Ing3 Completed

THE RISK AND BENEFITS OF TEA IN GENERAL

HEALTH

Written by:

AYUNDA AFDAL

030. 09. 040

FACULTY OF MEDICINE

TRISAKTI UNIVERSITY

JAKARTA, DECEMBER 2012

ABSTRACT

All tea is produced from a plant called Camellia sinensis.1 The Camellia

Sinensis plant is native to Asia, but is currently cultivated around the world in

tropical and subtropical areas. With over 3,000 varieties, tea is the most

consumed beverage in the world after water.2 Tea can be divided into five basic

categories: black, green, oolong, white, and puerh.

Tea contains a large number of potentially bioactive chemicals, including

flavonoids (antioxidant), polyphenols, vitamins & mineral, theanine, caffeine,

and several polysaccharides, and a variety of health effects have been proposed

and investigated. Due to modern day environmental pollution fluoride and

aluminium have also been found to occur in tea. Tea also contains small

amounts of theobromine and theophylline. 3

Keywords : tea, antioxidant, flavinoids, polyphenols, vitamin & mineral,

theanine, caffeine.

http://en.wikipedia.org/wiki/Flavinoid

http://en.wikipedia.org/wiki/Theophylline

http://en.wikipedia.org/wiki/Theobromine

http://en.wikipedia.org/wiki/Aluminium

http://en.wikipedia.org/wiki/Fluoride

http://en.wikipedia.org/wiki/Polysaccharide

http://en.wikipedia.org/wiki/Caffeine

http://en.wikipedia.org/wiki/Vitamin

INTRODUCTION

People have turned to tea to soothe body and soul for more than 5,000

years. In China, tea has served medicinal purposes since ancient times.

According to the November issue of Mayo Clinic Women's HealthSource,

modern science has confirmed potential health benefits of tea. 4

Tea is an aromatic beverage commonly prepared by pouring hot or

boiling water over cured leaves of the tea plant. All tea is produced from a plant

called Camellia sinensis.1 The Camellia Sinensis plant is native to Asia, but is

currently cultivated around the world in tropical and subtropical areas. With

over 3,000 varieties, tea is the most consumed beverage in the world after water.

The differences between teas arise from processing, growing conditions,

and geography. The fermentation process of these leaves also defines the

different types of teas. Black tea undergo long fermentation. Green and white

tea undergo the least processing and are steamed quickly. All teas contain

polyphenols. Tea can be divided into five basic categories: black, green, oolong,

white, and puerh.

Black tea is allowed to wither, which precedes a process called oxidation

(sometimes incorrectly referred to as fermentation) during which water

evaporates out of the leaf and the leaf absorbs more oxygen from the air. Black

teas usually undergo full oxidation, and the results are the characteristic dark

brown and black leaf, the typically more robust and pronounced flavors of black

teas, and, when brewed appropriately, a higher caffeine content compared to

other teas (50-65% of coffee, depending on the type and brewing technique).

Green tea is allowed to wither only slightly after being picked. Then the

oxidation process is stopped very quickly by firing (rapidly heating) the leaves.

Therefore, when brewed at lower temperatures and for less time, green teas tend

http://en.wikipedia.org/wiki/Beverage

to have less caffeine (10-30% of coffee).

Oolong tea (also known as wulong tea) is allowed to undergo partial

oxidation. These teas have a caffeine content between that of green teas and

black teas. The flavor of oolong (wulong) teas is typically not as robust as

blacks or as subtle as greens, but has its own extremely fragrant and intriguing

tones. Oolongs (wulongs) are often compared to the taste and aroma of fresh

flowers or fresh fruit.

White teas are the most delicate of all teas. They are appreciated for their

subtlety, complexity, and natural sweetness. They are hand processed using the

youngest shoots of the tea plant, with no oxidation. When brewed correctly,

with a very low temperature and a short steeping time, white teas can produce

low amounts of caffeine.

Puerh is an aged black tea from China prized for its medicinal properties

and earthy flavor. It is perhaps the most mysterious of all tea. Until 1995 it was

illegal to import it into the U.S., and the process of its production is a closely

guarded state secret in China. It is very strong with an incredibly deep and rich

flavor, and no bitterness, and an element that could best be described as almost

peaty in flavor. 2







It has been suggested that green and black tea may protect against cancer,

though the catechins found in green tea are thought to be more effective in

http://en.wikipedia.org/wiki/Catechin









preventing certain obesity-related cancers such as liver and colorectal while

both green and black tea may protect against cardiovascular disease. 3

Numerous recent epidemiological studies have been conducted to

investigate the effects of green tea consumption on the incidence of human

cancers. These studies suggest significant protective effects of green tea against

oral, pharyngeal, esophageal, prostate, digestive, urinary tract, pancreatic,

bladder, skin, lung, colon, breast, and liver cancers, and lower risk for cancer

metastasis and recurrence.6

Healthy consumption of two to three cups a day may reduce the chances

of heart attack and stroke. Drinking tea may keep the arteries smooth and clog-

free. Dr. Carrie Ruxton and colleagues at Kings College London found clear

evidence that drinking three to four cups of tea a day can cut the chances of

having a heart attack.3

http://en.wikipedia.org/wiki/Cardiovascular_disease

http://en.wikipedia.org/wiki/Colorectal_cancer

http://en.wikipedia.org/wiki/Liver_cancer

http://en.wikipedia.org/wiki/Cancer

http://en.wikipedia.org/wiki/Obesity

DISCUSSION







Antioxidants counter the harmful effects of free radicals. Free radicals are

unstable molecules that attack other molecules in the body, leading to cell

damage. Antioxidants inhibit the oxidation reactions caused by free radicals,

thereby preventing damage to cells and tissues. The type and amount of

flavonoid contained in tea depends on the variety of leaf, growing environment,

processing, and brewing method. Green tea contains mostly simple flavonoids

called catechins while black tea contains more complex varieties called

theaflavins and thearubigins. Re3Scientists have demonstrated that flavonoids,

which are polyphenolic compounds, exhibit antioxidant activity. 14

Catechin is a flavan-3-ol, a type of natural phenol and antioxidant. It is a

plant secondary metabolite. It belongs to the group of flavan-3-ols (or simply

flavanols). It is often considered to belong to the family of flavonoids.

Catechins are highest in concentration in white and green teas, while black tea

has substantially fewer due to its oxidative preparation. The health benefits of

catechins have been studied extensively in humans and animal models. Many

studies on health benefits have been linked to the catechin content. According to

Norman Hollenberg, professor of medicine at Harvard Medical School,

epicatechin can reduce the risk of four of the major health problems: stroke,

heart failure, cancer and diabetes.

Polyphenol protect cells and body chemicals against damage caused by

free radicals, reactive atoms that contribute to tissue damage in the body.

http://www.weight-loss-diet-tips-4-life.com/free-radicals.html

http://en.wikipedia.org/wiki/Epicatechin

http://en.wikipedia.org/wiki/Harvard_Medical_School

http://en.wikipedia.org/wiki/Health_benefits_of_tea

http://en.wikipedia.org/wiki/Flavonoids

http://en.wikipedia.org/wiki/Flavan-3-ol

http://en.wikipedia.org/wiki/Secondary_metabolite

http://en.wikipedia.org/wiki/Plant

http://en.wikipedia.org/wiki/Antioxidant

http://en.wikipedia.org/wiki/Flavan-3-ol

http://theteaspot.com/loose-leaf-tea-black-tea/

http://theteaspot.com/loose-leaf-tea-green-tea/









Polyphenols is a kind of chemical that may protect against some common health

problems and possibly certain effects of aging. They can also block the action

of enzymes that cancers need for growth and they can deactivate substances that

promote the growth of cancers.

In addition, polyphenols also activate the key enzyme (AMP kinase) that

helps restore cellular ATP levels. At high enough levels, these chemical

substances can exert an anti-inflammatory effect by inhibiting the activation of

inducible inflammatory proteins that normally occurs once the innate immune

system has been activated. Blood levels of polyphenols will peak soon after

they are consumed, then decrease as they are metabolized or excreted from the

body. Some will not be absorbed into the bloodstream, but will merely pass

through the digestive tract. These are very important as well because they may

help to prevent colon cancer and such diseases.

Polyphenols actively work in the body to prevent certain disease

mechanisms from occuring. They work in the body to enhance health in

complex ways, and as such they are not simply antioxidants. Their specific

health-promoting actions are still being actively researched, and it is generally

recognized that polyphenols can reduce the risk factors for cardiovascular

disease and basically help to protect many body systems from the risks or

ravages of many types of chronic disease.

The following vitamins are naturally found in tea:

• Vitamin C – a recent study showed that black tea, green tea and oolong tea are

all extremely good sources of vitamin C, a potent antioxidant.

• Carotene, a precursor to vitamin A, has antioxidant and protective properties.

• Thiamine (vitamin B1) and pantothenic acid are necessary for the release of

http://theteaspot.com/loose-leaf-tea-oolong-tea/

http://theteaspot.com/loose-leaf-tea-green-tea/

http://theteaspot.com/loose-leaf-tea-black-tea/

http://www.weight-loss-diet-tips-4-life.com/digestive-system.html

http://www.weight-loss-diet-tips-4-life.com/anti-inflammatory.html

energy from fat and carbohydrate. (pictured here)

• Vitamin B6 is involved in metabolism proteins

• Folic Acid plays a role in cell division.

Tea is a good source of essential minerals:

• Manganese is essential for bone growth and development.

• Potassium is vital for maintaining a healthy heart. It enables nerves and

muscles to function and regulates fluid levels within the cells. Deficiency

leads to erratic heartbeat and fatigue.

• Fluoride is the most successful agent against.tooth decay ever discovered. Tea

is one of the few natural sources of fluoride. High fluoride intake (daily

intakes over 2 mg for children, 4 mg adults) increases the risk

osteofluorosis and fractures.12

Theanine is an amino acid found in tea. Theanine has a chemical structure

very similar to glutamate, a naturally occurring amino acid in the body that

helps transmit nerve impulses in the brain. Theanine has been shown to reduce

mental and physical stress. Theanine also promotes alpha wave production in

the brain, which is the part of the brain that is stimulated during meditation.

Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a

stimulant drug. In humans, caffeine acts as a central nervous system stimulant,

temporarily warding off drowsiness and restoring alertness, alleviating fatigue,

increasing wakefulness, and improving concentration and focus. Caffeine is

toxic at sufficiently high doses. Ordinary consumption can have low health

risks, even when carried on for years – there may be a modest protective effect

against some diseases, including certain types of cancer. Caffeine can have both

positive and negative effects on anxiety disorders. Some people experience

http://en.wikipedia.org/wiki/Cancer

http://en.wikipedia.org/wiki/Central_nervous_system

http://en.wikipedia.org/wiki/Stimulant

http://en.wikipedia.org/wiki/Alkaloid

http://en.wikipedia.org/wiki/Xanthine

http://en.wikipedia.org/wiki/Crystalline

http://www.webmd.com/brain/picture-of-the-brain

sleep disruption if they consume caffeine, especially during the evening hours,

but others show little disturbance and the effect of caffeine on sleep is highly

variable. 5.8

Effect on the body :

• Hormones- You can feel the effects of caffeine in your system within a few

minutes of ingesting it, and it stays on your system for many hours—it

has a half-life of four to six hours in your body. While in your body,

caffeine affects the following hormones:

• Adenosine- Can inhibit absorption of adenosine, which calms the body, which

can make you feel alert in the short run, but can cause sleep problems

later.

