COMPLIATIONS OF DIABETES.pdf microvascular and macrovascular complications reference from Harsh mohan textbook of pathophysiology

Various complications of diabetes such as microvascular and macrovascular are discussed

1. COMPLICATIONS OF
DIABETES

2. DEFINITION
As per the WHO, diabetes mellitus (DM) is defined as a heterogeneous
metabolic disorder characterised by common feature of chronic hyperglycaemia
with disturbance of carbohydrate, fat and protein metabolism.
ETIOLOGICAL CLASSIFICATION
I. TYPE 1 DIABETES MELLITUS (10%)
(earlier called Insulin-dependent, or juvenile-onset diabetes)
Type IA DM: Immune-mediated
Type IB DM: Idiopathic
II. TYPE 2 DIABETES MELLITUS (80%)
(earlier called non-insulin-dependent, or maturity-onset diabetes)
III. OTHER SPECIFIC TYPES OF DIABETES (10%)
Genetic defects, Diseases of exocrine pancreas, Drug- or chemical-induced, immune-
mediated DM
IV. GESTATIONAL DIABETES MELLITUS

3. COMPLICATIONS OF DIABETES
▪In both type 1 and 2 DM, severity and chronicity of
hyperglycaemia forms the main pathogenetic mechanism for
Microvascular complications:
Retinopathy, Nephropathy, Neuropathy
▪Longstanding cases of type 2 DM, develop ‘
Macrovascular complications:
Atherosclerosis, Coronary artery disease, Peripheral
vascular disease, Cerebrovascular disease

5. LONG TERM COMPLICATIONS OF DIABETES

6. Both types of diabetes mellitus may develop complications which
are broadly divided into 2 major groups:
I. Acute metabolic complications: These include diabetic
ketoacidosis, hyperosmolar nonketotic coma, and
hypoglycaemia.
II. Late systemic complications: These are atherosclerosis,
diabetic microangiopathy, diabetic nephropathy, diabetic
neuropathy, diabetic retinopathy and infections.

7. I.ACUTE METABOLIC COMPLICATIONS:
Metabolic complications develop acutely. While ketoacidosis
and hypoglycaemic episodes are primarily complications of
type1 DM
Hyperosmolar nonketotic coma is chiefly a complication of
type 2 DM
1. Diabetic ketoacidosis (DKA)
• Ketoacidosis is a complication of type 1
DM.
• It can develop in patients with severe insulin deficiency
combined with glucagon excess. Failure to take insulin and
exposure to stress are the usual precipitating causes.

8. •Severe lack of insulin causes lipolysis in the adipose tissues,
results in release of free fatty acids into the plasma.
•These free fatty acids are taken up by the liver where they are
oxidised through acetyl coenzyme-A to ketone bodies,
(acetoacetic acid and β-hydroxybutyric acid)
•Such free fatty acid oxidation to ketone bodies is accelerated in
the presence of elevated level of glucagon.
•Once the rate of ketogenesis exceeds the rate at
which the ketone bodies can be utilised by the muscles and
other tissues, ketonaemia and ketonuria occur.
•If urinary excretion of ketone bodies is prevented due to
dehydration, systemic metabolic ketoacidosis occurs.
•Clinical presentations: anorexia, nausea, vomitings,
deep and fast breathing, mental confusion and coma.

10. 2. Hyperosmolar hyperglycaemic nonketotic coma (HHS)
•It is a complication of type 2 DM
•It is caused by severe dehydration resulting from sustained
hyperglycaemic diuresis.
•The loss of glucose in urine is so intense that the patient is unable
to drink sufficient water to maintain urinary fluid loss.
•Prominent central nervous signs are seen, which includes
Nausea, vomiting, drowsiness and eventually coma.
•Blood sugar is extremely high and plasma osmolality is high.
Thrombotic and bleeding complications are frequent due to high
viscosity of blood.
•The mortality rate in hyperosmolar nonketotic coma is high.

12. 3. Hypoglycaemia
•It may develop in patients of type 1 DM .
•It may result from excessive administration of insulin, missing
a meal, or stress.
•Hypoglycaemic episodes are harmful as they produce
permanent brain damage, or may result in worsening of
diabetic control and rebound hyperglycaemia, so called
Somogyi’s effect.

13. II. LATE SYSTEMIC COMPLICATIONS
• A number of systemic complications may develop after a period
of 15-20 years in either type of diabetes.
•Late complications are largely responsible for morbidity and
premature mortality in diabetes mellitus.
1. Atherosclerosis
• Atherosclerotic lesions appear earlier than in the general
population, are more extensive, and more often associated with
complicated plaques such as ulceration, calcification and
thrombosis.
•The cause for this accelerated atherosclerotic process is not
known but possible factors are
Hyperlipidaemia, reduced HDL levels, nonenzymatic
glycosylation, increased platelet adhesiveness, obesity and
associated hypertension in diabetes.

14. Ill-effects of accelerated atherosclerosis in diabetes are early onset
of :
oCoronary artery disease
oSilent myocardial infarction
oCerebral stroke
oGangrene of the toes and feet
Gangrene of the lower extremities is 100 times more common in
diabetics than in non-diabetics

15. 2. Diabetic microangiopathy
•Microangiopathy of diabetes is characterised by basement
membrane thickening of small blood vessels and capillaries of
different organs and tissues such as the skin, skeletal muscle, eye
and kidney.
•Similar type of basement membrane-like material is also
deposited in nonvascular tissues such as peripheral nerves, renal
tubules and Bowman’s capsule.
•The pathogenesis of diabetic microangiopathy and peripheral
neuropathy in diabetics is believed to be due to recurrent
hyperglycaemia that causes increased glycosylation of
haemoglobin and other proteins (e.g. collagen and basement
membrane material) resulting in thickening of basement
membrane.

16. 3. Diabetic nephropathy
•Renal involvement is a common complication and a leading
cause of death in diabetes.
•Four types of lesions are described in diabetic nephropathy
.
i) Diabetic glomerulosclerosis which includes diffuse and
nodular lesions of glomerulosclerosis.
ii) Vascular lesions that include hyaline arteriolosclerosis of
afferent and efferent arterioles and atheromas of renal
arteries.
iii) Diabetic pyelonephritis and necrotising renal papillitis.
iv) Tubular lesions or Armanni-Ebstein lesion.

17. 4. Diabetic neuropathy
•Diabetic neuropathy may affect all
parts of the nervous system but symmetric peripheral
neuropathy is most characteristic.
•Pathologic changes include segmental demyelination,
Schwann cell injury and axonal damage.
•The pathogenesis of neuropathy is not clear but it may be
related to diffuse microangiopathy , or may be due to
accumulation of sorbitol and fructose as a result of
hyperglycaemia, leading to deficiency of myoinositol.
.

18. 5. Diabetic retinopathy
•Diabetic retinopathy is a leading cause of blindness.
•Besides Retinopathy, diabetes also predisposes the patients to
early development of cataract and glaucoma.

20. 6. Infections.
Diabetics have enhanced susceptibility to various infections such
as tuberculosis, pneumonias, pyelonephritis, otitis, carbuncles
and diabetic ulcers. This could be due to various factors such as
impaired leucocyte functions, reduced cellular immunity, poor
blood supply due to vascular involvement and hyperglycaemia.

21. REFERENCE
Harsh Mohan – Textbook of Pathology
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