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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