INSULIN AND ANTIDIABETIC

DRUGS

PROF.DR ASYA REHMAN

 PANCREATIC HORMONES:

 Insulin
 Glucagon
 Amylin
 Somatostatin
 Pancreatic peptide
 DIABETES MELLITUS

Diabetes mellitus may be defines as the elevated blood

glucose associated with absent or inadequate
pancreatic insulin secretion.

Classified into four categories:

1. Type1: Insulin-dependent diabetes
2. Type2: Non Insulin-dependent diabetes
3. Type3: Others
4. Type4: Gestational diabetes mellitus
 TYPE 1 DIABETES MELLITUS:
The hallmark of type 1 DM
 Selective beta cell destruction
 Severe or absolute insulin deficiency
Type 1 further subdivided into immune and
idiopathic causes
Immune form is the most common form, most patients are
younger than 30 yrs of age at the time of diagnosis but can
occur at any age.
In type1 DM insulin replacement therapy is necessary to sustain
life given by S/C injection or insulin infusion pump.
Interruption in the insulin replacement therapy can result in
diabetic ketoacidosis or death .
 TYPE 2 DIABETES MELLITUS:
 Characterized by tissue resistance to action of insulin
combined with relative deficiency of insulin.
 A person can have more beta cell deficiency or more
tissue resistance and abnormalities may be mild or
severe.
 Insulin is produced by pancreas but insufficient to
overcome the resistance and blood glucose rise.
The impaired insulin action also affects
 Fat metabolism, increased free fatty acid formation and
triglyceride levels and low levels of HDL.
 Ordinarily do not develop ketosis.. only in stress
such as inf. Or the use of medication that
enhances resistance e.g. corticosteroids.
LADA (latent autoimmune diabetes of adult)
 TYPE 3 DIABETES MELLITUS:

There are other multiple causes for the elevated

blood glucose.
- Pancreatectomy
 Pancreatitis
 Drug therapy

TYPE 4 DIABETES MELLITUS:

Gestational diabetes mellitus(GDM)

 INSULIN
 Insulin is a small protein produced by beta
cells of pancreatic islets. The entire human
pancreas contains up to 8mg of insulin.
INSULIN is secreted at low basal rate and higher
stimulated rate in response to variety of stimuli
especially GLUCOSE.
Other stimuli are:
 Sugars e.g. mannose
 Certain amino acids e.g. Lucien, arginine.
 Hormones such as glucagon like polypeptide (GLP-
1), glucagon, cholecytokinin and vagal activity.
INHIBITORY SIGNALS INCLUDE:
 Chronically elevated glucose level
 Somatostatin
 Chronically elevated levels of fatty acids

M.O.A OF RELEASE OF INSULIN:

 Hyperglycemia results in increase in intracellular
ATP levels, which closes the ATP dependant
potassium channels.
 Decrease efflux of potassium results in
depolarization of the beta cells.
 Opening of voltage gated Ca channels
 Increase in intracellular Ca triggers secretion of
hormone.
 INSULIN DEGRADATION: insulin is
removed by two main organs – liver and kidney

Liver clears 60% of endogenously released

insulin
Kidney removes 35-40% of hormone
However in insulin treated patients, this
ratio is reversed
Half-life is 3-5 min
Basal insulin values in normal humans are
5 – 15 uU/ml with peak rise of 60-
90uU/ml during meals

INSULIN RECEPTOR
EFFECTS OF INSULIN ON ITS TARGETS:

 Insulin promotes the storage of glucose

and fat (both sources of energy)

 Influence cell growth and metabolic

functions in wide variety of tissues.
ENDOCRINE EFFECTS OF INSULIN
 PRINCIPAL TYPES OF
INSULIN PREPARATIONS

 Four types of injected insulins are available:

1. RAPID ACTING
-Very fast onset and short duration
-3 types- insulin lispro, insulin aspart and insulin
glulisine- are commercially available
- Rapid acting insulin permits more physiologic prandial
replacement of insulin because of rapid onset and
reaches peak levels which closely resembles the normal
endogenous secretion of insulin than does regular
insulin.
 Can be given just before meal
 Duration of action is rarely more than 4 – 5 hrs
which decreases the risk of post meal
hypoglycemia.
 2. Short acting insulin
- Regular insulin is a short acting soluble crystalline zinc
insulin that is now made by recombinant DNA
techniques to produce a molecule identical to that of
human insulin.

