Diabetes Kuliah 1

7/26/2019 Diabetes Kuliah 1

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Prof. Dr Syed-Azhar Syed Sulaiman

School of Pharmaceutical Sciences

Universiti sains Malaysia


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Diabetes mellitus (DM) is a grou of diseasescharacterized by high levels of blood glucoseresulting from defects in insulin roduction! insulinaction! or both.

"he term diabetes mellitus describes a metabolicdisorder of multile aetiology characterized bychronic hyerglycaemia #ith disturbances ofcarbohydrate! fat and rotein metabolism resultingfrom defects in insulin secretion! insulin action! or

both.

"he e$ects of diabetes mellitus include long%termdamage! dysfunction and failure of various organs.


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Diabetes mellitus may resent #ith characteristicsymtoms such as thirst! olyuria! blurring of vision!and #eight loss.

&n its most severe forms! 'etoacidosis or a non%'etotic hyerosmolar state may develo and lead tostuor! coma and! in absence of e$ective treatment!death.

ften symtoms are not severe! or may be absent!and conseuently hyerglycaemia su*cient to causeathological and functional changes may be resentfor a long time before the diagnosis is made.


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"he long%term e$ects of diabetes mellitusinclude rogressive develoment of the seci+ccomlications of retinoathy #ith otentialblindness! nehroathy that may lead to renal

failure! and,or neuroathy #ith ris' of footulcers! amutation! harcot oints! and featuresof autonomic dysfunction! including se/ualdysfunction.

Peole #ith diabetes are at increased ris' ofcardiovascular! eriheral vascular andcerebrovascular disease.


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"he develoment of diabetes is roected to reachandemic roortions over the ne/t01-21 years.

&nternational Diabetes 3ederation (&D3) dataindicate that by the year 2124! the number of

eole a$ected #ill reach 555 million %617 of theseeole #ill have "ye 2 diabetes.

&n most 8estern societies! the overall revalencehas reached 9-:7! and is as high as 01-027 among:1-;1-year-old eole.

"he annual health costs caused by diabetes and itscomlications account for around :-027 of allhealth-care e/enditure.


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"ye 0 Diabetes Mellitus"ye 2 Diabetes MellitusADA (

MD? (maturity-onset diabetes ofyouth)

Secondary Diabetes Mellitus


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Was previously called insulin-dependent diabetesmellitus (IDDM) or juvenile-onset diabetes.

Type 1 diabetes develops when the bodysimmune system destroys pancreatic beta cells!the only cells in the body that ma"e the hormone

insulin that re#ulates blood #lucose. This $orm o$ diabetes usually stri"es children and

youn# adults! althou#h disease onset can occur atany a#e.

Type 1 diabetes may account $or %& to 1'& o$ alldia#nosed cases o$ diabetes.

is" $actors $or type 1 diabetes may includeautoimmune! #enetic! and environmental $actors.


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Was previously called non-insulin-dependent diabetesmellitus (IDDM) or adult-onset diabetes.

Type * diabetes may account $or about +'& to +%& o$ alldia#nosed cases o$ diabetes.

It usually be#ins as insulin resistance! a disorder inwhich the cells do not use insulin properly. ,s the need$or insulin rises! the pancreas #radually loses its abilityto produce insulin.

Type * diabetes is associated with older a#e! obesity!$amily history o$ diabetes! history o$ #estationaldiabetes! impaired #lucose metabolism! physicalinactivity! and raceethnicity.

,$rican ,mericans! ispanic/atino ,mericans! ,mericanIndians! and some ,sian ,mericans and ativeawaiians or 0ther aci2c Islanders are at particularlyhi#h ris" $or type * diabetes.

Type * diabetes is increasin#ly bein# dia#nosed inchildren and adolescents.


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, $orm o$ #lucose intolerance that is dia#nosed insome women durin# pre#nancy.

3estational diabetes occurs more $re4uentlyamon# ,$rican ,mericans! ispanic/atino,mericans! and ,merican Indians. It is also more

common amon# obese women and women with a$amily history o$ diabetes.

Durin# pre#nancy! #estational diabetes re4uirestreatment to normali5e maternal blood #lucoselevels to avoid complications in the in$ant.

,$ter pre#nancy! %& to 1'& o$ women with#estational diabetes are $ound to have type *diabetes.

Women who have had #estational diabetes have a*'& to %'& chance o$ developin# diabetes in thene6t %-1' years.


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0ther speci2c types o$ diabetes result$rom speci2c #enetic conditions (suchas maturity-onset diabetes o$ youth)!sur#ery! dru#s! malnutrition!

in$ections! and other illnesses.

7uch types o$ diabetes may account $or

1& to %& o$ all dia#nosed cases o$diabetes.


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>atent Autoimmune Diabetes in Adults (>ADA)is a form of autoimmune(type 1 diabetes)#hich is diagnosed in individuals #ho are olderthan the usual age of onset of tye 0 diabetes.