• Adrenaline- Caffeine injects adrenaline into your system, giving you a

temporary boost, but possibly making you fatigued and depressed later. If

you take more caffeine to counteract these effects, you end up spending

the day in an agitated state, and might find yourself jumpy and edgy by

night.

• Cortisol- Can increase the body’s levels of cortisol, the “stress hormone”,

which can lead to other health consequences ranging from weight gain

and moodiness to heart disease and diabetes.

• Dopamine- Caffeine increases dopamine levels in your system, acting in a

way similar to amphetamines, which can make you feel good after taking

it, but after it wears off you can feel ‘low’. It can also lead to a physical

dependence because of dopamine manipulation.

These changes caffeine makes in your physiology can have both positive

and negative consequences:

• Sleep.

Caffeine can affect your sleep by keeping you awake longer, thereby

http://stress.about.com/od/lowstresslifestyle/a/powernap.htm

http://stress.about.com/od/stresshealth/a/cortisol.htm

http://stress.about.com/od/stressmanagementglossary/g/Adrenalin.htm

http://stress.about.com/od/lowstresslifestyle/a/powernap.htm

http://en.wikipedia.org/wiki/Insomnia

shortening the amount of sleep you get, and giving you less time in the

restorative stages of sleep, which takes a toll on your level of alertness the

next day and overall health. Interestingly, though, caffeine doesn’t affect

the stages of sleep the way other stimulants do, so it’s a better choice than

speed or other ‘uppers’ to use if you need to stay awake.

• Weight.

Many experts believe that increased levels of cortisol lead to stronger

cravings for fat and carbohydrates, and cause the body to store fat in the

abdomen. (Abdominal fat carries with it greater health risks than other

types of fat.) Also, if increased cortisol levels lead to stronger cravings

for caffeine-laden foods, the body goes into a cycle that leads only to

worse health. The good news, though, is that caffeine can speed up

metabolism. Also, it can help the body break down fat about 30% more

efficiently if consumed prior to exercise. (You must be exercising to get

this benefit, though.) Additionally, caffeine can keep blood sugar levels

elevated, leaving you feeling less hungry.

• Exercise.

If caffeine elevates levels of cortisol and other hormones for a temporary

boost, after caffeine wears off, the body can feel fatigued and feelings of

mild to moderate depression can set in. This can make physical activity

more difficult. On the positive side, caffeine has been found to enhance

physical performance and endurance if it isn’t overused. This, combined

with its effect of fat burning during exercise, can actually enhance

workouts and enable you to get in better shape if you take it at the right

time.8

How the tea is actually prepared plays an important role in how much

caffeine makes it into your cup. Everything, from the amount of tea used to

water temperature and brewing time to whether the leaves are steeped loose, in

a tea bag, or strainer, becomes a factor. In general, though, more tea, hotter

water, and longer steeping all contribute to more caffeine pecup.

A report by the Department of Nutritional Services provides the

following ranges of caffeine content for a cup of tea made with loose leaves: 9

Beverage Caffeine

White Tea 6-25 mg

Green Tea 8-36 mg

Oolong Tea 12-55 mg

Black Tea 23-110 mg

For most healthy adults, moderate doses of caffeine — 200 to 300

milligrams (mg), or about two to four cups of brewed coffee a day — aren't

harmful. But some circumstances may warrant limiting or even ending your

caffeine routine.

Although moderate caffeine intake isn't likely to cause harm, too much

can lead to some unpleasant effects. Heavy daily caffeine use — more than 500

to 600 mg a day — may cause: insomnia, nervousness, restlessness, irritability,

stomach upset, fast heartbeat, muscle tremors. 7

Drinking tea is actually better for you than drinking water. Water is

essentially replacing fluid. Tea replaces fluids and contains antioxidants, so it's

got two things going for it." Tea keeps people hydrated. A caffeinated beverage,

tea definitely contributes to the fluid needs, except when taken in a high

quantity (more than five or six cups at one time). Drinking tea may develop a

strong immune system and prevent the body against infection. Claire

Williamson of the British Nutrition Foundation said, "Studies in the laboratory

have shown potential health benefits.” 11

http://www.suite101.com/functions/article/edit.cfm/239264

Drinking tea leads to certain health hazards which can't be ignored.

Researchers show that anemic people should avoid drinking tea around meal

times as it can impair the body's ability to absorb iron from food. If tea is

consumed with sugar, it my lead to health ill effects like acidity, tooth decay

and gum problems. More than three to four cups of tea a day is not considered

healthy for the body.

Drinking three to four cups of tea without any sugar and cream is a

healthy choice, offering many health benefits. The beneficial polyphenols are

derived to the maximum if tea is brewed for at least three to five minutes. The

aromatic flavor rejuvinates the mind and keeps the body fit and healthy. 6

CONCLUSION




and investigated.3 Drinking three to four cups of tea is a healthy choice, offering

many health benefits. But more than three to four cups of tea a day is not

considered healthy for the body. 11





REFERENCES

1. Laura C. Martin (15 May 2007). Tea: The Drink that Changed the World.

Tuttle Publishing. p. 8. Retrieved 31 October 2012.

2. Edgar Julie. Types of Tea and Their Health Benefits. Available at:

http://www.webmd.com/diet/features/tea-types-and-their-health-benefits.

Accessed on : December 3rd 2012.

3. Brown CA, Bolton‐Smith C, Woodward M, Tunstall‐Pedoe H. Coffee

and tea consumption and the prevalence of coronary heart disease in men

and women: results from the Scottish Heart Health Survey. J Epidemiol

Com Health1993; 47:171–5.

4. Mayo Clinic Staff. Tea : Enjoy a Cup for Health and Pleasure. Available

at : http://www.mayoclinic.org/news2010-mchi/6046.html. Accessed on :

December 3rd 2012.

5. Bell Kimberly. Theanine. Available at :

http://www.webmd.com/vitamins-supplements/ingredientmono-

1053THEANINE.aspx?. Accessed on : December 3rd 2012.

6. Benefit of drinking green tea. Available at :

http://www.health.harvard.edu/press_releases/benefit_of_drinking_green

_t. Accessed on : December 3rd 2012.

7. Magee Elaine. Healthier Ways to Get Your Caffeine. Available at :

http://www.webmd.com/diet/features/healthier-ways-to-get-your-

caffeine. Accessed on : December 3rd 2012.

8. Attwood A, et al. Differential responsiveness to caffeine and perceived

effects of caffeine in moderate and high regular caffeine consumers.

Psychopharmacology. 2007;190:469.

9. Caffeine. Natural Medicines Comprehensive Database. Available on :

http://www.naturaldatabase.com. Accessed December 9th 2012.

http://www.webmd.com/diet/features/healthier-ways-to-get-your-caffeine

http://www.webmd.com/diet/features/healthier-ways-to-get-your-caffeine

http://www.health.harvard.edu/press_releases/benefit_of_drinking_green_t

http://www.health.harvard.edu/press_releases/benefit_of_drinking_green_t

http://www.webmd.com/vitamins-supplements/ingredientmono-1053THEANINE.aspx

http://www.webmd.com/vitamins-supplements/ingredientmono-1053THEANINE.aspx

http://www.mayoclinic.org/news2010-mchi/6046.html

http://www.webmd.com/diet/features/tea-types-and-their-health-benefits

http://books.google.co.uk/books?id=DJ2j_bX6WTUC&pg=PA8#v=onepage&q&f=false

10.Chin JM, et al. Caffeine content of brewed teas. Journal of Analytical

Toxicology. 2008;32:702.

11.Mayo clinic staff. Caffeine : How much is too much?. Available on :

http://www.mayoclinic.com/health/caffeine/AN01211 . Accessed on :

December 3rd 2012.

12. Jianyun Ruan and Ming H. Wong. "Accumulation of Fluoride and

Aluminium Related to Different Varieties of Tea Plant". Environmental

Geochemistry and Health. 2001. p.53–63.

13. Spencer, Jeremy P. E. "Flavonoids: modulators of brain function?".

British Journal of Nutrition. 2009. p.60–77.

14. Mattill, H A. "Antioxidants". Annual Review of Biochemistry. 2009. p.

77–92.

http://www.mayoclinic.com/health/caffeine/AN01211

ISO Implementation in Medical Practice

Azmi Ikhsan Azhary

030.09.043

FACULTY OF MADICINE

TRISAKTI UNIVERSITY

2012

Abstract

ISO, stands for International Standardization Organization is an international standard-setting

body composed of representatives from various national standards organizations. ISO sets the

standards of many things. ISO ensure that products and services are safe, reliable and of good

quality. In medical field, they sets standards in some areas, but I will only talk about 1

standard that I think is very crucial. ISO 15189 about Medical laboratories — Particular

requirements for quality and competence.

ISO 15189is for use by medical laboratories in developing their quality management systems

and assessing their own competence, and for use by accreditation bodies in confirming or

recognising the competence of medical laboratories.1

Keywords: ISO, Quality Management System, ISO 15189

http://en.wikipedia.org/wiki/Standards_organizations

http://en.wikipedia.org/wiki/International_standard

Introduction

About ISO

The International Organization for Standardization (ISO) is a worldwide federation of national

standards bodies from some 100 countries.ISO is a non-governmental organization established in

1947. The mission of ISO is to promote the development of standardization and related activities in

the world with a view to facilitating the international exchange of goods and services, and to

developing cooperation in the spheres of intellectual, scientific, technological and economic

activity.ISO's work results in international agreements are published as International Standards.2

International standardization : What does it achieve ?

Industry-wide standardization is a condition existing within a particular industrial sector when the

large majority of products or services conform to the same standards. It results from consensus

agreements reached between all economic players in that industrial sector - suppliers, users, and

often governments. They agree on specifications and criteria to be applied consistently in the choice

and classification of materials, the manufacture of products, and the provision of services. The aim is

to facilitate trade, exchange and technology transfer through :

Enhanced product quality and reliability at a reasonable price,

Improved health, safety and environmental protection, and reduction of waste,

Greater compatibility and interoperability of goods and services,

Simplification for improved usability,

Reduction in the number of models, and thus reduction in costs,

Increased distribution efficiency, and ease of maintenance.

Users have more confidence in products and services that conform to International Standards.

Assurance of conformity can be provided by manufacturers' declarations, or by audits carried out by

independent bodies.3

The ISO Standardization Process

Each member body who has an interest in the work of a committee is entitled to be a member of

that committee. Standards are reached by consensus with each member organization representing

the interests of the vendors, manufacturers, consumers, profession als, and government of it's

country.

