin may actually increase the mortality
from cardiovascular disease.
The pathogenesis of the arterial disease in diabetes is poorly understood; a greater incidence of systemic
hypertension, microangiopathy of the vasa vasorum, obesity, and hypertriglyceridaemia (particularly an
elevated very low-density lipoprotein level) may all be relevant factors. The hypoxia that these vascular
lesions engenders may be aggravated by changes in the chemistry of the haemoglobin that occurs in severe
diabetes mellitus.
d) Hematological changes:
The increased formation of HbAic. Many abnormalities in polymorphs have been described, e.g. defects of
adherence, random migration, chemotaxis, phagocytosis and killing. Lymphocyte abnormalities have also
been noted, and the combined effect of these may well be to increase the susceptibility to infection.
Nevertheless, the precise relationship of these in vitro findings to the clinical manifestations of diabetes
mellitus is not known.
e) Diabetic microangiopathy:
A thickening of the basement membrane of capillaries has been described in the skin, muscles, kidney,
retina, and other parts of the body. This change may be present before the onset of clinical diabetes, and
it has been suggested that this is the primary lesion of the common type of the disease. However, it is
more probably an effect of the low insulin level or the hyperglycaemia, since the changes have also been
described in the diabetes secondary to pancreatic destruction. The effects of the microangiopathy are
particularly important in the kidney, the retina and the nerves.
f) Diabetic nephropathy:
The common diffuse glomerulosclerosis involves thickening of the basement membrane of the glomerular
vessels together with mesangial proliferation and an increase in the amount of basement-membrane-like
material in the mesangium (Figure:5.A).
The most characteristic change is, however, nodular glomerulosclerosis, described by Kimmelstiel and
Wilson. In this there are focal depositions of basement-membrane-like material in the peripheral parts of
the glomeruli, thereby forming nodules of varying size
Diabetic nephropathy. A: Diffuse glomerulosclerosis. There is considerable mesangial proliferation and
thickening. B: Nodular glomeruloscle-rosis. There are focal accumulations of hyaline material disposed
especially in the peripheries of the glomerulus.
These nodules stain strongly by the PAS method. They contain collagen in which there is an abnormally
high degree of glycosylation of hydroxylysine residues as compared with normal basement membrane
collagen.
The kidney in diabetes mellitus shows other changes. There is often well-marked hyaline, PAS-positive
thickening of the afferent arterioles with ischaemic glomerular changes (Figure: 6.C). The exudative lesion
consists of deposits of fibrin on the glomeruli beneath the podocytes (fibrin caps) as well as beneath the
epithelial lining of the parietal layer of Bowman's capsule.
If glycosuria is present, the cytoplasm of the cells of the proximal convoluted tubules may be vacuolated
due to the accumulation of glycogen in them (the Armanni-Ebstein lesion).
Urinary tract infection is common in diabetic subjects, especially women, and papillary necrosis may occur;
clinically this is characterized by haematuria and the rapid onset of renal failure.
Diabetic nephropathy. C: Hyaline change of the afferent arteriole.
D: Capsular drop. This is an exudative lesion consisting of adeposit of fibrin beneath the epithelial lining of
Bowman's Capsule.
Glomerulosclerosis itself leads to proteinuria which may be of sufficient intensity to produce the nephritic
syndrome. In the terminal stages, nitrogen retention and renal failure occur.
g) Impotence:
It's occur due to diabetic neuropathy or blood vessel blockage.
Impotence afflicts approximately 13% of men who have type I diabetes and 8% of men who have type II
diabetes.
h) Diabetic foot:
Foot problems in diabetes cause more inpatient hospital bed occupancy than all the other medical
problems put together. They may be, at least in part, preventable by education. Foot ulcers can be divided
into three categories. Classical neuropathic ulceration occurs on the sole of the foot.
The ulcers can be deep but are usually painless. Ischaemic ulcers are classically painful, usually occur on the
distal ends of the toes, and are associated with signs of peripheral vascular disease and ischaemia. The
most common lesions are infected foot ulcers. There are usually a number of factors involved: vascular
disease, neuropathy, poor foot care and poorly controlled diabetes.
i) Dyslipidemia :
General principles:
Diabetes increases the risk for atherosclerotic vascular disease. This risk is greatest in people who have
other known risk factors, such as dyslipidemia, hypertension, smoking, and obesity. Furthermore, in type II
diabetes there is an additional increased risk for obesity and lipid abnormalities independent of the level of
glycemic control. A common abnormal lipid pattern in such patients is an elevation of VLDL, a reduction in
HDL, and an LDL fraction that contains a greater proportion small, dense LDL particles. Recent studies have
shown Lp(a) to be a significant independent risk factor for assessing CHD.
j) Changes in the eye:
The small retinal vessels show thickening of their basement membranes and luminal narrowing, which leads
to ischaemic changes in the retina. Focal dilatations of the vessels lead to the formation of
microaneurysms, which completes the picture of diabetic retinopathy.
Bleeding may occur into the vitreous, and when the haematoma organizes, the fibrous tissue that forms
undergoes contracture. This condition is called retinitis proliferans, and results in retinal detachment.
Vascularisation of the iris occurs by a similar mechanism (rubeosis iridis).
Cataract formation is another important complication of diabetes; it is little wonder that the disease is one
of the leading causes of blindness in the world.
k) Changes in the nerves:
The microangiopathy causes ischaemic changes in the peripheral nerves, thus producing the common
peripheral polyneuropathy of diabetics. The axons of the sensory nerves 'die back' from the periphery; that
is, degeneration begins in the distal portions of the axons and gradually spreads more proximally.
This results in a symmetrical loss of sensation of the hands and feet, giving the so-called stocking-and-glove
effect. There is loss of sensation, which paradoxically is sometimes associated with spontaneous pain. The
lack of pain sensation in the feet can lead to unnoticed injuries. Infection and gangrene can then follow.
The polyneuropathy seen in diabetes mellitus is very similar to that of alcoholism, nutritional deficiencies,
and uraemia.
Sometimes the neuropathy affects one nerve, and this is presumably the result of ischaemic damage of a
more localized nature. Neuropathy affecting the autonomic nervous system can lead to many diverse
effects. When affecting the gut it may malabsorption syndrome.
Difficulty in emptying the bladder can be another effect and contributes to urinary tract infection. Other
symptoms include postural hypotension, loss of sweating of the feet and impotence.
l) Skin changes:
Apart from the effects of infection and ischaemia, several characteristic lesions may occur: necrobiosis
lipoidica, widespread granuloma annular, and eruptive xanthomas are characteristic. Diabetic dermopathy
consists of atrophic brown lesions, generally on the lower leg; they are probably of ischaemic origin.
m) Liability to infection:
Diabetic subjects are particularly liable to recurrent infections of various types. These may be pyogenic,
and skin infections such as recurrent boils should alert one to the possibility of underlying diabetes
mellitus.
Recurrent cystitis, particular in women, is common, as is candidal vaginitis. This infection is one of the
causes of pruritis vulvae, a common complaint of patients with diabetes. It is an old observation that
diabetics are particularly susceptible to tuberculous infection of the lungs. The mechanism of these
susceptibilities is not known.
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Diabetes Mellitus
