Ad Pathology

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DIABETESDIABETESMELLITUSMELLITUSDIABETESDIABETESMELLITUSMELLITUS

Dr Prakash H MDr Prakash H MDr Prakash H MDr Prakash H M



What is diabetes mellitus?

The majority of intake of food isThe majority of intake of food isconverted into glucose.converted into glucose.

The pancreas produces the insulinThe pancreas produces the insulinhormone, which help the organism tohormone, which help the organism totake advantage of glucose.take advantage of glucose.

In persons with diabetes, the insulin doesIn persons with diabetes, the insulin doesnot work. Therefore, the sugar and thenot work. Therefore, the sugar and thefat increase in the blood.fat increase in the blood.



T he World Wide Epidemic:Prevalenceof Diabetes

5%

8%

14%

4%

3%



T he Worldwide Epidemic:Diabetes Trends

30

135177

221

300

370

0

50

100

150

200

250

300

350

400

i i n s

i t D

i a b e

t e s

1985 1995 2000 2010 2025 2030

Sources: www.who.int www.idf

Zimmet P. et al Nature: 414, 13 Dec 2001



PHYSIOLOGICAL IMPACT66 thth leading cause of death by diseaseleading cause of death by diseaseDecreases life expectancy of middleDecreases life expectancy of middle--aged peopleaged people by 5 by 5--10 years10 years

22--4 x greater risk of death d/t heart disease4 x greater risk of death d/t heart disease ± ± Compounding factors include: duration of disease,Compounding factors include: duration of disease,glycemic control, HTN , smoking, dyslipidemia,glycemic control, HTN , smoking, dyslipidemia,decreased activity, and obesitydecreased activity, and obesity

Leading cause of blindness in 25Leading cause of blindness in 25--74 year olds74 year oldsLeading cause of nonLeading cause of non--traumatic amputationstraumatic amputationsResponsible for 25Responsible for 25--30% of all new dialysis30% of all new dialysis patients patients



DIABET ES MELLITU SDefinition: a metabolic disorder in whichDefinition: a metabolic disorder in which

there is deficiency of insulinthere is deficiency of insulin production or resistance of organs to production or resistance of organs tothe effect of insulinthe effect of insulin





DIABET ES MELLITU S After digestion, glucose passes into the After digestion, glucose passes into thebloodstream, where it is used by cells for bloodstream, where it is used by cells for growth and energy.growth and energy.For glucose to get into cells, insulin must beFor glucose to get into cells, insulin must bepresent.present.Insulin is a hormone produced by theInsulin is a hormone produced by the

pancreas, a large gland behind the stomach.pancreas, a large gland behind the stomach.

<http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what><http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what>



Regu l ti f Bl S uga r

High blood sugar High blood sugar I suli

Pancreas Glycogen G luc s e

De cr ea s ed

Glycogen

synthase

IncreasedIncreased

Hormone

Signal TransductionSignal Transduction

Bl dLive r Live r

Low blood sugar Glucagon

GTP-protein-linked receptor

Tyrosine-kinase-linked receptor

Glycogen phosphorylase

Co ri & Co ri (1947)

J uang RH (2004) B Cb a sics







Normal glucose homeostasis is tightly

regulated by three interrelated processes:

(1) glucose production in the liver,(1) glucose production in the liver,(2) glucose uptake and utilization by(2) glucose uptake and utilization by peripheral tissues, chiefly skeletal muscle, peripheral tissues, chiefly skeletal muscle,

(3) actions of insulin and counter (3) actions of insulin and counter--regulatory hormones(e.g., glucagon).regulatory hormones(e.g., glucagon).



DIABET ES MELLITU SNOR M A : When nonNOR M A : When non- -diabetic people eat, thediabetic people eat, thepancreas automatically produces the rightpancreas automatically produces the right

amount of insulin to mo e glucose from bloodamount of insulin to mo e glucose from bloodinto our cells.into our cells.