Alternate terms that have been used for @>ADA@include >ate-onset Autoimmune Diabetes ofAdulthood! @Slo# nset "ye 0@ diabetes! andsometimes also @"ye 0.4

ften! atients #ith >ADA are mista'enlythought to have type 2 diabetes! based ontheir age at the time of diagnosis.


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About 17 of adults aarently #ithrecently diagnosed "ye 2 diabetes but #ithADA) rogress toinsulin reuirement #ithin : years.

"he otential value of identifying this grouat high ris' of rogression to insulindeendence includes=

the avoidance of using metformin treatment

the early introduction of insulin theray


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MD? % Maturity nset Diabetes of the ?oung

MD? is a monogenic form of diabetes #ith anautosomal dominant mode of inheritance= Mutations in any one of several transcrition factors or in the

enzyme gluco'inase lead to insu*cient insulin release from

ancreatic B-cells! causing MD?. Di$erent subtyes of MD? are identi+ed based on the mutated

gene.

riginally! diagnosis of MD? #as based on resence ofnon-'etotic hyerglycemia in adolescents or young

adults in conunction #ith a family history of diabetes.

Co#ever! genetic testing has sho#n that MD? canoccur at any age and that a family history of diabetes isnot al#ays obvious.


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8ithin MD?! the di$erent subtyes canessentially be divided into 2 distinct grous=gluco'inase MD? and transcrition factorMD?! distinguished by characteristichenotyic features and attern on oral glucose

tolerance testing.


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Secondary causes of Diabetes mellitus include=

Acromegaly! ushing syndrome! "hyroto/icosis! Pheochromocytoma hronic ancreatitis! ancer

Drug induced hyerglycemia= Atyical Antisychotics - Alter recetor binding characteristics! leading to

increased insulin resistance.

Feta-bloc'ers - &nhibit insulin secretion.

alcium hannel Floc'ers - &nhibits secretion of insulin by interfering #ithcytosolic calcium release.

orticosteroids - ause eriheral insulin resistance and gluconeogensis.

3luorouinolones - &nhibits insulin secretion by bloc'ing A"P sensitive otassium

channels. aicin - "hey cause increased insulin resistance due to increased free fatty acid

mobilization.

Phenothiazines - &nhibit insulin secretion.

Protease &nhibitors - &nhibit the conversion of roinsulin to insulin.

"hiazide Diuretics - &nhibit insulin secretion due to hyo'alemia. "hey also causeincreased insulin resistance due to increased free fatty acid mobilization.


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Prediabetes is a term used to distinguish eole#ho are at increased ris' of develoing diabetes.Peole #ith rediabetes have imaired fastingglucose (&3


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Progression to diabetes among those #ithrediabetes is not inevitable. Studies suggestthat #eight loss and increased hysical activityamong eole #ith rediabetes revent or delaydiabetes and may return blood glucose levels tonormal.

Peole #ith rediabetes are already at increased

ris' for other adverse health outcomes such asheart disease and stro'e.


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Gesearch studies have found that lifestyle changescan revent or delay the onset of tye 2 diabetesamong high-ris' adults.

"hese studies included eole #ith &


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Studies have sho#n that medications have been successful inreventing diabetes in some oulation grous.

&n the Diabetes Prevention Program! eole treated #ith thedrug metformin reduced their ris' of develoing diabetes by507 over 5 years.

"reatment #ith metformin #as most e$ective among younger!heavier eole (those 24-91 years of age #ho #ere 41 to 1ounds over#eight) and less e$ective among older eole andeole #ho #ere not as over#eight.

Similarly! in the S"P-&DDM "rial! treatment of eole #ith&


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Mana#ement o$

DiabetesMellitus


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"he maor comonents of the treatment ofdiabetes are=


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Diet is a basic art of management in everycase. "reatment cannot be e$ective unlessadeuate attention is given to ensuringaroriate nutrition.

Dietary treatment should aim at8 ensuring #eight control

roviding nutritional reuirements

allo#ing good glycaemic control #ith bloodglucose levels as close to normal as ossible

correcting any associated blood liidabnormalities


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The $ollowin# principles are recommended as dietary

#uidelines $or people with diabetes8

Dietary fat should rovide 25-35% of total intake of caloriesbut saturated fat intake should not e/ceed 017 of total energy.holesterol consumtion should be restricted and limited to511 mg or less daily.

Protein inta'e can range bet#een 01-047 total energy (1.-0g,'g of desirable body #eight). Geuirements increase forchildren and during regnancy. Protein should be derived fromboth animal and vegetable sources.

arbohydrates rovide 50-60% of total caloric content of the

diet. arbohydrates should be comle/ and high in +bre.

H/cessive salt inta'e is to be avoided. &t should be articularlyrestricted in eole #ith hyertension and those #ithnehroathy.