Each standard goes through a six stage process before being published as an ISO standard.

The first stage is the proposal stage in which a need for a standard is determined and

members are identified who are willing to work on it. The standards then ent ers the

preparatory stage where a working draft of the standard is developed. When the working draft

is completed, it enters the committee stage and is sent out for comments until a consensus is

reached. The output of this stage is the Draft Internation al Standard (DIS). The DIS then

enters the enquiry stage where it is circulated among all member bodies and then voted upon.

If a DIS does not receive 75% of the vote, it returns to lower stages and work on it continues.

If it passes the enquiry stage , it becomes a Final Draft International Standard and enters the

approval stage. During this stage it will again circulate through all member bodies for a final

vote and again it must pass this stage with 75% of the vote. If the standard passes this stage, it

enters the publication stage and is sent to the ISO Central Secretariat for publication.4

ISO 15189

ISO 15189 (Medical laboratories - particular requirements for quality and competence) is a standard

which contains requirements for medical laboratories to prove their competence in providing

trustworthy service. This standard contains the competence of personnel that involved in the

examination in the medical laboratory, the facility and its equipment, reagents and supplies, factors

pre-inspection, inspection, quality assurance considerations, and factors of post-inspection.

It is an initiative that presents a global concerted approach in creating a standardized measure for

management practices in medical laboratories. An ISO 15189 certification has been seen as a critical

initiative towards harmonizing global practices in medical laboratories towards a common measure

of quality assurance and safety. The approach takes into account a lot of perspectives, including the

interpretation of test results, the method patient samples are actually collected as well as the time

required for the tests to be carried out.

The following are the basic requirements for ISO 15189 certification:

A well documented procedure analysis by the laboratories.

Training manual provided by the laboratories.

ISO 15189 requires an effective detailed analysis of medical laboratory procedures in a bid to

make sure that all weaknesses have been identified.

Detailed evaluation reports of the existing quality management system as well as other

monitoring and evaluation reports.

A detail audit of management reviews5

Discussions

According to my source, The ISO 15189 certification has a set of benefits.

The benefits are listed here below:

An ISO 15189 certification promotes development of an international reputable image for

your organization through Quality Assurance and Management Systems.

Promotes a strong degree of consistency in compliance to medical laboratory laws and

legislation both from an international and national perspective.

Fundamentally critical in promoting laboratory efficiency and responsibility for better results

and service delivery.

The certification program also has been very critical in promoting modern laboratory

practices that include professionalism and expertise in conduction of medical activities in the

labs.

Ultimately promoted the growth of customer satisfaction.6

I think ISO 15189 must be implemented to all of medical laboratory, but in some developing

countries, the implementation is still not adequately do. Example, in Indonesia there is some kind of

accreditation committee, called Komite Akreditasi Nasional (KAN) formed in 1992. Until July 2012,

KAN has accredited 21 private medical laboratories, three government health laboratories and one

government hospital laboratories. The scope of accreditation of medical laboratories that have been

accredited were include clinical chemistry, urinalysis, microbiology, immunology, hematology,

hemostasis, Drug, and anatomical pathology. For the scope of anatomic pathology laboratory, one

particular clinical pathologist was accredited. To do the medical laboratory accreditation, KAN is use

the ISO 15189 as a standard.

The number of laboratory that has been accredited is very small (according to KAN’s data, until July

2012, only about 25 laboratories that accredited). Because in Indonesia, there are so many medical

laboratories. This data indicated that the implementation of ISO 15189 in Indonesia was not done

well. 7

Conclusion

ISO 15189 is a global initiative that aims at creating a standard measure of quality in medical

laboratories. The standard has developed initiatives to promote competence and responsibility in

medical laboratory processes, equipments and outcomes. ISO 15189 was developed by the

International Standards Organizations Technical Committee and has been implemented in over 200

countries. The process involves testing of the effectiveness of laboratory equipments and the impact

those particular equipment have on the processes in the labs and their outcomes.

ISO 15189 must be implemented in any of medical laboratory, because it can promotes development

of laboratory efficiency and responsibility for better result. In the other hand, the efficiency and

better result from the lab can ultimately promoted the growth of customer satisfaction.

I think the solution to implement the ISO 15189 to other lab, is the government should point some

big lab (that has been accreditated) as a temporary model for them, until they qualified to be

accredited by KAN.

References

1. International Standardization Organization. ISO 15189:2007. Available at

http://www.iso.org/iso/catalogue_detail?csnumber=42641 Accessed December 8th

2012.

2. International Standardization Organization. About ISO. Available at

http://www.iso.org/iso/home/about.htm Accessed December 8th 2012.

3. University of Wisconsin-Madison. Introduction to ISO. Available at

http://trace.wisc.edu/docs/taacmtg_sep96/iso.htm Accessed December 8th 2012.

4. University of Pittsburgh. School of Information Sciences: The ISO Standardization

Process. Available at:

http://www.sis.pitt.edu/~mbsclass/standards/martincic/isohistr.htm Accessed

December 8th 2012.

http://www.sis.pitt.edu/~mbsclass/standards/martincic/isohistr.htm%20Accessed%20December%208th%202012

http://www.sis.pitt.edu/~mbsclass/standards/martincic/isohistr.htm%20Accessed%20December%208th%202012

http://trace.wisc.edu/docs/taacmtg_sep96/iso.htm

http://www.iso.org/iso/home/about.htm%20Accessed%20December%208th%202012

http://www.iso.org/iso/catalogue_detail?csnumber=42641

5. Quality Systems Enhancement. ISO 15189 – Quality Management in Medical

Laboratories. Available athttp://www.enhancequality.com/iso-standards/iso-

15189-medical-laboratories-particular-requirements-for-quality-and-

competence/ Accessed December 8th 2012.

6. Quality Systems Enhancement. ISO 15189 – Quality Management in Medical Laboratories.

Available at http://www.enhancequality.com/iso-standards/iso-15189-medical-laboratories-

particular-requirements-for-quality-and-competence/ Accessed December 8th 2012.

7. Komite Akreditasi Nasional. Akreditasi Laboratorium Medik Berdasarkan SNI ISO

15189:2009. Available at http://www.kan.or.id/?p=2214&lang=id Accessed December 8th

2012.

http://www.kan.or.id/?p=2214&lang=id

http://www.enhancequality.com/iso-standards/iso-15189-medical-laboratories-particular-requirements-for-quality-and-competence/



THE AWARENESS OF OCCUPATIONAL HEALTH IN INDONESIA

BATHIN BONIA SARI

030.09.044

JAKARTA 2012

ABSTRACT

Occupational Health is the promotion and maintenance of the highest degree of physical,

mental and social well-being of workers in all occupations by preventing departures from

health, controlling risks and the adaptation of work to people, and people to their jobs.

(ILO / WHO 1950)

The health of the workers has several determinants, including risk factors at the workplace

leading to cancers, accidents, musculoskeletal diseases, respiratory diseases, hearing loss,

circulatory diseases, stress related disorders and communicable diseases and others.

What we are going to discuss are the relation of Noise-Induced, hearing loss, treatment, and

prevention that can be done.

Because there are numerous workers that experiences hearing loss after exposed to noise or

high frequency sounds from work and environment.

Keyword : occupational health, noise induce, hearing loss

CHAPTER I

INTRODUCTION

During the 1990s, Indonesia, as many other Asian countries, has undergone a period

of rapid growth until 1997 and suffered subsequently from the financial crisis. Both phases

have their own peculiarities: during the growth, the number of work-related injuries tends to

increase, whereas during the recession, unfortunately, occupational safety and health (OSH)

becomes one of the first areas to be curtailed. The ILO views that workers’ safety and health

is a basic human right and this right has to be secured no matter whether the country is in

economic growth or in recession. We should not be too preoccupied to make or save money

at the expense of human lives and health.(1)

Work is something that can not be separated from human life, especially people who are in

the productive age (20-50th). There are many risks in their work both in terms of health and

safety. Companies and workers should pay attention to it

Occupations that increases the chance of noise-induced hearing loss are agriculture,

construction, manufacture utility, transportation, and military.(2)

In each state has regulations governing occupational health and safety, including in

Indonesia.

Indonesia has a legal framework Safety Act (Act No.1, 1970). This law covers all workplaces

and emphasize primary prevention.(3)

Undang-undang Kesehatan (UU No 23, 1992) dedicates its Article 23 for occupational health

stated that all workers to work in good health without endangering themselves or their

communities, and to obtain an optimal work productivity

along with labor protection program (Departemen Kesehatan, 2002)

(Pasal 86 dan 87). The law stipulates that every worker is entitled to receive the protection of

safety and health hazards, protection against immorality and indecency, and treatment that

shows respect for human dignity and religious values. Second, states that every company

must implement OSH-MS

Based on the Employees’ Social Security Act in 1992 (UU No.3, 1992), the

Government established a public limited liability company, PT JAMSOSTEK.18 The Act

covers the benefits related to (i) employment accidents, (ii) old age, (iii) death, and (iv) health

care. The compulsory coverage applies to employers hiring 10 employees or more, or paying

a monthly wage payroll of 1 million Rupiahs or more. Workers injured at work are entitled to

benefits covering (i) the cost of transportation, (ii) the cost of medical examination, treatment,

and/or hospital care, (iii) the cost of rehabilitation, and (iv) cash payments consisting

disability or death allowances.(4)

But unfortunately the workers and firms in Indonesia are not too aware on health at work and

their safety in doing their jobs. As conveyed by KSPSI (Confederation of All Indonesian

Workers Union) that the workers have very low awareness of OSH, compared with issues

such as wages.

" People tend to think that they should get paid enough, to meet the needs of their incomes,

and improve the well-being before they are "able to" think OSH”

CHAPER II

LITERATURE REVIEW

I. Occupational health




(ILO / WHO 1950)

Occupational health problems occur at work or because of the kind of work you do. These

problems can include

Cuts, broken bones, sprains and strains, or amputations Repetitive motion disorders

Hearing problems caused by exposure to noise

Vision problems or even blindness

Illness caused by breathing, touching or ingesting unsafe substances

Illness caused by exposure to radiation

Exposure to germs in healthcare settings

NIOSH surveyed around 30 million workers affected hearing loss from loud noises and high

frequency sounds and 9 million people from solvent and metal.(5)

44% carpenter and 48% plumbers reported that they realized to have noise-induced hearing

loss and affects real life.

http://www.nlm.nih.gov/medlineplus/occupationalhealthforhealthcareproviders.html

http://www.nlm.nih.gov/medlineplus/radiationexposure.html

http://www.nlm.nih.gov/medlineplus/noise.html

49% miners will have noise-induced hearing loss at the age of 50 which is 9% to 70% at the

age of 60.