DIABET ES MELLITU SDI ABETES: In people with diabetes, whenDI ABETES: In people with diabetes, whenthey eat, the pancreas either produces littlethey eat, the pancreas either produces littleor no insulin, or the cells do not respondor no insulin, or the cells do not respondappropriately to the insulin that is producedappropriately to the insulin that is produced(or both) => glucose builds up in the blood,(or both) => glucose builds up in the blood,o erflows into the urine, and passes out of o erflows into the urine, and passes out of the body in urine => body loses its mainthe body in urine => body loses its mainsource of fuel e en though blood containssource of fuel e en though blood containslarge amounts of glucose.large amounts of glucose.<http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what><http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what>



Diabetes mellitus is not a single diseaseDiabetes mellitus is not a single diseaseentity but rather aentity but rather a group of metabolic group of metabolicdisorders sharing the common underlying disorders sharing the common underlying

feature of hyperglycemia. feature of hyperglycemia.



Hyperglycemia in diabetes

results fromdefects in insulin secretion,defects in insulin secretion,defects in insulin action,defects in insulin action,most commonly, both.most commonly, both.



T he principal metabolic function of insulinT he principal metabolic function of insulin

is to increase the rate of glucose transport is to increase the rate of glucose transport into certain cells in the bodyinto certain cells in the bodyT hese are theT hese are the striated muscle cells striated muscle cells(including myocardial cells) and, to a lesser(including myocardial cells) and, to a lesserextent,extent,adipocytes,adipocytes, representing collectivelyrepresenting collectivelyabout twoabout two--thirds of the entire body weight.thirds of the entire body weight.Glucose uptake in other peripheral tissues,Glucose uptake in other peripheral tissues,most notably the brain, is insulinmost notably the brain, is insulinindependent.independent.



metabolic effects of insulinmetabolic effects of insulin - - anabolic, withanabolic, withincreased synthesis and reduced increased synthesis and reduced degradation of glycogen, lipid, and protein.degradation of glycogen, lipid, and protein.In additionIn addition -- severalseveralmitogenicmitogenic functions,functions,including initiation of D N A synthesis inincluding initiation of D N A synthesis incertain cells and stimulation of their growthcertain cells and stimulation of their growthand differentiation.and differentiation.





Etiologic Classification of

Diabetes MellitusType DiabetesType Diabetes -- --cell destruction, leads to absolutecell destruction, leads to absoluteinsulin deficiencyinsulin deficiencyType DiabetesType Diabetes --Insulin resistance with relative insulinInsulin resistance with relative insulindeficiencydeficiencyG enetic Defects of G enetic Defects of --Cell FunctionCell FunctionG enetic Defects in Insulin Processing or Insulin ActionG enetic Defects in Insulin Processing or Insulin ActionExocrine Pancreatic DefectsExocrine Pancreatic DefectsEndocrinopathiesEndocrinopathies

InfectionsInfectionsDrugsDrugsG enetic Syndromes Associated with DiabetesG enetic Syndromes Associated with DiabetesG estational Diabetes MellitusG estational Diabetes Mellitus



DMT YPE IAutoAuto--immune diseaseimmune diseaseConstitutesConstitutes - - % of DM diagnosed in the% of DM diagnosed in the

USAUSAMostly appears in children and young adultsMostly appears in children and young adultsDevelops as a result of autoDevelops as a result of auto- -immuneimmune

destruction of betadestruction of beta- -cells in the pancreascells in the pancreasPresents with polyuria, thirst, weight loss,Presents with polyuria, thirst, weight loss,

marked fatiguemarked fatigueCan be complicated by coma with ketoacidosisCan be complicated by coma with ketoacidosis




DMT YPE IIMost common form of diabetesMost common form of diabetesInvolves aboutInvolves about - - % of people with DM% of people with DMAssociated with:Associated with:

± ± older ageolder age ± ± obesityobesity ± ± family history of DMfamily history of DM

± ± prior history of gestational diabetesprior history of gestational diabetes ± ± physical inactivityphysical inactivity ± ± ethnicityethnicity




DMT YPE IIPatient with type II DM usually makesPatient with type II DM usually makesenough insulin but the body cannot use itenough insulin but the body cannot use iteffectively =>effectively =>insulin resistanceinsulin resistanceGraduallyGraduallyinsulin productioninsulin production decreases over decreases over the following yearsthe following years

Symptoms are similar to type I but developSymptoms are similar to type I but developmore graduallymore gradually




