Diabetes Mellitus and Insulin
By Imad Nmeir
Supervised by Doc. Lea Saab
University Holy Spirit KaslikFaculty of Science
Table of contentDiabetes Mellitus
• Definition • Type 1• Type 2• Metabolic aspect
Insulin• History • Types• Pharmacokinetics • Timing of injections• Pharmacodynamics• Adverse effectsConclusions
• Major hurdle• Solutions • Personal opinion
References
Diabetes Mellitus
Definition
Metabolic Disorder
High levels of glucose
Dysfunction and failure of various organs
Type 1 Diabetes Mellitus: T1DM
Autoimmune Disease
β cell destruction
Autoantigen specific against insulin
Type 1
Type 2 Diabetes Mellitus: T2DM
Increase in insulin resistance
Compensatory hyperinsulimenia
Chronic deficiency in glucose uptake
Rise in glucose levels
Clinical aspect of DiabetesDysfunction of insulin
Symptoms are the same
Hyperglycemia High glucose plasma levels
LipotoxicityIncrease in FFA
AutoimmunityAgainst β cellsMainly in T1DM
InflammationAutoimmunity and Islet amyloid
Islet AmyloidByproduct of β cells
Causes problem in ExcessT2DM
Insulin resistance dysfunction in insulin receptor
T2DM
IncretinsInsulin regulatory hormone
Insulin
History
Discovered in 1922Production began in 1923• Animal based
1930: chemical modification to prolong
it’s action
1978: first human recombinant insulin
produced
1982: first human recombinant utilizing
rDNA technology
1993: first results of the long term effect of insulin uptake:• Modifications to it’s
pharmacokinetics were implemented
By 1996: first short acting insulin
2005: further modifications to insulin structure were made to
improve it’s profile
History: 1993 clinical trial report
•Was done from 1983 till 1993•Long term effects of insulin•Highlighted importance of rigid daily control of glucose levels
Most important clinical trial on insulin
to date
Types:
Pharmacokinetics
It’s a protein
Subcutaneous
injections
Can’t be given in the same place
twice
Timing of injections
It is highly important that the patient be educated on the timing of insulin uptake
• Usually 30 minutes before a meal.• May change depending on the drug on-set time
pharmacodynamic
Increase plasma glucose uptake• In skeletal
muscle, liver, and adipose tissue
Metabolic effects:• Decrease
gluconeogenesis• Increase
glycogenesis
In the adipose• Increase fatty
acid production
Adverse effectsHypoglycemia
Weight gainAllergy, infection,
lipoatrophy
In case of injection in the same site more than once
Rarely: anaphylaxis
Conclusion
Major Hurdle
Several injections per day are required.
Solutions implemented:Inhaler is bulky to use
No real physiological advantage in short term use
Withdrawn from market in 2008
Inhaled insulin
Allow insulin injections to be monitored
Easier injection
Better control
Insulin pumps
Solutions implemented: Insulin pump
Personal opinion
T2DM: the correct diet and
the correct medication can cure
it
T1DM: Be hopeful, future
research holds great
promise.
References
Harper’s illustrated biochemistry; Mc Graw Hill Lange
Alternatively activated macrophages in type 1 and type 2 diabetes; Arlett Espinosa-Jimenez, Alberto N. Peon, Louis I. Terrazas.
Diabetes and beta cell functions: from mechanism to evaluation and clinical implication; Simona Cernea, Minodora Dobreanu
History of insulin; Celeste C. Quiazone, Issam Sheikh
DCCT and EDIC: the diabetic control and complications trial and follow up
Insulin-history, biochemistry, physiology and pharmacology; Shashank R. Joshi, Rakesh M. Parikh, A.K. Das
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