2. Noise induce hearing loss

Noise induced hearing loss is a permanent hearing impairment resulting from prolonged exposure to

high levels of noise. One in 10 man has a hearing loss that affects his or her ability to understand

normal speech. Excessive noise exposure is the most common cause of hearing loss. The National

Institute of Health reports that about 15 percent of aged 20 to 69 have high frequency hearing loss

related to occupational or leisure activities. Because of occupational risk of noise induced hearing

loss, there are government standards regulating allowable noise exposure. People working before

the mid1960s may have been exposed to higher levels of noise where there were no laws mandating

use of devices to protect hearing. (6)

CAPTER III

DISCUSION

Occupational health




(ILO / WHO 1950)

The health of the workers has several determinants, including risk factors at the workplace

leading to cancers, accidents, musculoskeletal diseases, respiratory diseases, hearing loss,

circulatory diseases, stress related disorders and communicable diseases and others.(7)

How we hear

Hair cells in the inner ear

Hearing depends on a series of events that change sound waves in the air into electrical

signals. Our auditory nerve then carries these signals to the brain through a complex series of

steps.

Sound waves enter the outer ear and travel through a narrow passageway called the ear canal,

which leads to the eardrum.

The eardrum vibrates from the incoming sound waves and sends these vibrations to three tiny

bones in the middle ear. These bones are called the malleus, incus, and stapes.

The bones in the middle ear amplify, or increase, the sound vibrations and send them to the

inner ear—also called the cochlea—which is shaped like a snail and is filled with fluid. An

elastic membrane runs from the beginning to the end of the cochlea, splitting it into an upper

and lower part. This membrane is called the “basilar” membrane because it serves as the

base, or ground floor, on which key hearing structures sit.

The sound vibrations cause the fluid inside the cochlea to ripple, and a traveling wave forms

along the basilar membrane. Hair cells—sensory cells sitting on top of the membrane—“ride

the wave.”

As the hair cells move up and down, their bristly structures bump up against an overlying

membrane and tilt to one side. This tilting action causes pore-like channels, which are on the

surface of the bristles, to open up. When that happens, certain chemicals rush in, creating an

electrical signal.

The auditory nerve carries this electrical signal to the brain, which translates it into a “sound”

that we recognize and understand.

Hair cells near the base of the cochlea detect higher-pitched sounds, such as a cell phone

ringing. Those nearer the apex, or centermost point, detect lower-pitched sounds, such as a

large dog barking.

Hearing loss

Exposure to harmful sounds causes damage to the hair cells as well as the auditory, or

hearing, nerve (see figure). Impulse sound can result in immediate hearing loss that may be

permanent. This kind of hearing loss may be accompanied by tinnitus—a ringing, buzzing, or

roaring in the ears or head—which may subside over time. Hearing loss and tinnitus may be

experienced in one or both ears, and tinnitus may continue constantly or occasionally

throughout a lifetime.(6)

Continuous exposure to loud noise also can damage the structure of hair cells, resulting in

hearing loss and tinnitus, although the process occurs more gradually than for impulse noise.

Exposure to impulse and continuous noise may cause only a temporary hearing loss. If a

person regains hearing, the temporary hearing loss is called a temporary threshold shift. The

temporary threshold shift largely disappears 16 to 48 hours after exposure to loud noise. You

can prevent NIHL from both impulse and continuous noise by regularly using hearing

protectors such as earplugs or earmuffs.

When a person is exposed to loud noise over a long period of time, symptoms of NIHL will increase

gradually. Over time, the sounds a person hears may become distorted or muffled, and it may be

difficult for the person to understand speech. Someone with NIHL may not even be aware of the

loss, but it can be detected with a hearing test.

ONIHL is a more common cause of noise-induced hearing loss (NIHL) for the following 2 reasons: (1)

The threat of loss of employment may convince people to remain in environments with noise levels

higher than they would otherwise accept, and (2) in the workplace, high levels of noise may be

sustained on a regular basis for many hours each day over many years

ONIHL is 100 percent preventable. All individuals should understand the hazards of noise

and how to practice good hearing health in everyday life. To protect your hearing: (8)

Know which noises can cause damage (those at or above 85 decibels).

Wear earplugs or other hearing protective devices when involved in a loud activity

(special earplugs and earmuffs are available at hardware and sporting goods stores).

Be alert to hazardous noise in the environment.

Protect the ears of children who are too young to protect their own.

Make family, friends, and colleagues aware of the hazards of noise.

If you suspect hearing loss, have a medical examination by an otolaryngologist (a

physician who specializes in diseases of the ears, nose, throat, head, and neck) and a

hearing test by an audiologist (a health professional trained to measure and help

individuals deal with hearing loss).

Workers’ low OSH awareness is an indisputable concern. Nevertheless, it is

necessary to emphasize that the lack of understanding is not a case of workers alone: work

safety and health awareness is low among all. Medical doctors receive insufficient OSH

training; this results in difficulties in diagnosing illnesses and linking them to workplace

hazard exposures, thus, hindering the primary prevention at the workplace.

Besides medical doctors, mainstream engineers are frequent key players in safety and health.

Usually, these conventional engineers do not receive adequate OSH education either; for

example, only few chemical and mechanical engineers are required to demonstrate their

comprehension in toxics use reduction, safer and cleaner product design, or on industrial

hygiene. Nevertheless, “engineering controls” are on the top of the hazard control hierarchy

to eliminate and minimize work safety and health risks.

More often than not, most business school graduates have studied hardly any work safety and

health subjects. Any entrepreneur who considers

starting a business needs at least basic knowledge and skills in the workplace risk

identification, exposure assessment, existing OSH regulatory requirements, etc to implement

preventive measures against accident and health hazards successfully.

Furthermore, when one describes working conditions in developing and even in

developed countries, the first, the most frequently-heard, and unfortunately often the only

narrative is: “workers do not use respirators or masks”. Sadly, these workers-don’t-use-masks

attitudes indicate how poorly hazard prevention principles have been instilled in societies. It

is not that only workers’ OSH awareness is low – the global OSH awareness is low.

NIOSH recommends that all workers' exposure to noise must be controlled under a level

equivalent to 85 dBA for eight hours of work to minimize noise-induced hearing loss.

NIOSH also recommends 3 dBA exchange rate so that each increase of 3 dBA doubles the

amount of noise and halves the recommended amount of exposure time.(9)

Prevention hearing loss in occupational health

To prevent noise-induced hearing loss there are 6 steps which are(10) :

Identification and assessment of the risks from health hazards in the workplace. This involves

surveillance of the factors in the working environment and working practices which may

affect workers' health. It also requires a systematic approach to the analysis of occupational

"accidents", and occupational diseases.

Advising on planning and organisation of work and working practices, including the design

of work-places, and on the evaluation, choice and maintenance of equipment and on

substances used at work. In so doing, the adaptation of work to the worker is promoted.

Providing advice, information, training and education, on occupational health, safety and

hygiene and on ergonomics and protective equipment.

Surveillance of workers' health in relation to work.

Contributing to occupational rehabilitation and maintaining in employment people of

working age, or assisting in the return to employment of those who are unemployed for

reasons of ill health or disability.

Organising first aid and emergency treatment.

http://www.agius.com/hew/resource/rehab.htm

http://www.agius.com/hew/resource/surv.htm

http://www.agius.com/hew/resource/ergo.htm

http://www.agius.com/hew/resource/workenv.htm

CHAPTER IV

CONCLUTION

Danger of noise can cause hearing loss and irreversible reversible.

Therefore we must do a better prevention and treatment of hearing loss that occurs is not

getting worse.

Besides it takes the awareness and cooperation of the company nor the workers themselves

about the benefits and occupational health procedures.

Early awareness would prevent damage which will ultimately affect the quality of life.

BIBLIOGRAPHY

1. History of Occupational Safety and Health in Indonesia ; by Safe Design, 2000;

available at http://safe.gq.nu/safstory.html

2. Myers M; Chapter on Agriculture and Natural Resource Based Industries; in ILO

Encyclopaedia of Occupational Health and Safety ; Fourth Edition; Stellman JM

(Ed); Vol. III; the ILO; Geneva; 1998

3. National Safety Council of Indonesia, K3; Keselamatan dan Kesehatan Kerja di

Indonesia 1900-2000 ; Dewan Keselamatan dan Kesehatan Kerja National; 2000

4. Social Security and Coverage for all: Restructuring the Social Security System in

Indonesia – Issues and options , ILO, Jakarta 2002.

5. ASEAN OSHNET Occupational Safety and Health Network ; 2003; available at

http://www.asean-osh.net/

6. Daniel E. 2007. Noise and hearing loss: a review. The Journal of school health 77: 225-31

7. Warta Kesehatan Kerja ; Media Komunikasi Kesehatan Kerja; No. 1, 2002. Newsletter A published by the Occupational

8. The Department of Health, Indonesia; Strategic Planning of Occupational Health

Programme 2002 – 2004 ; 2002

9. Strategy for the Improvement of OSH and Working Conditions ; Report of an ILO

Advisory Mission and Proceedings of a National Workshop, Jakarta 16-17, May 1995

10. The ILO-IPEC Footwear Programme Team; Markkanen P; Improving Safety, Health,

and Productivity in the Informal Footwear Sector ; the ILO-IPEC; 2002

Hypogonadism and Diabetes Mellitus in Adult Male

BRILLI BAGUS DIPO

030.09.0049

JAKARTA 2012

ABSTRACT

In recent years concepts are developing whether male hypogonadism and testosterone

deficiency are the factors for developing insulin resistance and subsequent development of

type 2 diabetes mellitus. This hypothesis developed from the observations that, testosterone

deficiency in adult male is associated with type 2 diabetes mellitus, coronary artery disease

and heart failure. Replacement of testosterone hormone to this subset of patients results in

improvement of the condition. Recent studies have shown that male hypogonadism is more

prevalent than thought earlier, is strongly associated with metabolic syndrome and may be a

risk factor for the development of type 2 diabetes mellitus and coronary artery disease. Long-

term studies are required to establish the relation with these diseases, the effect of

testosterone replacement and its long-term safety profile with the exception of increase in

haematocrit, which already we know.

The prevalence of both hypogonadism and type 2 diabetes mellitusincreases with age.

But it is not proved beyond doubt, whether male hypogonadism contributes to the

development of type 2 diabetes mellitus or type 2 diabetes mellitus leads to the development

of hypogonadism or both are the presentations of some age related condition like increased

fat mass. This concept, if it is supported by large multicentric studies, a new arena of

understanding, treating and preventing diabetes mellitus in men will be opened.

Keywords : Hypogonadism, type 2 diabetes mellitus

INTRODUCTION

Testosterone is the key male hormone. It regulates a man's libido (sex drive) and the

development of secondary male sex characteristics, such as facial and body hair, the testes

and the penis. Testosterone also protects the health of bone and muscle tissues. Testosterone

deficiency is associated with many chronic health conditions, including type 2 diabetes

mellitus and other metabolic disorders.