G enetic defects of -cell

functionMaturity-onset diabetes of the young(MODY),

caused by mutations in:Hepatocyte nuclear factor 4( H NF4A ), MODY1Glucokinase(GCK ), MODY2Hepatocyte nuclear factor 1( H NF1A ), MODY3Pancreatic and duodenal homeobox 1( PDX1 ), MODY4Hepatocyte nuclear factor 1( H NF1B ), MODY5N eurogenic differentiation factor 1( NEUROD1 ), MODY6

N eonatal diabetes(activating mutations in KC NJ11 and ABCC8 ,

encoding Kir 6 .2 and SU R1, respectively) Maternally inheriteddiabetes and deafness(MIDD) due to mitochondrial D N A mutations(m.3243A G) Defects in proinsulin conversion Insulin genemutations



Maturity onset Diabetes of

Young {MODY }Insulin secretory defect without beta cellInsulin secretory defect without beta celllossloss

Autosomal dominant inheritance with highAutosomal dominant inheritance with high penetrance penetranceEarly onset before 25Early onset before 25

ImpairedImpaired -- cell function , normal weight ,cell function , normal weight ,lack of GAD antibodies ,lack of GAD antibodies ,lack of I N SU LI N resistance syndromelack of I N SU LI N resistance syndrome



G enetic defects in insulin

actionT ype A insulin resistanceLipoatrophic diabetes, including mutationsin PPAR G



Exocrine pancreatic defects

Chronic pancreatitisPancreatectomy/trauma N eoplasiaCystic fibrosisHemachromatosisFibrocalculous pancreatopathy



Endocrinopathies

AcromegalyCushing syndromeHyperthyroidismPheochromocytomaGlucagonoma



Infections

CytomegalovirusCoxsackie B virusCongenital rubella



Drugs

GlucocorticoidsT hyroid hormone

Interferon-Protease inhibitors

-adrenergic agonists

T hiazides N icotinic acidPhenytoin(Dilantin) Vacor



G enetic syndromes

associated with diabetesDown syndromeKleinfelter syndromeT urner syndromePrader-Willi syndrome



GEST AT IO N AL DIABET ESDevelops only during pregnancyDevelops only during pregnancyMore common in:More common in: ± ± African AmericansAfrican Americans ± ± American IndiansAmerican Indians ± ± Hispanic AmericansHispanic Americans

± ± women with a family history of diabeteswomen with a family history of diabetesWomen with a history of gestational diabetes haveWomen with a history of gestational diabetes havea 20a 20--50% chance of getting type II DM within 550% chance of getting type II DM within 5--10 years10 years <http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what><http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#what>



Gestational Diabetes MellitusHyperglycemia diagnosed during pregnancyHyperglycemia diagnosed during pregnancyOccurs in 2Occurs in 2--5% of pregnancies5% of pregnanciesOccurs due to placental hormone changes thatOccurs due to placental hormone changes thateffect insulin function(greater resistance)effect insulin function(greater resistance)

Screening usually occurs during the 24Screening usually occurs during the 24thth

--2828thth

week week in high risk patientsin high risk patientsCriteria for diagnosis is different than for T ype 1Criteria for diagnosis is different than for T ype 1andT ype 2andT ype 2

Dietary changes are initial treatment and insulin isDietary changes are initial treatment and insulin isthe only BG lowering agent usedthe only BG lowering agent usedConcern is both for maternal and fetal wellConcern is both for maternal and fetal well--being beingPostpartum BG levels usually return to normalPostpartum BG levels usually return to normal

Increased risk for T ype 2 diabetes(30Increased risk for T ype 2 diabetes(30--50%)50%)



Pathogenesis of T ype 1

Diabetes Mellitusautoimmune diseaseautoimmune disease in which islet destruction is causedin which islet destruction is caused primarily byT lymphocytes reacting against as yet poorly primarily byT lymphocytes reacting against as yet poorlydefineddefined --cell antigens, resulting in a reduction incell antigens, resulting in a reduction in --cellcellmassmassgenetic susceptibility and environmental influences playgenetic susceptibility and environmental influences playimportant roles in the pathogenesis.important roles in the pathogenesis.most commonly develops in childhood, becomes manifestmost commonly develops in childhood, becomes manifestat puberty, and is progressive with age.at puberty, and is progressive with age.Most individuals with type 1 diabetes depend onMost individuals with type 1 diabetes depend onexogenous insulin supplementation for survival, andexogenous insulin supplementation for survival, andwithout insulin, they develop serious metabolicwithout insulin, they develop serious metabolic

complications such as acute ketoacidosis and coma.complications such as acute ketoacidosis and coma.



