Professional Documents
Culture Documents
Diabetes Mellitus
Insulin
15 June 2010
THE ENDOCRINE PANCREAS
1 million islets of Langerhans
4 hormone-producing cells
Diabetes mellitus
Type 4 Type 3
Diabetes mellitus -TYPES
TYPE 1 TYPE 2
• IDDM • NIDDM
• Loss of beta • Due to insulin resistance
cells → deficiency • [or reduced insulin sensitivity]
• Combined with reduced insulin
of insulin secretion
“Juvenile diabetes” • TYPE 3
majority cases • Drug induced or other causes
• TYPE 4
in children. • Gestational diabetes mellitus
INSULIN
Proinsulin
• Exogenous:
– Liver – 40%, Kidney- 60%
In
Insulin
[-] su
l in
[-]
in
ul
Processes utilize glucose
In In
s
[Hypoglycemia]
su [+]
lin
Insulin
[+]
[+] Peripheral
utilization
Lipogenesis
Protein Synth. In Muscles
Endocrine effects of Insulin
Endocrine effects of Insulin….
Endocrine effects of Insulin….
Over view of Insulin action
Source and insulin preperations
Species A Chain B Chain
8th AA 10th AA 30th AA
Human THR ILEU THR
Pork THR ILEU ALA
Conventional prep.
Beef ALA VAL ALA •Impurities
•Antigenic
Analogs •Less expensive
1. Highly purified pork
Insulins •Replaced by
• Monocomponent insulins
1.Highly purified pork
Insulins
2.Human insulins
2. Human insulins 3.Insulin analogues
• Recombninant DNA
Technology[E.Coli, Yeast]
3. Insulin analogues
Changing or replacing AA sequences
1. Lispro
2. Aspart
3. Glulisine
4. Glargine 5. Detemir
Genetic engineering
to produce human insulin
Insulin preparations
*Long-acting insulins:
• Rapid acting insulins:
– Ultralente insulin
– Insulin lispro
Analogues
– Protamine Zinc Insulin (PZI)
– Insulin aspart
– Insulin Glargine
– Insulin glulisine Analogues
– Insulin detemir
• *Short acting insulins:
– Regular insulin
*Premixed insulins:
– 70% NPH + 30% Regular
• *Intermediate acting
– 50% NPH + 50% Regular
insulins:
– 75% NPH + 25% Lispro
– Lente insulin[Insulin Zinc
suspension *Animal or human
– NPH insulin [Isophane
Insulin suspension]
Insulin preparations
Rapid acting
• More physiologic prandial insulin replacement - their
rapid onset and early peak action - closely mimic normal
endogenous prandial insulin secretion than does regular
insulin,
• Can be taken immediately before the meal without
sacrificing glucose control.
• Their duration of action is rarely more than 4–5 hours,
which decreases the risk of late postmeal hypoglycemia.
• Lowest variability of absorption [Monomers]
• Preferred insulins for use in continuous subcutaneous
insulin infusion [CSII] devices.
Insulin preparations
Rapid acting
Lispro
Insulin preparations
Rapid acting
Aspart
Insulin preparations
Rapid acting
Glulysine
Insulin preparations
Short acting
–Onset-1-2 h
–Peak-6-12h
–Duration-18-24
–Dose related action profile
–Long acting analogs are preferred
Long actingInsulin
preparations
–Onset-1-2 h Detemir
–Peak less
–Duration-18-24
THRThriiii
• Treatment:
– Glucose administration:
• Fruit juice / Glucose gel / Sugar containing
beverage/food to eat at first sign
• If severe: 50% dextrose i.v.
Insulin Edema
• Na+ retention, Weight gain
Unitage of Insulin
• 1 U = Amount required to reduce blood glucose by
45 mg% in a fasting rabbit
• 1mg=28units
Insulin Delivery Systems
• Disposable needles and syringes: 27 G
• Portable Pen Injectors
• Jet injectors
• Continuous Subcutaneous Insulin Infusion: CSII
– Most physiologic insulin replacement
– Insulin reservoir/ Program chip/ Keypad/ Display screen
– Excellent glycemic control eg, pregnancy
• Inhaled Insulin
– Absorbed through alveolar walls
– Rapid onset of action / Short duration
– ? Pulmonary fibrosis/Pulmonary hypertension
• Oral insulin: Liposome encapsulated
Clinical Uses of Insulin
• Type 1 diabetes mellitus
• Type 2 diabetes mellitus-
Not controlled by oral agents
Complications: Diabetic ketoacidosis, Gangrene,
To tide over: Infection, Trauma
Pregnancy [Gestational diabetes not controlled by
diet alone]
• Emergency treatment of hyperkalemia: Insulin + glucose
Indications of Human Insulin
1. Insulin resistance
5. During pregnancy
Insulin regimens
• Intensive Insulin therapy-Based on formulae-
CSII
• Conventional- For type 2
• Spl circumstances
• Principle:
• Supply postprandial needs
• Provide basal control
Glargine + 3 Analogs
2Long acting+2 Rapid or Short acting
CSII
Diabetic Ketoacidocis
[Diabetic coma]
• Precipitated by Treatment:
infection, trauma,
1.Regular insulin-I.V.
stress in insulin
dependent patients 2.Bolus followed by
• Serious infusion
3.i.v fluids.
• Hypotension, shock,
tachycardia, 4.Kcl ???
dehydration, 5.NaHco3
hyperventilation, 6.Phosphate
vomiting, coma 7.Antibiotics
Drug interactions
• Beta blockers-
• Inhibit comp mechanisms
• Warning signs of hypoglycemia are masked
• Thiazides, Furosemide, Corticosteroids, OCPs,
reduce the effect of insulin
• Salicylates, Li, increase insulin secretion
Insulin Delivery Systems
Inhaled Insulin
A device that uses high
pressure
instead of a needle to propel
insulin
through the skin and into the
body.
Insulin Delivery Systems
1 - Continuous
glucose sensor
monitors blood sugar
level
2 - Data transmitted
for the computer
program to work out
‘Artificial pancreas’ insulin dose
Sensor activated pump 3 - Insulin pump
delivers the dose