Testosterone deficiency has been estimated to affect about 1 in 200 Australian men,

although this may under-represent the true number due to not all cases being diagnosed. In

men from Boston, USA, testosterone deficiency was found to affect about 1 in 18 men aged

30–79 years, but in men aged 60–79 this increased to about 1 in 8. Significantly, there is also

a strong association between testosterone deficiency and diabetes. A study in the United

Kingdom found that 42% of men with type 2 diabetes also had low or borderline levels of

testosterone..

DISCUSSION

Hypogonadism

Definition

Male hypogonadism is a condition in which the body doesn't produce enough

testosterone, the hormone that plays a key role in masculine growth and development during

puberty. You may be born with male hypogonadism, or it can develop later in life from injury

or infection. The effects depend on the cause and at what point in your life male

hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone

replacement therapy.

Symptoms

In adult males, hypogonadism may alter certain masculine physical characteristics and

impair normal reproductive function. Signs and symptoms may include:

Erectile dysfunction

Infertility

Decrease in beard and body hair growth

Decrease in muscle mass

Development of breast tissue (gynecomastia)

Loss of bone mass (osteoporosis)

Hypogonadism can also cause mental and emotional changes. As testosterone decreases,

some men may experience symptoms similar to those of menopause in women. These may

include:

Fatigue

Decreased sex drive

Difficulty concentrating

Hot flashes

Ethiology and Pathogenesis

Male hypogonadism means the testicles don't produce enough of the male sex

hormone testosterone. There are two basic types of hypogonadism:

Primary

This type of hypogonadism — also known as primary testicular failure — originates

from a problem in the testicles.

Secondary

This type of hypogonadism indicates a problem in the hypothalamus or the pituitary

gland — parts of the brain that signal the testicles to produce testosterone. The

hypothalamus produces gonadotropin-releasing hormone, which signals the

pituitarygland to make follicle-stimulating hormone (FSH) and luteinizing hormone.

Luteinizing hormone then signals the testes to produce testosterone.

Either type of hypogonadism may be caused by an inherited (congenital) trait or something

that happens later in life (acquired), such as an injury or an infection.

Primary hypogonadism

Common causes of primary hypogonadism include:

Klinefelter syndrome

This condition results from a congenital abnormality of the sex chromosomes, X and Y. A

male normally has one X and one Y chromosome. In Klinefelter syndrome, two or more X

chromosomes are present in addition to one Y chromosome. The Y chromosome contains the

genetic material that determines the sex of a child and related development. The extra X

chromosome that occurs in Klinefelter syndrome causes abnormal development of the

testicles, which in turn results in underproduction of testosterone.

Undescended testicles

Before birth, the testicles develop inside the abdomen and normally move down into their

permanent place in the scrotum. Sometimes one or both of the testicles may not be descended

at birth. This condition often corrects itself within the first few years of life without

treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and

reduced production of testosterone.

Mumps orchitis

If a mumps infection involving the testicles in addition to the salivary glands (mumps

orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur.

This may affect normal testicular function and testosterone production.

Hemochromatosis

Too much iron in the blood can cause testicular failure or pituitary gland dysfunction

affecting testosterone production.

Injury to the testicles

Because they're situated outside the abdomen, the testicles are prone to injury. Damage to

normally developed testicles can cause hypogonadism. Damage to one testicle may not

impair total testosterone production.

Cancer treatment

Chemotherapy or radiation therapy for the treatment of cancer can interfere with

testosterone and sperm production. The effects of both treatments often are temporary, but

permanent infertility may occur. Although many men regain their fertility within a few

months after treatment ends, preserving sperm before starting cancer therapy is an option that

many men consider.

Secondary hypogonadism

In secondary hypogonadism, the testicles are normal but function improperly due to a

problem with the pituitary or hypothalamus. A number of conditions can cause secondary

hypogonadism, including:

Kallmann syndroms

Abnormal development of the hypothalamus — the area of the brain that controls the

secretion of pituitary hormones — can cause hypogonadism. This abnormality is also

associated with impaired development of the ability to smell (anosmia) and red-green color

blindness.

Pituitary disorders

An abnormality in the pituitary gland can impair the release of hormones from the

pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or

other type of brain tumor located near the pituitary gland may cause testosterone or other

hormone deficiencies. Also, the treatment for a brain tumor, such as surgery or radiation

therapy, may impair pituitary function and cause hypogonadism.

Inflammatory disease

Certain inflammatory diseases, such as sarcoidosis, histiocytosis and tuberculosis, involve

the hypothalamus and pituitary gland and can affect testosterone production, causing

hypogonadism.

HIV/AIDS

HIV/AIDS can cause low levels of testosterone by affecting the hypothalamus, the

pituitary and the testes.

Medications

The use of certain drugs, such as opiate pain medications and some hormones, can affect

testosterone production.

Obesity

Being significantly overweight at any age may be linked to hypogonadism.

Normal aging

Older men generally have lower testosterone levels than younger men do. As men age,

there's a slow and continuous decrease in testosterone production. The rate at which

testosterone declines varies greatly among men. As many as 30 percent of men older than 75

have a testosterone level that's below normal, according to the American Association of

Clinical Endocrinologists.

Hypogonadism and Aging

Several studies have established the proportionate fall of testosterone with age. Total

testosterone (TT) in circulation consist of:

Sex Hormone Binding Globulin (SHBG) bound testosterone (SHBG-TE) = 58%

Albumin bound testosterone (ABT) = 40%

Free testosterone (FT) = 2%

Age related fall in total testosterone with increase in SHBG level and decrease in

bioavailable free testosterone has been observed even if Body Mass Index (BMI) does not

exceed 26 kg/m2 Feldmaen, observed a decline of total testosterone by 0.8% per year of age,

whereas both free and albumin bound testosterone declines at about 2% per year. SHBG

levels increased at 1.6% per year. But luteinizing hormone (LH) and follicle stimulating

hormone (FSH) levels tend to rise with age.

Observed the fact that the major age related changes in testosterone levels are caused

by changes at testicular function and not due to hypothalamic pituitary axis pathway, which is

not altered with age. They noted that treatment of aging men with clomiphene citrate, an anti-

estrogen agent, could not increase the level of bioavailable testosterone as is seen in younger

men even though LH pulse characteristics and bioavailable LH levels were similar in two

groups.

Diagnosis

Because symptoms are nonspecific in nature, a complete history, physical

examination, and laboratory analysis must accompany the clinical presentation for diagnosis.

A history that focuses on developmental milestones will help the clinician determine the

onset of the disorder. Possible causes must also be ruled out during a patient history, such as

exposure to environmental toxins, medications that have been associated with the disorder, or

evidence of a congenital cause such as Klinefelter's syndrome or pituitary gland hormone

deficiency. In addition, patients should be asked about recreational drug use, eating disorders,

and excessive exercise, as all of these can transiently alter testosterone levels.

If clinical symptoms are present, serum testosterone levels should be measured. The

total testosterone level should be the first measurement taken to determine hypogonadic state.

It should be drawn between the hours of 8 am and 11 am to ensure that a peak level is

captured (diurnal fluctuations can occur throughout the day, especially in younger men). If

an abnormal laboratory value is identified, a confirmatory measurement should be performed

to ensure that the diagnosis is appropriate. It has been reported that up to 30% of patients with

a low testosterone level upon initial laboratory measurement have a normal level upon repeat

measurement. Numerous factors can transiently alter testosterone levels, including time of

measurement (day and year), medications, and acute illness.

In most references, a total testosterone level <300 ng/mL is considered low; however,

some controversy surrounds the inconsistency with measurement assays in determining this

reference range. Free testosterone should be measured if it is suspected that the patient may

have alterations in his sex hormone–binding globu lin (SHBG). Testosterone is highly bound

to SHBG and albumin; thus, when SHBG concentrations are significantly affected,

circulating testosterone levels can be as well. Many things can cause alterations in SHBG

concentrations, some of which include obesity, nephrotic syndrome, hypothyroidism, and use

of glucocorticoids, progestins, and androgenic steroids. Conditions associated with increased

levels of SHBG include aging, hepatic cirrhosis, hyperthyroidism, HIV, and use of

anticonvulsants or estrogens. The lower limit of normal when discussing free testosterone is

typically 50 pg/mL.

Other laboratory measurements that should be completed if testosterone levels return

low include measurement of LH and FSH. These stimulatory hormones help clinicians

determine whether the identified hypogonadism is of primary or secondary nature. As

described previously, primary or hypergonadotropic hypogonadism would demonstrate an

elevation in these hormones, signifying adequate pituitary function. On the other hand, if LH

and FSH levels are low, a suspected pituitary cause must be considered, with further imaging

necessary to rule out structural abnormalities.

Type 2 Diabetes Mellitus

Definition

Type 2 diabetes, once known as adult-onset or noninsulin-dependent diabetes, is

caused by the body’s ineffective use of insulin. It often results from excess body weight and

physical inactivity.With type 2 diabetes, your body either resists the effects of insulin — a

hormone that regulates the movement of sugar into your cells — or doesn't produce enough

insulin to maintain a normal glucose level. Untreated, type 2 diabetes can be life-threatening.

There's no cure for type 2 diabetes, but you can manage — or even prevent — the condition.

Start by eating well, exercising and maintaining a healthy weight. If diet and exercise aren't

enough to control your type 2 diabetes, you may need diabetes medications or insulin therapy

to manage your blood sugar.

Symptoms

Type 2 diabetes symptoms may develop very slowly. In fact, you can have type 2

diabetes for years and not even know it. Look for:

Increased thirst and frequent urination.

As excess sugar builds up in your bloodstream, fluid is pulled from the tissues. This

may leave you thirsty. As a result, you may drink — and urinate — more than usual.

Increased hunger.

Without enough insulin to move sugar into your cells, your muscles and organs

become depleted of energy. This triggers intense hunger.

Weight loss.

Despite eating more than usual to relieve hunger, you may lose weight. Without the

ability to metabolize glucose, the body uses alternative fuels stored in muscle and fat.

Calories are lost as excess glucose is released in the urine.

Fatigue.

If your cells are deprived of sugar, you may become tired and irritable.

Blurred vision.

If your blood sugar is too high, fluid may be pulled from the lenses of your eyes. This

may affect your ability to focus clearly.

Slow-healing sores or frequent infections.

Type 2 diabetes affects your ability to heal and resist infections.

Areas of darkened skin.

Some people with type 2 diabetes have patches of dark, velvety skin in the folds and

creases of their bodies — usually in the armpits. This condition, called acanthosis

nigricans, may be a sign of insulin resistance.

Causes

Type 2 diabetes develops when the body becomes resistant to insulin or when the

pancreas stops producing enough insulin. Exactly why this happens is unknown, although

excess weight and inactivity seem to be contributing factors.

Insulin is a hormone that comes from the pancreas, a gland situated just behind and

below the stomach. When you eat, the pancreas secretes insulin into the bloodstream. As

insulin circulates, it acts like a key by unlocking microscopic doors that allow sugar to enter

your cells. Insulin lowers the amount of sugar in your bloodstream. As your blood sugar level

drops, so does the secretion of insulin from your pancreas.