T he classic manifestations of the diseaseT he classic manifestations of the disease(hyperglycemia and ketosis) occur late in its(hyperglycemia and ketosis) occur late in itscourse, after more than 90% of thecourse, after more than 90% of the cellscellshave been destroyed.have been destroyed.Several mechanisms contribute toSeveral mechanisms contribute to --cell cell

destruction, and it is likely that many of destruction, and it is likely that many of these immune mechanisms work together tothese immune mechanisms work together to

produce progressive loss of produce progressive loss of cells,cells,resulting in clinical diabetes:resulting in clinical diabetes:





T ype 1 diabetescomplex pattern of genetic associationcomplex pattern of genetic associationthe principal susceptibility locus for type 1 diabetes residesthe principal susceptibility locus for type 1 diabetes residesin the region that encodes the class II M HC molecules onin the region that encodes the class II M HC molecules onchromosome 6p21 ( HL Achromosome 6p21 ( HL A--D) D) ..Between 90% and 95%Between 90% and 95% -- HL A HL A--DR3 DR3 , or , or DR4 DR4 , or both,, or both,also evidence to suggest thatalso evidence to suggest thatenvironmental factorsenvironmental factors ,,especially infections,especially infections, -- viruses may be an initiating trigger,viruses may be an initiating trigger,--molecular minicrymolecular minicry



Pathogenesis of T ype 2

Diabetes Mellitus pathogenesis of type 2 diabetes remains enigmatic. pathogenesis of type 2 diabetes remains enigmatic.Environmental influences, such as a sedentary lifeEnvironmental influences, such as a sedentary life

style and dietary habits, clearly have a role,style and dietary habits, clearly have a role, N evertheless, N evertheless, genetic factors are even more genetic factors are even moreimportant than in type 1 diabetes,important than in type 1 diabetes,Among identical twins, the concordance rate isAmong identical twins, the concordance rate is50% to 90%, while among first50% to 90%, while among first--degree relativesdegree relativeswith type 2 diabetes(including fraternal twins) thewith type 2 diabetes(including fraternal twins) therisk of developing the disease is 20% to 40%risk of developing the disease is 20% to 40%



Insulin ResistanceInsulin resistance is defined as the failure of target tissues to respond normally to insulin.leads to decreased uptake of glucose inmuscle, reduced glycolysis and fatty acidoxidation in the liver, and an inability tosuppress hepatic gluconeogenesis.

Few factors play as important a role in the

development of insulin resistance asobesity .



Obesity and Insulin Resistance.epidemiologic association of obesity with type 2diabetes - observed in greater than 80% of patients.Insulin resistance is present even in simple obesityunaccompanied by hyperglycemia, indicating afundamental abnormality of insulin signaling in

states of fatty excess(see metabolic syndrome, below).

T he risk for diabetes increases as the body massindex(a measure of body fat content) increases. Itis not only the absolute amount but also thedistribution of body fat that has an effect oninsulin sensitivity:central obesity(abdominal fat) is more likely to

be linked with insulin resistance than are peripheral(gluteal/subcutaneous) fat depots.



Obesity can adversely impact insulin sensitivity in numerous ways Nonesterified fatty acids (NEFAs) : Adipokines: Leptin and adiponectin improve insulin sensitivity bydirectly enhancing the activity of the AMP-activated protein kinase(AMPK), an enzyme that promotes fatty acid oxidation, in liver andskeletal muscle. Adiponectin levels are reduced in obesity, thuscontributing to insulin resistance.

