AETIOLOGY AND CLASSIFICATION OF
• TYPE -1
• OTHER- genetic defects of insulin action,
pancreatic disease, hormonal antagonist to
insulin, drug induced, viral infections etc
• Duration of symptoms over
• Body wt- normal –low
• Ketonuria- +
• Autoantibodies +
• Family history -
• > 50yrs
• Duration of symptoms over
• • • +
ACTIONS OF INSULIN
• Carbohydrate metabolismGlucose transport,
• Lipid metabolismtriglyceride , fatty acids
• Protein metabolismAA transport, protein
• Fatty acid oxidation
• Protein degradation
HOW TO DIAGNOSE DM
Test for urine- glucose, ketones, proteins
Blood glucose- fasting and random
FBS- >7mmol/l (126mg/dl)
Glycosylated Hb- provides an accurate
measure of glycemic control over weeks to
B CELLS OF ISLET)
TRANSPORT OF GLUCOSE
INSULIN AND C
STRUCTURE OF INSULIN
• It comprises of 2 chains
• Joined by disulfide bonds.
• Porcine insulin resembles human insulin
except that is contains alanine residue on B
• Proinsulin has only mild biological activity
• Separate A & B chains are inactive.
• Elimination ½ - 5-10min ( iv adm)
• Metabolised into liver & kidneys by proteolytic
• 50% of insulin reaching liver is metabolized by its
single pass through liver.
• Renal dysfunctions prolongs its elimination.
• Its effect after iv adm- 30-60min
• Sc adm- released slowly as it tightly bound to
receptors so has a prolong effect.
• Insulin is secreted into the portal veins @
• Food intake increases the rate by 5-10 folds.
• Total daily secretion of insulin is 40U.
• Sympathetic and parasympathetic system
influence the secretion of insulin
• Ex: a-adrenergic stimulation-decreases
• b-adrenergic / parasym- increases.
• Receptors are characterized as insulin binding
• Contain 2 subunits( a & b) joined by disulfide
• Insulin & ATP( in vitro) receptors to become
phosphorylated on tyrosine residues of b
• The number of insulin receptors is inversely
proportional to its plasma conc.
• Insulin has an ability to regulate its receptorsobesity and IDDM – decrease in the receptors.
Source- bovine, porcine, human
Most common commercial preparation- 100U
Daily dose in DM- 20-60 U *
Biosynthetic and semisynthetic insulin
Semisynthetic(porcine) produced by
• Biosynthetic- recombinant DNA tec.
hours after sc adm
• Fast acting preparation
• Can be given iv/sc
• It can be mixed with other insulin preparation
in same syringe.
• t/t of abrupt onset hyperglycemia and
• Single iv-(5-10 U) OR infusion(0.5-2.0 U/h).
• It is intermediate acting
• Its duration of action is prolonged because it is
conjugated with protamine.
• It contains 0.005mg/U of protamine.
• NPH- neutral sol, protamine, origin in
• Long acting
• Larger particle size and crystalline form of
• Slow onset and prolonged duration of action
lacks its usefulness.
• Most serious side effect
• Pts vulnerable- receive insulin in absence of
• Symptoms-diaphoresis, taccy, hypertension,
mental confusion, seizures and coma.
• Rebound hyperglycemia can occur due to
sympath stimulation in response to
hypoglycemia ( somogyi effect).
• The diagnosis of hypoglycemia is difficult
during GA, ANS neuropathy, non selective b
blockers- signs are masked.
t/t of hypoglycemia
50-100 ml of 50% glucose solution-iv
s/e- nausea vomiting
• Local or systemic
• Local-erythematous indurated area, non
insulin materials in insulin prepations.
• Systemic-antibody mediated & can range from
urticaria to life threatening CVS collapse.
• Chronic exposure to NPH insulin may produce
antibodies against protamine
• Atrophy of fat at the sites of sc injections of
• t/t- frequently changing the site
Resistance to insulin
• It occurs in patients requiring > 100U of
• Acute or chronic
• Acute- trauma, surgery and infection
• Chronic –antibodies to insulin.
• ACTH, estrogens , glucagon
• Epinephrine inhibits insulin secretion and
• Guanethidine- reduces insulin requirements .
phenylbutazone,MAO-I increase the duration
of action of insulin.
• MOA- site of action is the receptors on islet of
• Inhibit ATP –sensitive K channels
depolarization of the cell membrane and
release of endogenous insulin.
Pharmacokinectics1. absorbed orally from GIT
2. Weakly acidic and bound to albumin(90-98%)
3. Metabolized in liver-active & inactive
4. Eliminated by kidneys- urine/feces
Tolbutamide1. shortest acting(6-12h)
3. El ½ -4-8h
4. causes fewest side effect
Duration-12-18h, el ½ -1.3-6h
Principle metabolite is
hydroxyhexamide it is 2.5
Not used in pts with renal
Uricosuric actions and its
used in pts with DM & gout
1. Duration-12-24h, el ½ -48h.
3. Highly absorb after oral
4. It produced active as well
as inactive products
excreted by kidneys
• Longest acting
• DOA-36h, el ½- 30-36h
• It produces disulfiram like
reactions & can cause
• DOA- 18-24h, el ½- 4-12 h
• Increases insulin sensitivity
and inhibit glucose
• Produces active and inactive
• It has mild diuretic effect.
• DOA-12-24h, el ½ - 4-7h
• It increases the glucose
uptake and inhibits its
• Produces inactive
• Mild diuretic effects.
• Most common- hypoglycemia but it is lesser
with 2nd generation.
• Renal dysfunction impair the elimination and
prolongs the effect- hypoglycemia
• Cross the placenta- fetal hypoglycemia
• Decrease blood glucose and produce low risk
• They decrease the lipid conc and can lead to
mild wt reduction in obese pts.
• PK- not bound to proteins and does not
• Excreted by kidneys (90%)
• It is used in cases when sulfonylureas have
• Peak plasma conc- 2, el ½- 2-4h
• It requires TDS administration
• MOA- stimulation of endogenous insulin
• Inhibits gluconeogenesis in kidneys and liver
and promotes uptake of glucose by skeletal
• it also decreases plasma conc of triglycerides
• Nausea ,diarrhea
• Lactic acidosis- binds to mitochondria
metabolises glucose anerobically
converts pyruvate to lactate
• Hypoxia and sepsis increase LA
INTESTINAL GLYCOSIDASE INHIBITORS
• Acarbose• Decreases carbohydrate digestion and absorption
• Used alone does not cause hypoglycemia
• It increases the effectiveness of injected insulin
• Its main effect is on postprandial glucose so it is
suited only as a adjunctive therapy
• High doses- hepatotoxicity.
• Bind to ppar (peroxisome proliferator activated
receptor) which regulates the expression of
• Enhance the endogenous insulin secretion.
• Drugs –rosiglitazone and pioglitazone
• Used as a 2nd line therapy for pts not responding
to metformin or sulponylurea.
• Also used in sever form of DM with obesity as
they redistribute abdominal fat to SC tissues
• S/E- hepatotoxicity and Na & water retention
MEGLITINIDES AND A.A DERIVATIVES
They are called as prandial glucose regulators
Drugs- repaglinide & nateglinide
Stimulates the endogenous insulin secretion
Adm immediately before meals.
Cause less hypoglycemia than sulfonylureas.
other forms of insulin
• Rapid acting insulin
Long acting insulin
• Davidsons- medicine
• Stoelting pharmacology