Glucose — a sugar — is a main source of energy for the cells that make up muscles

and other tissues. Glucose comes from two major sources: the food you eat and your liver.

After intestinal digestion and absorption, sugar is absorbed into the bloodstream. Normally,

sugar then enters cells with the help of insulin.

The liver acts as a glucose storage and manufacturing center. When your insulin

levels are low — when you haven't eaten in a while, for example — the liver metabolizes

stored glycogen into glucose to keep your glucose level within a normal range.

In type 2 diabetes, this process works improperly. Instead of moving into your cells,

sugar builds up in your bloodstream. This occurs when your pancreas doesn't make enough

insulin or your cells become resistant to the action of insulin.

Pathophysiology

Type 2 diabetes is characterized by a combination of peripheral insulin resistance and

inadequate insulin secretion by pancreatic beta cells. Insulin resistance, which has been

attributed to elevated levels of free fatty acids and proinflammatory cytokines in plasma,

leads to decreased glucose transport into muscle cells, elevated hepatic glucose production,

and increased breakdown of fat.

A role for excess glucagon cannot be underestimated; indeed, type 2 diabetes is an

islet paracrinopathy in which the reciprocal relationship between the glucagon-secreting

alpha cell and the insulin-secreting beta cell is lost, leading to hyperglucagonemia and hence

the consequent hyperglycemia.

For type 2 diabetes mellitus to occur, both insulin resistance and inadequate insulin

secretion must exist. For example, all overweight individuals have insulin resistance, but

diabetes develops only in those who cannot increase insulin secretion sufficiently to

compensate for their insulin resistance. Their insulin concentrations may be high, yet

inappropriately low for the level of glycemia.

A simplified scheme for the pathophysiology of abnormal glucose metabolism in type 2

diabetes mellitus is depicted in the image below.

With prolonged diabetes, atrophy of the pancreas may occur. A study by Philippe et al

used computed tomography (CT) scan findings, glucagon stimulation test results, and fecal

elastase-1 measurements to confirm reduced pancreatic volume in individuals with a median

15-year history of diabetes mellitus (range, 5-26 years). This may also explain the associated

exocrine deficiency seen in prolonged diabetes.

How does insulin resistance affect testosterone levels?

Testosterone production is affected in diabetic men because they have higher than

normal concentrations of glucose in their blood. When blood glucose levels are high, the

pituitary gland produces less LH than it normally would. As testosterone is only produced

whenLH is secreted from the pituitary, this reduces the amount of testosterone produced by a

man's body.

The association between diabetes and hypogonadism are interdependent – that is, they

work both ways. Low testosterone is a risk factor for diabetes and the metabolic syndrome

because testosterone levels affect body fat composition, glucose transport and the ways in

which the body's cells use testosterone. Diabetes is also a risk factor for hypogonadism

because it is associated with increased body mass and altered hormone profiles (e.g. reduced

LH as a result of high blood glucose levels, which in turn reduces testosterone levels).

Diagnosis

Diagnostic criteria by the American Diabetes Association (ADA) includes the following:

A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or

A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g

oral glucose tolerance test (OGTT), or

A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with

classic symptoms of hyperglycemia or hyperglycemic crisis

Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher should be a primary

diagnostic criterion or an optional criterion remains a point of controversy.

Indications for diabetes screening in asymptomatic adults includes the following:

Sustained blood pressure >135/80 mm Hg

Overweight and 1 or more other risk factors for diabetes (eg, first-degree relative with

diabetes, BP >140/90 mm Hg, and HDL < 35 mg/dL and/or triglyceride level >250

mg/dL)

ADA recommends screening at age 45 years in the absence of the above criteria

The Correlation between Hypogonadism and Type 2 Diabetes Mellitus

The association between low levels of testosterone (a condition known as

hypogonadism) and type 2 diabetes mellitus are well recognised, but it also appears that

testosterone deficiency is common in men with diabetes regardless of type. Metabolic

syndrome is a condition characterised by several co-occurring metabolic imbalances (e.g.

impaired insulin metabolism, obesity, high blood pressure); it often procedes type 2 diabetes

mellitus, and is also associated with testosterone deficiency. There is considerable evidence

that men with metabolic syndrome are more likely to develop hypogonadism. Testosterone

replacement therapy has been shown to improve insulin metabolism.

Testosterone and testosterone metabolism

In men, testosterone is primarily produced by the Leydig cells of the testes.

Testosterone production in the testes is stimulated when a man's pituitary gland produces a

hormone called luteinising hormone (LH). If either the pituitary gland or the testes are

dysfunctional, testosterone production may decline or stop, leading to testosterone deficiency

or hypogonadism.

Insulin and insulin metabolism

Insulin is a hormone produced by the pancreas and functions to lower levels of

glucose in the blood. If the body does not produce enough insulin, or if the insulin produced

does not function properly to reduce blood glucose, levels of blood glucose rise and lead to

health conditions such as metabolic syndrome and type 1 and type 2 diabetes mellitus.

Evidence of the associations between diabetes, metabolic syndrome and testosterone

deficiency

Studies have reported that 20–64% of men with testosterone

deficiency/hypogonadism also have type 2 diabetes. The proportion of men who have both

type 2 diabetes mellitus and hypogonadism increases in older groups of men.

Men who have slightly reduced testosterone concentrations (but not low enough to be

considered testosterone deficient) are also more likely to have low insulin (and high blood

glucose) levels. Therapies that reduce testosterone levels (e.g. androgen deprivation therapy,

which is used by men with prostate cancer because testosterone stimulates the growth of

prostate cancer) have also been shown to lower insulin levels.

Men with low testosterone concentrations, in addition to having lower insulin levels,

are more likely to develop the metabolic syndrome or one of the metabolic imbalances that

characterise it (e.g. impaired insulin metabolism, obesity, high blood pressure). Scientists

have even suggested that hypogonadism should be considered one of the imbalances that

characterise metabolic syndrome.

Evidence shows that approximately one third of type 2 diabetics are testosterone

deficient. An even greater proportion of men who are both diabetic and obese experience

testosterone deficiency, and the likelihood of testosterone deficiency increases as type 2

diabetes progresses or worsens.

There is also evidence of an association between insulin resistance, glucose levels,

abdominal obesity and free testosterone levels in type 1 diabetic men. Abdominal obesity

appears to play a particularly important role in these relationships. Abdominal obesity causes

insulin resistance, which in turn reduces testosterone levels because it increases the amount of

testosterone converted to estradiol.

Increasing knowledge about the associations between testosterone deficiency and

diabetes have lead to trialling testosterone replacement therapy (TRT) as a treatment for

insulin resistance in diabetic men. Evidence to date shows that TRT improves insulin

metabolism in hypogonadal diabetic men.

Assessing and managing lifestyle risk factors

In addition to starting TRT, it is important for hypogonadal men with metabolic

conditions to manage modifiable lifestyle factors, as an unhealthy lifestyle may make their

metabolic conditions worse and also reduce the effectiveness of their treatment. Lifestyle

factors play an important role in the development of type 2 diabetes mellitus, metabolic

syndrome and testosterone deficiency. In particular, low levels of physical activity, unhealthy

eating habits (e.g. eating too much, consuming too much fat and sugar), smoking and obesity

increase the risk of each of these conditions. The risk of testosterone deficiency in men with

diabetes increases further if they are also obese. Men with diabetes who maintain a healthy

lifestyle may prevent the onset of testosterone deficiency.

CONCLUSION

Multiple studies have shown that testosterone deficiency in men is associated with

Type 2 diabetes and metabolic syndrome, coronary artery disease and heart failure.

Testosterone replacement has also shown to improve the above conditions. But in absence of

large long duration multicentric studies, we cannot allow hypogonadism to join as a family

member of metabolic syndrome at present, and cannot also allow routine recommendation of

testosterone replacement to treat or prevent metabolic syndrome or diabetes mellitus. But

physicians should be mindful to screen for metabolic syndrome and diabetes mellitus in all

cases of hypogonadism. As an isolated case, they can try testosterone replacement after

discussing with the patient regarding advantages and disadvantages more so, in cases of

sexual dysfunction and develop a novel approach. But watch for complications like

erythrocytosis and prostatic carcinoma should always guide these approaches. This new

concept also indulges us to think whether female sex hormone has got any equivalent role in

women or not.

REFERENCES

1. Kalyani RR, Dobs AS. Androgen deficiency, diabetes and the metabolic syndrome in

men. Curr Opin Endocrinol Diabetes Obes. 2007;14(3):226-34.

2. American Association of Clinical Endocrinologists Hypogonadism Task Force.

American Association of Clinical Endocrinologists medical guidelines for clinical

practice for the evaluation and treatment of hypogonadism in adult male patients—

2002 update. Endocr Pract 2002;8:439-56.

3. Miner MM, Seftel AD. Testosterone and Ageing: what have we learned since the

institute if medicine report and what lies ahead? Int J Clin Pract. 2007;61(4):622-32.

4. Tan RS, Pu SJ. Impact of obesity on hypogonadism in the andropause. Int J Androl

2002;25:195-201.

5. Kapoor D, Malkin CJ. Channer KS, Jones TH. Androgens, insulin resistance and

vascular disease in men. Clinical Endocrinology 2005:239-50.

6. Simon D, Charles MA, Lahlou N, et al. Androgen therapy improves insulin sensitivity

and decreases leptin level in healthy adult men with low plasma total testosterone: a

3-month randomized placebo-controlled trial [letter]. Diabetes Care 2001.

7. Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic

syndrome. Nat Rev Endocrinol. 2009;5(12):673-81.

8. Diabetes statistics. American Diabetes Association. http://www.diabetes.org/diabetes-

basics/diabetes-statistics. Accessed Dec. 10, 2012.

9. Allan CA, McLachlan RI. Testosterone deficiency in men: Diagnosis and

management. Aust Fam Physician. 2003;32(6):422-7.

10. Traish AM, Guay A, Feeley R, Saad F. The dark side of testosterone deficiency:

Metabolic syndrome and erectile dysfunction. J Androl. 2009;30(1):10-22.

11. McCulloch DK. Initial management of blood glucose in type 2 diabetes mellitus.

http://www.uptodate.com/home/index.html. Accessed Dec. 18, 2012.

12. Miner MM, Sadovsky R. Evolving issues in male hypogonadism: Evaluation,

management and comorbidities. Cleve Clin J Med. 2007;74(Suppl 3):S38-46.

13. Grossman M, Thomas MC, Panagiotopoulos S, et al. Low testosterone levels are

common and associated with insulin resistance in men with diabetes. J Clin

Endocrinol Metab. 2008;93(5):1834-40.

14. Shabsigh R, Arver S, Channer KS, et al. The triad of erectile dysfunction,

hypogonadism and the metabolic syndrome. Int J Clin Pract. 2008;62(5):791-8.