Inflammation: Adipose tissue also secretes a variety of pro-inflammatory cytokines like tumor necrosis factor, interleukin-6 , andmacrophage chemoattractant protein-1, the last attracting macrophagesto fat deposits.T hese cytokines induce insulin resistance by increasingcellular ³stress,´ which in turn, activates multiple signaling cascadesthat antagonize insulin action on peripheral tissues.

Peroxisome proliferator-activated receptor (PPAR ): PPAR is anuclear receptor and transcription factor expressed in adipose tissue,and plays a seminal role in adipocyte differentiation. Activation of PPAR promotes secretion of anti-hyperglycemic adipokines likeadiponectin, and shifts the deposition of N EFAs toward adipose tissueand away from liver and skeletal muscle. AS DISCU SSED BELOW,RARE MUT AT IO N S OF PPAR G T HAT CAU SE PROFOUN DLOSS OF PROT EI N FUN CT IO N CA N RESU LT I N MO N OGE N ICDIABET ES.



-Cell DysfunctionIn type 2 diabetes, cells seemingly exhaust their

capacity to adapt to the long-term demands of peripheral insulin resistance.In states of insulin resistance like obesity, insulinsecretion is initially higher for each level of glucose than in controls.T his hyperinsulinemicstate is a compensation for peripheral resistanceand can often maintain normal plasma glucose for years. Eventually, however, -cell compensation becomes inadequate, and there is progression tohyperglycemia.









T 2DM is a disorder characterized by aC ombination of reduced tissue sensitivity to

insulin and inadequate secretion of insulin from the pancreas.Hyperglycemia inT 2DM is a failure of theÎ²

cells to meet an increased demand for insulin in the body



MORP H O LOGY -

PAN C REAS TYPETYPE - -

-- reduction in number & size of isletsreduction in number & size of islets-- leukocytic infilteration of isletsleukocytic infilteration of islets

TYPETYPE - -

-- subtle reduction in islet cell masssubtle reduction in islet cell mass-- amyloid replacement of isletsamyloid replacement of islets













Diabetes MellitusAbsence(or ineffectiveness of ) insulinAbsence(or ineffectiveness of ) insulinCellular resistanceCellular resistanceCells can¶t use glucose for energyCells can¶t use glucose for energy ± ± Starvation modeStarvation mode

Compensatory breakdown of body fat/proteinCompensatory breakdown of body fat/protein

Ketone bodies from faulty fat breakdownKetone bodies from faulty fat breakdownMetabolic acidosis, compensatory breathingMetabolic acidosis, compensatory breathing(Kussmal¶s breathing)(Kussmal¶s breathing)













Type II Diabetes

Diagnostic testingDiagnostic testing -- when to do it:when to do it:

PeoplePeopleuu 45 years old45 years old => if normal then every=> if normal then every3 years3 years

MKSAP13 Endocrinology and Metabolism. American College of Physicians 2004.MKSAP13 Endocrinology and Metabolism. American College of Physicians 2004.



T ype II Diabetes: diagnostic testingYounger than 45 yr or more often than every 3 years if:Younger than 45 yr or more often than every 3 years if:

overweightoverweightfirst degree relative with diabetesfirst degree relative with diabetesmember of high risk ethnic group(Afromember of high risk ethnic group(Afro--American, HispanicAmerican, HispanicAmerican, N ative American, Asian American, Pacific Islander)American, N ative American, Asian American, Pacific Islander)

delivered a babydelivered a babyuu 9 lbs.9 lbs.gestational diabetesgestational diabeteshypertensive(BPhypertensive(BP uu 140/90mmHg)140/90mmHg)High Density Lipoprotein cholesterol 35mg/dl or lessHigh Density Lipoprotein cholesterol 35mg/dl or lessT riGlyceride level 250mg/dl or moreT riGlyceride level 250mg/dl or more

pre pre--diabetesdiabetesMKSAP13 Endocrinology and Metabolism. American College of Physicians 2004.MKSAP13 Endocrinology and Metabolism. American College of Physicians 2004.



Who·s at risk of Type II?Who·s at risk of Type II?



Diabetes MellitusT he good news:T he good news:

± ± Blood glucose control reduces complications of Blood glucose control reduces complications of Diabetes!Diabetes!



