DIABETES MELLITUS

Diabetes Mellitus (DM) is defined as a metabolic disorder characterized by common feature of chronic
hyperglycemia with disturbance in carbohydrate, fat and protein metabolism.

INSULIN: Insulin is a polypeptide hormone produced by the β-cells of islets of Langerhans of the
pancreas. It plays a key role in carbohydrate, lipid and protein metabolisms.
 It lowers blood glucose levels by increasing glucose uptake and utilization by the cells.
 It decreases gluconeogenesis in the body.
 It enhances protein and fatty acid synthesis in the tissues.

Classification based on etiology:

Based on the cause, DM is classified into 4 types:

1) TYPE 1 DM: It constitutes 10% of the cases of DM. It is also called insulin-dependent diabetes
mellitus (IDDM) because patients require insulin replacement as treatment. It was previously
also known as juvenile-onset diabetes (JOD) due to its occurrence in younger age, however its is
now known that it can occur at any age.
Based on the etiology, type 1 DM is further divided into 2 subtypes:
Subtype 1A (immune mediated) DM: characterized by autoimmune destruction of β-cells which
leads to insulin deficiency.
Subtype 1B (idiopathic) DM: characterized by insulin deficiency with tendency to develop
ketosis but these patients are negative for autoimmune markers.
The basic phenomenon in type 1 DM is the destruction of β-cell mass, leading to insulin
deficiency.

2) TYPE 2 DM: It accounts for about 80% of DM cases. It was earlier known as maturity onset
diabetes (MOD) or non-insulin dependent diabetes mellitus (NIDDM) of obese and non-obese
type. However it is now known that it also occurs in obese adolescent children hence the term
MOD is inappropriate. Moreover, many type 2 DM patients require insulin therapy to control
hyperglycemia or to prevent ketosis and thus are not truly non-insulin dependent contrary to
older nomenclature.
Type 2 DM is due to impaired insulin secretion or insulin resistance i.e. the cells don’t respond
well to insulin.

3) OTHER SPECIFIC ETIOLOGIC TYPES OF DM: It accounts for about 10% of the DM cases. Here DM
is due to the following causes:
 Genetic defect of β-cell function
 Genetic defect in insulin function
 Diseases of exocrine pancreas (e.g. Chronic pancreatitis, pancreatic tumors)
 Drug or chemical induced (e.g. steroids, thyroid hormones, β-blockers etc.)
  Infections
 Other genetic syndromes( e.g. down’s syndrome, Klinefelter’s syndrome, Turner’s
syndrome)
 Endocrinopathies (e.g. Cushing’s syndrome, acromegaly etc.)

4) GESTATIONAL DIABETES MELLITUS: About 4% of pregnant women develop DM due to

metabolic changes during pregnancy. Although they revert back to normal glycaemia after
delivery, these women are prone to develop DM later in life.

PATHOGENESIS
PATHOGENESIS OF TYPE 1 DM: The pathogenesis of type 1B DM is idiopathic, while pathogenesis of
type 1A DM is immune mediated and is based on the following factors:
 Genetic susceptibility: Type 1A DM can be developed by inheritance of certain susceptibility
genes located on chromosome no. 6.
 Autoimmunity: Destruction of β-cells by the immune cells of the body.
 Environmental factors: Certain viral infections or chemicals are known to induce type 1A DM.

PATHOGENESIS OF TYPE 2 DM:

A number of factors are associated with the development of type 2 DM :
 Genetic factors: A person having parents who have diabetes are at an increased risk of getting
diabetes.
 Constitutional factors: Factors such as obesity, hypertension, low level of physical activity.
 Insulin resistance: Resistance to insulin impairs glucose uptake and utilization and hence
hyperglycemia. There is also increased gluconeogenesis in the body.
 Impaired insulin secretion: Failure of β-cell function to secrete adequate insulin. The exact
genetic mechanism of this fall in insulin secretion is however unclear.

METABOLIC CHANGES AND COMPLICATIONS IN DIABETES

Diabetes mellitus causes various biochemical and structural alterations which can lead to several
complications such as:
 Diabetic ketoacidosis: It is the excess buildup of ketone bodies in the blood.
 Glucose toxicity: Hyperglycaemia can have harmful osmotic effects causing dehydration due
to increased urine output. Prolonged hyperglycemia can damage the blood vessels,nerves
and kidneys.
 High blood pressure
 Hyperlipidaemia which leads to the development of Atherosclerosis i.e, the
thickening/hardening of blood vessels due to the accumulation of lipids.
 Infections: Diabetics are shown to have increased susceptibility to various infections as well
as ulcerations.
 LABORATORY DIAGNOSIS
Hyperglycaemia remains the fundamental basis for the diagnosis of diabetes mellitus.
The following investigations are helpful in establishing the diagnosis of DM:
 URINE TESTING: In DM there is an increased excretion of glucose and ketone bodies in the
urine. Urine is tested for the presence of glucose by Benedict’s qualitative test and dipstick
method and for ketones by Rothera’s and strip test.
 BLOOD GLUCOSE/SUGAR TEST: By glucometer, semi-autoanalyser or autoanalyser. A
fasting blood glucose of about 126mg/dl and higher is an indicative of diabetes.
 GLYCOSYLATED HAEMOGLOBIN(HbA1C) TEST: Glucose levels in blood often varies due to
dietary intake the previous day thus long term assessment of blood glucose is done by
HbA1C test.
This test measures the average blood sugar level over the past 3 months.
 INSULIN ASSAY: Plasma insulin can be measured by radioimmunoassay and ELISA
technique. Its deficiency is an indicative of type 1 DM.

BOOK REFERENCES:

 Textbook of Pathology by HARSH MOHAN

 Textbook of Biochemistry by U.Satanarayana