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Physical activity romotes #eight reduction andimroves insulin sensitivity! thus lo#ering bloodglucose levels.

"ogether #ith dietary treatment! a rogramme

of regular hysical activity and e/ercise shouldbe considered for each erson. Such arogramme must be tailored to the individualIshealth status and +tness.

Peole should! ho#ever! be educated about theotential ris' of hyoglycaemia and ho# toavoid it.


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"here are currently four classes of oral anti-diabetic agents=

i. Figuanides

ii. &nsulin Secretagogues % Sulhonylureas

iii. &nsulin Secretagogues % on-sulhonylureas

iv. J-glucosidase inhibitorsv. "hiazolidinediones ("KDs)


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&f glycaemic control is not achieved (CbA0c L:.47 and,or 3P< L ;.1 mmol,> or GP) #ith lifestyle modi+cation #ithin0 %5 months! GA> A"&-D&AFH"& A


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As +rst line theray=

bese tye 2 atients! consider use of metformin,acarbose or "KD.

on-obese tye 2 atients! consider the use ofmetformin or insulin secretagogues

Metformin is the drug of choice in over#eight,obeseatients. "KDs and acarbose are accetable alternativesin those #ho are intolerant to metformin.

&f monotheray fails! a combination of "KDs! acarboseand metformin is recommended. &f targets are still notachieved! insulin secretagogues may be added


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ombination oral agents is indicated in=

e#ly diagnosed symtomatic atients #ithCbA0c L01

Patients #ho are not reaching targets after5 months on monotheray


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&f targets have not been reached after otimal dose ofcombination theray for 5 months! consider addingintermediate-acting,long-acting insulin (F&DS).

ombination of insulinN oral anti-diabetic agents (F&DS) hasbeen sho#n to imrove glycaemic control in those notachieving target desite ma/imal combination oral anti-diabetic agents.

ombining insulin and the follo#ing oral anti-diabetic agentshas been sho#n to be e$ective in eole #ith tye 2 diabetes= Figuanide (metformin) &nsulin secretagogues (sulhonylureas)

&nsulin sensitizers ("KDs)(the combination of a TZD lus insulin is not anaroved indication) J-glucosidase inhibitor (acarbose)

&nsulin dose can be increased until target 3P< is achieved.


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DiabetesMana#ement

,l#orithm


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&n elderly non-obese atients! short acting insulin

secretagogues can be started but long acting Sulhonylureasare to be avoided. Genal function should be monitored.

ral anti-diabetic agent s are not recommended for diabetes inregnancy

ral anti-diabetic agents are usually not the +rst line therayin diabetes diagnosed during stress! such as infections. &nsulintheray is recommended for both the above

"argets for control are alicable for all age grous. Co#ever!in atients #ith co-morbidities! targets are individualized

8hen indicated! start #ith a minimal dose of oral anti-diabeticagent! #hile reemhasizing diet and hysical activity. Anaroriate duration of time (2-0: #ee's deending on agentsused) bet#een increments should be given to allo#achievement of steady state blood glucose control


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7hort-term use8 Acute illness! surgery! stress and emergencies Pregnancy Freast-feeding &nsulin may be used as initial theray in tye 2 diabetes in mar'ed hyerglycaemia Severe metabolic decomensation (diabetic 'etoacidosis!

hyerosmolar non'etotic coma! lactic acidosis! severehyertriglyceridaemia)

/on#-term use8 &f targets have not been reached after otimal dose of

combination theray or F&DS! consider change to multi-doseinsulin theray. 8hen initiating this!insulin secretagoguesshould be stoed and insulin sensitisers e.g. Metformin or"KDs! can be continued.


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"he maority of atients #ill reuire more than one dailyinection if good glycaemic control is to be achieved.

Co#ever! a once-daily inection of an intermediate actingrearation may be e9ectively used in some patients.

"#ice-daily mi/tures of short- and intermediate-acting insulinis a commonly used regimen.

In some cases! a mi6ture o$ short- and intermediate-actin# insulin may be #iven in the morning. 3urther dosesof short-acting insulin are given before lunch and the eveningmeal and an evening dose of intermediate-acting insulin isgiven at bedtime.

ther regimens based on the same rinciles may be used.

A regimen of multile inections of short-acting insulin beforethe main meals! #ith an aroriate dose of an intermediate-acting insulin given at bedtime! may be used! articularly#hen strict glycaemic control is mandatory.


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Patients should be educated to ractice self-care. "his allo#s the atient to assumeresonsibility and control of his , her o#ndiabetes management. Self-care shouldinclude=

Flood glucose monitoring Fody #eight monitoring 3oot-care Personal hygiene Cealthy lifestyle,diet or hysical activity &dentify targets for control Stoing smo'ing


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ational Diabetes :act 7heet *'';! D


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Diabetes Kuliah 1

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