The Management of Asthma in Diabetes

Written by:

Christopher Roswell P. Siagian

030. 09. 053

FACULTY OF MEDICINE

TRISAKTI UNIVERSITY

JAKARTA, DECEMBER 2012

ABSTRACT

Asthma is a syndrome characterized by airflow obstruction that varies markedly,

both spontaneously and with treatment, and is one of the three chronic obstructive pulmonary

diseases besides chronic bronchitis and emphysema. The process involves in asthma is an

inflammation that leads to three events: bronchoconstriction, hypersecretion of mucus, and

swollen of bronchi. Diabetes is a disease in which blood glucose, or sugar, levels are too

high. Glucose comes from the foods. Insulin is a hormone that helps the glucose get into the

cells to give them energy. With type 1 diabetes, the body does not make insulin. With type 2

diabetes, the more common type, the body does not make or use insulin well. Without enough

insulin, the glucose stays in the blood. In diabetes, the patient becomes vulnerable to

microorganisms infections because the reduced of immunity. One of the treatments

commonly used in asthma is corticosteroid, either oral or inhaled. These drugs which are

classified in steroid class have an effect in suppressing the immune system, thus increasing

the risk of infection and also increase blood sugar. The issue in managing asthma in diabetes

is how to relieve the asthma symptoms in patient without worsening the pre-existing diabetes.

Keywords: asthma, diabetes, corticosteroid, blood glucose

CHAPTER I

INTRODUCTION

Asthma affects 5-10% of the population or an estimated 23.4 million persons,

including 7 million children. The overall prevalence rate of exercise-induced bronchospasm

is 3-10% of the general population if persons who do not have asthma or allergy are

excluded, but the rate increases to 12-15% of the general population if patients with

underlying asthma are included. Asthma affects an estimated 300 million individuals

worldwide. Annually, the World Health Organization (WHO) has estimated that 15 million

disability-adjusted life-years are lost and 250,000 asthma deaths are reported worldwide. (1)

The management of asthma differs according to the classification of severity.

Corticosteroids may be used from mild to severe – persistent asthma, ranging from low dose

with alternative medicines to high dose and its combinations.Although use of systemic

corticosteroids is recommended early in the course of acute exacerbations in patients with an

incomplete response to beta agonists, oral administration is equivalent in efficacy to

intravenous administration. Corticosteroids speed the resolution of airway obstruction and

prevent a late-phase response.(1,2)

Diabetes is a chronic disease, which occurs when the pancreas does not produce

enough insulin, or when the body cannot effectively use the insulin it produces. This leads to

an increased concentration of glucose in the blood (hyperglycaemia).Type 1 diabetes

(previously known as insulin-dependent or childhood-onset diabetes) is characterized by a

lack of insulin production.Type 2 diabetes (formerly called non-insulin-dependent or adult-

onset diabetes) is caused by the body’s ineffective use of insulin. It often results from excess

body weight and physical inactivity.(3)

Rates of diabetes are increasing worldwide. The International Diabetes Federation

predicts that the number of people living with diabetes will to rise from 366 million in 2011

to 552 million by 2030.The top 10 countries in number of people with diabetes are currently

India, China, the United States, Indonesia, Japan, Pakistan, Russia, Brazil, Italy, and

Bangladesh.(4)

Patient with diabetes has impaired immunity which leads to high risk from

infections. In the following chapter we will be talking about the necessity of using

corticosteroids for asthma in diabetes.

CHAPTER II

LITERATURE REVIEW

I. Asthma

Asthma is best described as a chronic disease that involves inflammation of the

pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression

of a lower airway obstruction that usually is reversible. Asthma is characterised by a specific

pattern of inflammation that is largely driven viaimmunoglobulin (Ig)E-dependent

mechanisms. Genetic factors have an importantinfluence on whether atopy develops and

several genes have now been identified.Mostof the genetic linkages reported for asthma are

common to all allergic diseases.However, environmental factors appear to be more important

in determining whether anatopic individual develops asthma, although genetic factors may

exert an influence onhow severely the disease is expressed and the amplification of the

inflammatory response.(5,6)

I. A. Etiology

Genetics

Genome-wide linkage studies and case–control studies have identified 18 genomic

regions and more than 100 genes associated with allergy and asthma in 11 different

populations. In particular, there are consistently replicated regions on the long arms of

chromosomes 2, 5, 6, 12 and 13. Association studies of unrelated individuals have also

identified more than 100 genes associated with allergy and asthma, 79 of which have been

replicated in at least one further study.A recent genome-wide association study identified a

new gene, ORMDL3, that exhibited a highly significantly association with asthma (p < 10−12)

(for single nucleotide polymorphism rs8067378, odds ratio 1.84, 95% confidence interval

1.43–2.42) a finding that has now been replicated in several populations. (7,8,9,10)

Stress

A number of animal models have suggested that prenatal maternal stress acts

through regulation of the offspring’s hypothalamic–pituitary–adrenal axis to decrease cortisol

levels, which may affect the development of an allergic phenotype. Although there is a

correlation between caregiver stress early in the infant’s life and higher levels of

immunoglobulin E in the infant and early wheezing, no studies to date have shown an

association with asthma.(11.12)

Obesity

A study by Cottrell et al explored the relationship between asthma, obesity, and

abnormal lipid and glucose metabolism. The study found that community-based data linked

asthma, body mass, and metabolic variables in children. Specifically, these findings described

a statistically significant association between asthma and abnormal lipid and glucose

metabolism beyond body mass association.Accelerated weight gain in early infancy is

associated with increased risks of asthma symptoms according to one study of preschool

children. (1)

Other etiologies include environmental allergens, viral respiratory tract infections,

exercise, hyperventilation, gastroesophageal reflux disease, chronic sinusitis or rhinitis,

aspirin or nonsteroideal anti-inflammatory drug (NSAID) hypersensitivity, sulfite sensitivity,

use of beta-adrenergic receptor blockers, environmental pollutants, tobacco smoke,

occupational exposure, irritants and perinatal factors. (1)

I. B. Pathophysiology

The pathophysiology of asthma can be divided into four events: bronchoconstriction,

airway edema, airway hyperresponsiveness and airway remodeling. (13)

Bronchoconstriction

In asthma, the dominant physiological event leading to clinical symptoms is airway

narrowing and a subsequent interference with airflow. In acute exacerbations of asthma,

bronchial smooth muscle contraction (bronchoconstriction) occurs quickly to narrow the

airways in response to exposure to a variety of stimuli including allergens or irritants.

Allergen-induced acute bronchoconstriction results from an IgE-dependent release of

mediators from mast cells that includes histamine, tryptase, leukotrienes, and prostaglandins

that directly contract airway smooth muscle.(13)

Airway edema

As the disease becomes more persistent and inflammation more progressive, other

factors further limit airflow. These include edema, inflammation, mucus hypersecretion and

the formation of inspissated mucus plugs, as well as structural changes including hypertrophy

and hyperplasia of the airway smooth muscle.(13)

Airway hyperresponsiveness

Airway hyperresponsiveness—an exaggerated bronchoconstrictor response to a wide

variety of stimuli—is a major, but not necessarily unique, feature of asthma. The degree to

which airway hyperresponsiveness can be defined by contractile responses to challenges with

methacholine correlates with the clinical severity of asthma. The mechanisms influencing

airway hyperresponsiveness are multiple and include inflammation, dysfunctional

neuroregulation, and structural changes; inflammation appears to be a major factor in

determining the degree of airway hyperresponsiveness. Treatment directed toward reducing

inflammation can reduce airway hyperresponsiveness and improve asthma control.(13)

Airway remodeling

In some persons who have asthma, airflow limitation may be only partially

reversible. Permanent structural changes can occur in the airway; these are associated with a

progressive loss of lung function that is not prevented by or fully reversible by current

therapy. Airway remodeling involves an activation of many of the structural cells, with

consequent permanent changes in the airway that increase airflow obstruction and airway

responsiveness and render the patient less responsive to therapy. These structural changes can

include thickening of the sub-basement membrane, subepithelial fibrosis, airway smooth

muscle hypertrophy and hyperplasia, blood vessel proliferation and dilation, and mucous

gland hyperplasia and hypersecretion.(13)

I. C. Treatment

The goal of asthma treatment is to achieve and maintainclinical control. Medications

to treat asthma can beclassified as controllers or relievers.The following will discussed only

about the role of glucocorticosteroids in treating asthma. (14)

I. C. 1. Controllers

Inhaled glucocorticosteroids

Inhaled glucocorticosteroids are currentlythe most effective anti-inflammatory

medications for thetreatment of persistent asthma. Studies have demonstratedtheir efficacy in

reducing asthma symptoms, improvingquality of life, improving lung function, decreasing

airwayhyperresponsiveness,controlling airway inflammation,reducing frequency and severity

of exacerbations, andreducing asthma mortality. However, they do not cureasthma, and when

they are discontinued deterioration ofclinical control follows within weeks to months in

aproportion of patients.(14)

Systemic glucocorticosteroids

Long-term oral glucocorticosteroidtherapy (that is, for periods longer than two

weeks as aglucocorticosteroid “burst”) may be required for severelyuncontrolled asthma, but

its use is limited by the risk ofsignificant adverse effects. The therapeutic index(effect/side

effect) of long-term inhaled glucocorticosteroidsis always more favorable than long-term

systemicglucocorticosteroids in asthma. If oral glucocorticosteroidshave to be administered

on a long-term basis,attention must be paid to measures that minimize thesystemic side

effects. Oral preparations are preferred overparenteral (intramuscular or intravenous) for

long-termtherapy because of their lower mineralocorticoid effect,relatively short half-life,

and lesser effects on striatedmuscle, as well as the greater flexibility of dosing that

permitstitration to the lowest acceptable dose that maintains control.(14)

Other controllers are leukotriene modifiers, theophylline, long-acting inhaled and

oral β2 agonists, anti Ig-E, allergen-specific immunotherapy and oral anti-allergic compounds.

