DIABETES MELLITUS

The Pancreas is an exocrine as well as an endocrine gland. The exocrine portion

produces digestive enzymes & the endocrine portion produces hormones fro cells in the
islets of Langerhans:

 Alpha cells – produce Glucagon (that increases blood sugar levels)

 Beta cells – produce Insulin (that lowers blood sugar levels)
 Gamma cells – produce Somatostatin (Growth hormone antagonist)

Diabetes is disease due to relative or absolute deficiency of Insulin characterized by

polydipsia, polyphagia & polyuria. The blood sugar levels are high and there is
glycosuria. There are 4 types of Diabetes:

1. Type 1. Insulin dependent, i.e. the Pancreas does not produce any insulin at all.
2. Type 2. Non insulin dependent, some insulin is produce by the Pancreas but it is
not enough to ensure euglycaemia. This type can be treated by oral
hypoglycaemic agents.
3. Gestational diabetes. Appears only during pregnancy (not in between pregnancies)
4. Diabetes due to any other cause e.g. certain medication.

Type 1 Type 2
Age of onset Childhood or puberty Usually >35
Nutritional status at
Usually under nourished Usually obese
onset
Prevalence 5-10% 90-95%
Genetic
Moderate Very strong
predisposition
Beta cells are damaged but still
partly functional.
Defect/deficiency Beta cells are destroyed
May also be due to insulin
resistance
Note: Glycsylated Hb (HbA1c) levels give an indication of blood sugar control in the
previous 3 months.

Insulin: is a polypeptide. It is either obtained from animal sources or synthesised

from Escherichia coli using the DNA recumbent technology. It is administered by
subcutaneous or intravenous injection. It is destroyed by an enzyme called insulin
protease.

Adverse reactions: Hypoglycaemia either due to overdose or due to deficiency also

of countering hormones like glucagon, cortisol etc. Other effects include weight gain,
lipodystrophy & allergic rection at injection site.
 Types of insulin:

1. Rapid acting-regular or zinc insulin. They also have a short duration of action, so
less likely to produce hypoglycaemia. Can be given IV. Peak levels 30-90 minutes
2. Intermediate acting insulin. Called Neutral Protamine Hagedon (NPH). Is only
given SC (not IV), so not used in ketoacidosis.
3. Long acting insulins. Include Insulin glargine & Insulin detemir. Should be given
only SC (never IV), so not useful in ketoacidosis.
4. Insulin combinations. E.g those containing 70% NPH & 30% regular insulin are
also available.

Oral hypoglycaemic agents: Are used in Type 2 diabetes (never type 1), where the
Pancreas has some beta cell reserve to produce insulin, but diet control alone is not
sufficient. They Include:

1. Insulin secretagogues 4. Peptidase-IV inhibitors

2. Insulin sensitizers 5. Incretin mimetics
3. Glucosidase inhibitors

1. Insulin secretagogues: These include Sulphonylureas & Gliburides.

a. Sulfonylureas. Are effective for 12-24 hours.
Mech. Of action & uses
Stimulate insulin secretion from beta cells
of Pancreas
 by blocking K channels & causing Ca
influx
 decreasing glucose production
 increasing peripheral insulin
sensitivity
Adverse effects
 Nausea, GIT disturbance
 Weight gain
 Hypoglycaemia
 CVS
*Should be given carefully in Liver &
kidney disease as it is excreted by them, &
if diseased this can lead to accumulation in
the body& adverse effects.

Drugs reducing effect of Drugs potentiating effect of

Sulphonylureashyperglycaemia Sulphonylureashypoglycaemia
 Corticosteroids  Antidepressants like MAO inhibitors
 Sympathominmetics  Antibiotics like Sulphonamides &
 Phenothiazines Chloramphanicol
 Diuretics  Salisylates
 Niacin

b. Glinides. Are similar in action & adverse effects to Sulphonylureas but have
a shorter duration of action (are therefore called post prandial glucose
regulators). They should not be given together with Sulphonylureas because
they potentiate each others effect & may lead to hypoglycaemia).
 2. Insulin sensitizers
a. Biguanides. The only currently available one is Metformin.

Mech of action & uses Adverse effects

 Prevents gluconeogenesis  GIT upset
 Decreases glucose absorption from  CCF in cases of acute MI
intestine  Vit B12 absorption effected
 Increases glucose uptake by target cells
 Also reduces hyperlipidaemia (by
decreasing LDLs).
Weight loss occurs due to anorexia. Is also
useful in treating PCOD because it lowers
insulin resistance & so promotes ovulation

b. Tiazolidinediones (Glitazones): Available preparations are Pioglitazone &

Rosiglitazone.

Mech of action & uses Adverse effects

 Weight gain
Exact mechanism unclear. Require the  Worsening of heart failure
presence of insulin for their action.  Hepatotoxicity
Rosiglitazone increases LDL levels. Like
Metformin, it also promotes ovulation.