 Its effect appears within 30 min and peaks between

2 – 3 hrs after S/C injection and lasts for about 5 –
8 hrs.
 Should be administered 30 – 45 min before meal to
prevent the rapid rise of glucose and post prandial
hypoglycemia.
 Regular short acting soluble insulin is the only type
that can be given I/V.
 Particularly useful in management of diabetic
ketoacidosis, and when insulin requirement is
changing rapidly e.g. acute infection and after
surgery
 3. Intermediate acting and long acting
insulins

1. NPH ( neutral protamine hagedron or isophane)

insulin. Onset is approx 2 – 5 hrs and duration of 4
– 12 hrs.
2. Insulin glargine
3. Insulin detimer

4. Mixtures of Insulin

- INSULIN PRODUCTIONS
 Human insulin
 Concentration
INSULIN DELIVERY SYSTEMS
- The standard mode of insulin therapy is by S/C inj
using conventional syringes and disposable needles
1. Portable pen injectors
2. Continuous subcutaneous insulin infusion
device
(CSII, insulin pumps)

- These devices has programmable pumps that

delivers individualized basal and bolus insulin
replacement doses based on glucose self monitoring
results.
- These devices are encouraged by people who are
unable to obtain target control when on multiple inj
and where excellent glycemic control is required e.g.
pregnancy
INSULIN REGIMENS
A. Intensive insulin therapy
- Prescribed for almost every one with type 1 DM
as well as with type 2 DM.
- In this regimen, the meal, snack or high sugar
level correction boluses are prescribed by
formulas to calculate the rapid acting insulin
bolus dose by considering that how much CHO
is in the meal, the formula for the meal or snack
is expresses as an insulin to carbohydrate
ratio which refers to how many grams
of carbohydrate will be disposed by 1
unit of rapid acting insulin.
CONVENTIONAL INSULIN THERAPY

- It is usually prescribed only for certain people

with type 2 diabetes who are felt not to be
benefit from intensive glucose control.

 The insulin regimen ranges from a single

injection to multiple injections per day using
intermediate or long acting insulin alone or with
short or rapid acting insulin or premixed
insulins.
INSULIN TREATMENT OF SPECIAL
CIRCUMSTANCES
1. Diabetic ketoacidosis:
- Life threatning medical emergency caused by
inadequate or absent insulin replacement, which
occur in patients with type 1 DM and infrequently
with type 2 DM
- S/s imclude nausea, vomiting abdominal pain deep
shallow resp (Kussmaul), change in mental status,
elevated blood and urine ketones and glucose and
arterial blood pH higher than 7.3 and low
bicarbonate.
- The fundamental treatment for DKA includes
aggressive I/V hydration and insulin therapy
and maintenance of potassium and other
electrolytes
- Regular human insulin is used for therapy
HYPEROSMOLAR HYPERGLYCEMIC
SYNDROME (HHS)
- It is diagnosed in pts with type 2 DM and is characterized
by hyperglycemia and dehydration
- Usually seen in elderly patients with inadequate oral
hydration and with presence of other illnesses and use of
other medication which causes dehydration and elevated
blood glucose level diuretics, phenytoin and steroids.
- The diagnostic hallmarks are declining mental status and
even seizures, a plasma glucose level above 600mg/dL
osmolality higher than 320mmol/L
- The treatment includes aggressive rehydration and
correction of glucose level and electrolyte
homeostatsis
- Low dose insulin therapy is required
COMPLICATIONS OF INSULIN THERAPY

A. HYPOGLYCEMIA
- Hypoglycemic reactions are the most common complicatios of
insulin therapy occur due to
 Inadequate CHO consumption
 Unusual physical exertion
 Too large dose of insulin
- Rapid development of hypoglycemia in patients with intact
hypoglycemic awareness causes signs of autonomic
hyperactivity (both sympathetic and parasympathetic) and
may progress to convulsions and coma if untreated
- On the other hand person who experiences frequent
hypoglycemic episodes the autonomic awareness is less
common or absent
- This dangerous acquired condition is termed as
“Hypoglycemic unawareness”.
- Patients don’t seek corrective measurements, as they
lack warning signs
- In patients with persistent, untreated hypoglycemia
the manifestations of insulin excess may develop
 Confusion
 Weakness
 Bizarre behaviour
 Coma and seizures
- Hypoglycemic awareness may be restored by
preventing frequent hypoglycemic episodes.
- An identification bracelet, necklace, or card should
be carried by the patients in the wallet or purse as
well as some form of rapidly absorbed glucose by
every patint receiving insulin therapy.
 TREATMENT OF HYPOGLYCEMIA

- All the manifestation of hypoglycemia are relieved by

glucose administration
 Simple sugar or glucose should be given preferably in
liquid form
 In concious patients with mild hypoglycemia who are
able to swallow, dextrose tablets, glucose gel or any
sugar containing beverage can be given.
- In more severe hypoglycemia or unconcious or
stuporous patients.. 20 – 25 ml of 50% I/V infusion
over a periods of 2-3 min. If I/V therapy is not
available than I/M or S/C injection of 1ms of glucagon
may restore conciousness.
 B. IMMUNOPATHOLOGY OF INSULIN
THERAPY

1. Insulin allergy
2. Immune insulin resistance

C. LIPODYSTROPHY AT THE SITE OF

INJECTION