I. C. 2. Relievers

Systemic glucocorticosteroid

Although systemic glucocorticosteroidsare not usually thought of as reliever

medications, they areimportant in the treatment of severe acute exacerbationsbecause they

prevent progression of the asthmaexacerbation, reduce the need for referral to

emergencydepartments and hospitalization, prevent early relapseafter emergency treatment,

and reduce the morbidity of theillness. The main effects of systemic glucocorticosteroidsin

acute asthma are only evident after 4 to 6 hours. Oraltherapy is preferred and is as effective as

intravenoushydrocortisone. A typical short course of oral glucocorticosterodsfor an

exacerbation is 40-50 mgprednisolone given daily for 5 to 10 days depending on theseverity

of the exacerbation. When symptoms havesubsided and lung function has approached the

patientʼspersonal best value, the oral glucocorticosteroids can bestopped or tapered, provided

that treatment with inhaledglucocorticosteroids continues. Intramuscular injectionof

glucocorticosteroids has no advantage over a shortcourse of oral glucocorticosteroids in

preventing relapse.(14)

II. Diabetes

Diabetes is a chronic disease, which occurs when the pancreas does not produce

enough insulin, or when the body cannot effectively use the insulin it produces. This leads to

an increased concentration of glucose in the blood (hyperglycaemia).(3)

II. A. Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (DM) is a multisystem disease with both biochemical and

anatomic/structural consequences. It is a chronic disease of carbohydrate, fat, and protein

metabolism caused by the lack of insulin, which results from the marked and progressive

inability of the pancreas to secrete insulin because of autoimmune destruction of the beta

cells.(3)

Pathophysiology

Type 1 diabetes usually develops as a result of autoimmune pancreatic beta-cell

destruction in genetically susceptible individuals. Up to 90% of patients will have

autoantibodies to at least one of 3 antigens: glutamic acid decarboxylase (GAD); insulin; and

a tyrosine-phosphatase-like molecule, islet auto-antigen-2 (IA-2).Beta-cell destruction

proceeds sub-clinically for months to years as insulitis (inflammation of the beta cell). When

80% to 90% of beta cells have been destroyed, hyperglycaemia develops. Insulin resistance

has no role in the pathophysiology of type 1 diabetes. However, with increasing prevalence of

obesity, some type 1 diabetic patients may be insulin resistant in addition to being insulin

deficient.(15)

II. B. Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is a progressive disorder defined by deficits in insulin secretion

and action that lead to abnormal glucose metabolism and related metabolic

derangements. Although the aetiologies of type 1 and type 2 diabetes differ dramatically,

both lead to hyperglycaemic states, and both share common macrovascular (coronary heart,

cerebrovascular, and peripheral vascular disease) and microvascular (retinopathy,

nephropathy, and neuropathy) complications. Type 2 diabetes is usually diagnosed based on

screening. It is preceded by a state of pre-diabetes, which may be clinically detected by a

fasting plasma glucose of 5.6 mmol/L to 6.9 mmol/L (100 to 125 mg/dL). Diabetes diagnosis

is based on 2 confirmed values of: fasting plasma glucose >6.9 mmol/L (125 mg/dL); HbA1c

of 48 mmol/mol (6.5%) or greater; or (less commonly) abnormal glucose tolerance test

results, or a random plasma glucose of ≥200 mg/dL plus symptoms of hyperglycaemia.(16)

Pathophysiology

The precise mechanism by which the diabetic metabolic state leads to microvascular

and macrovascular complications is only partly understood but likely involves both

uncontrolled BP and uncontrolled glucose, increasing the risk of microvascular complications

such as retinopathy and nephropathy. Mechanisms may involve defects in aldose reductase

and other metabolic pathways, damage to tissues from accumulation of glycated end

products, and other mechanisms. With respect to macrovascular complications, high BP and

glucose raise risk, but so do lipid abnormalities and tobacco use. One unifying theory

postulates the existence of a metabolic syndrome that includes diabetes mellitus,

hypertension, dyslipidaemias, and obesity, and predisposes to coronary heart disease, stroke,

and peripheral artery disease. However, this theory is not universally accepted as more

clinically useful than assessing individual cardiovascular risk factors.(16)

\

Source: Taylor SI, Olefsky JM. Diabetes mellitus: a fundamental and clinical text. 3 rded. Philadelphia: Lippincott Williams & Wilkins; 2004.

Source: http://www.caninsulin.com/Pathophysiology-algorithm.htm

http://www.caninsulin.com/Pathophysiology-algorithm.htm

CHAPTER III

DISCUSSION

As seen in previous chapter, asthma can be determined in any of the following ways:

the underlying cause of asthma symptoms, severity of symptoms, and the way it’s controlled.

Source: .New York State Department of Health.Clinical guideline for the diagnosis, evaluation and management

of adults and children with asthma. Available at: http://www.nyhealth.gov. accessed on : December 1st 2012.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that involves the

progressive destruction of the insulin-producing beta cells in the islets of langerhans. It is a

http://www.nyhealth.gov/

complex process that results from the loss of tolerance to insulin and other beta-cell-specific

antigens. Various genetic and environmental factors have been studied so far, but precise

causation has yet to be established. Numerous studies in rodents and human subjects have

been performed in order to elucidate the role of B and T cells, which determine the risk of

development and progression of diabetes. These studies have demonstrated that while T1DM

is fundamentally a T-cell-mediated autoimmune response, the development of this disease

results from complex interactions between the adaptive and innate immune systems, with

numerous cell types thought to contribute to pathogenesis. Like any complex disease, the

variation in severity and incidence of T1DM can be attributed to a combination of genetic

and environmental factors.(17)

Source: Ting C, Bansal V, Batal I, Mounayar M, et al. Impairment of immune systems in diabetes. In: Diabetes:

an old disease, a new insight. Ahmad SI, editor. Texas: LANDES Bioscience; 2012.

Infectious diseases are common and serious complication of diabetes mellitus (DM)

and hyperglycemia. The increase of infections in patients with DM is known to depend upon

an immunosuppressive condition which is brought about by impaired innate immunity and

acquired immunity. For instance, functions of neutrophils such as phagocyte, chemotaxis and

cytokine-production are decreased in DM model mouse and hyperglycemia and a Th2-axis

shift which reduces Th1-dependent immunity are observed in DM patients. However, the

majority of results concerning interaction of hyperglycemia and immune function are

controversial and relevance of hyperglycemia and/or hyperinsulinemia to immunosuppressive

mechanisms remains unclear.(18)

High glucose levels lead to shunting through the polyol pathway, an increase in

diacylglycerol which activates protein kinase C, an increase in the release of electrons that

react with oxygen molecules to form superoxides, and the non-enzymatic glycosylation of

proteins that result in greater formation of advanced glycation end products. Each of these

can lead to aberrant cell signalling that affects innate immunity for example, by activating the

MAP kinase pathway or inducing activation of transcription factors such as NF-kappaB. This

may be a common feature of several complications including periodontal disease,

atherosclerosis, nephropathy, impaired healing and retinopathy. These complications are

frequently associated with increased expression of inflammatory cytokines such as TNF-

alpha, IL-1beta and IL-6 and enhanced generation of reactive oxygen species.(19)

Source: Graves DT, Kayal RA. Diabetic complications and dysregulated innate immunity. Front

Biosci2008;13:1227-1239.

In the management of asthma, inhaled corticosteroids (ICS) can be prescribed in low

dose in mild persistent to high dose ICS in severe persistent asthma. Whilst oral

corticosteroid is used to maintain control in severe persistent after the initiating treatment is

done. Most of the benefit from ICS is achieved in adults at low doses, equivalent to 400 ug of

budenoside per day. Increasing to higher doses provides little further benefit in terms of

asthma control but increases the risk of side effects. Current evidence suggest that in adults,

systemic effects of ICS are not a problem at doses of 400 ug or less budesonide or equivalent

daily. In long-term high doses however, side effects can occur such as cataract and

osteoporosis. It does not mention the correlation between ICS and blood glucose serum.(14)

In a study by Slatore CG, et all in side effect of inhaled corticosteroid in diabetic

subjects however; there is evidence in increasing blood glucose concentration by 1.82 mg/dL

in every additional 100 ug of ICS dose. On the other hand, oral corticosteroid has greater

impact in increasing blood glucose serum.(20)

Other study shows that moderately high dose ICS for treatment of asthma and

COPD is associated with small disturbances in glucose control after a relatively brief period

of therapy in diabetic subjects relative to oral montelukast therapy. The changes are

detectable but smaller than those that would be considered clinically significant, therefore

changing or stopping therapy is not necessary. Careful monitoring of blood glucose is

required when ICS therapy is initiated. In diabetics use of steroids may warrant adjusting or

increasing dose of anti-diabetic therapy. (21)

The systemic side effects of long-term oralor parenteral corticosteroidtreatment

includeosteoporosis, arterial hypertension, diabetes, hypothalamicpituitary-adrenal axis

suppression, obesity, cataracts,glaucoma, skin thinning leading to cutaneous striae andeasy

bruising, and muscle weakness. Patients with asthmawho are on long-term systemic

glucocorticosteroids in anyform should receive preventive treatment for osteoporosis.Caution

and close medical supervision are recommendedwhen considering the use of systemic

glucocorticosteroidsin patients with asthma who also have tuberculosis,parasitic infections,

osteoporosis, glaucoma, diabetes,severe depression, or peptic ulcers.(14)

CHAPTER IV

CONCLUSION

The pathophysiology of asthma involves four events: bronchoconstriction, airway

edema, airway hyperresponsiveness and airway remodeling. Management of asthma includes

prescription of inhaled corticosteroid or oral corticosteroid, ranging from low doses to high

doses depends on the severity of asthma. These medicines have effects in endocrine,

metabolic and immune system. Diabetes is characterized in increased blood glucose

concentration (hyperglycemia). Diabetic patient with asthma should be monitored carefully

because the side effects of corticosteroids medicine.

In conclusion, there are some important points:

Careful monitoring of blood glucose is required when ICS therapy is

initiated.

In diabetics use of steroids may warrant adjusting or increasing dose of anti-

diabetic therapy.

Caution and close medical supervision are recommendedwhen considering

the use of systemic glucocorticosteroidsin patients with asthma who also

have diabetes.

REFERENCES

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3. World Health Organization. Diabetes. Available at:http://www.who.int/topics/diabetes_mellitus/en/. Accessed on : December 1st 2012.

4. Khardori R. Type 2 Diabetes Mellitus. Available at: httP://emedicine.medscape.com/article/117853-overview#a0156. accessed on : December 1st 2012.

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6. Barnes PJ. Pathophysiology of asthma. Available at:

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7. Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery.

Genes Immun 2006;7:95-100.

8. Moffat MF, Kabesch M, Liang L, et al. Genetic variants regulating ORMDL3 expression

contribute to the risk of childhood asthma. Nature 2007;448:470-3.

9. Galanter J, Choudhry S, Eng C, et al. ORMDL3 gene is associated with asthma in three

ethnically diverse populations. Am J RespirCrit Care Med 2008:177:1194-1200.

10. Tavendale R, Macgregor DF, Mukhopadhay, et al. A polymorphism controlling ORMDL3

expression is associated with asthma that is poorly controlled by current medications. J

Allergy ClinImmunol 2008;121:860-3.

11. Wright RJ, Finn P, Contreras JP, et al. Chronic caregiver stress and IgE expression,

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Allergy ClinImmunol 2004;113:1051-7.

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12. Lin YC, Wen HJ, Lee YL, et al. Are maternal psychological factors associated with cord

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13. National Asthma Education and Prevention Program, Third Expert Panel on the

Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis

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Yth, dr. suweino Ini kumpulan makalah azmi, ayunda afdal, bathin bonia, brili, dan

Christopher.

Kira2 kapan sebaiknya kami mempresentasikan inggris 3 ini ??

Ing3 Completed

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