Diabetes MellitusComplications of chronic hyperglycemiaComplications of chronic hyperglycemia ± ± Macrovascular Macrovascular complicationscomplications

Cardiovascular disease(heart attack)Cardiovascular disease(heart attack)Cerebrovascular disease(strokes)Cerebrovascular disease(strokes)

± ± Microvascular Microvascular Blindness(retinal proliferation, macular degeneration)Blindness(retinal proliferation, macular degeneration)

AmputationsAmputationsDiabetic neuropathy(diffuse, generalized, or focal)Diabetic neuropathy(diffuse, generalized, or focal)Erectile dysfunctionErectile dysfunction





The Laboratory Examination

Laboratory plays an importantLaboratory plays an important part in the diagnosis and care of part in the diagnosis and care ofdiabetic patientsdiabetic patients



DiagnosisBlood glucose levelsBlood glucose levels -- 70 to 120 mg/dL.70 to 120 mg/dL.DiagnosisDiagnosis -- By Elevation Of Blood Glucose ByBy Elevation Of Blood Glucose ByAny One Of T hree Criteria:Any One Of T hree Criteria:A random blood glucose concentration of 200A random blood glucose concentration of 200

mg/dL or higher, with classical signs andmg/dL or higher, with classical signs andsymptomssymptomsA fasting glucose concentration of 126 mg/dL or A fasting glucose concentration of 126 mg/dL or higher on more than one occasion,higher on more than one occasion,

An abnormal oral glucose tolerance test(OGTT ),An abnormal oral glucose tolerance test(OGTT ),in which the glucose concentration is 200 mg/dLin which the glucose concentration is 200 mg/dLor higher 2 hours after a standard carbohydrateor higher 2 hours after a standard carbohydrateload(75 gm of glucose).load(75 gm of glucose).





Reference IntervalFasting glucose : 3.9Fasting glucose : 3.9 -- 6 .11mmol/l6 .11mmol/l

(fasting is defined as no calorieintake for at least 8 hours)



Urine

Tests

U RI N E "GLU COSEU RI N E "GLU COSE"" ± ± lacks sensitivity = positivity in diseaselacks sensitivity = positivity in disease

± ± poor specificity = negativity in poor specificity = negativity inhealthhealthProblemsProblems ± ± renal threshold variable6 to 15 mmol/Lrenal threshold variable6 to 15 mmol/L ± ± interferences : Clinitest / Glucose oxidase stripsinterferences : Clinitest / Glucose oxidase strips

IF U RI N E T EST POSIT IVEIF U RI N E T EST POSIT IVEA CO N FIRMAT ORY BLOODT ESTA CO N FIRMAT ORY BLOODT EST

IS N EEDEDIS N EEDED



BloodT

estsGlucoseGlucose ± ± whole blood 10whole blood 10--15% lower than plasma15% lower than plasma

± ± venous 10% lower than capillaryvenous 10% lower than capillary ± ± Venous bloodVenous blood -- loss of 0.33 mmol/L per loss of 0.33 mmol/L per hour hour

± ± T

here is no decrease within 24 h in theT

here is no decrease within 24 h in the presence of sodium fluoride presence of sodium fluoride



Oral GlucoseT oleranceT est(OGTT )

A venous blood sample will be collected forA venous blood sample will be collected forthe determination of fasting glucosethe determination of fasting glucoseLoad of 75g of glucose is ingested within 5Load of 75g of glucose is ingested within 5minminBlood samples will be collected at timedBlood samples will be collected at timedintervals(30min,6 0min, 120min) for theintervals(30min,6 0min, 120min) for thedetermination of glucosedetermination of glucose





OGTT

CriteriaPlasma glucose (mmol/L)Plasma glucose (mmol/L)

min minmin min

Non diabeticNon diabetic < 6.< 6. < .< .

Impaired glucose tolerance 6.Impaired glucose tolerance 6. - - 6.6. > .> . --

..

DiabeticDiabetic > .> . > .> .



Glycosylated proteinsCaused by nonCaused by non--enzymatic glycosylationenzymatic glycosylation ± ± Glycosylated hemoglobinGlycosylated hemoglobin

HbAHbA1c1c -- LGI ref range 4.6LGI ref range 4.6 --6 .5 %6 .5 %

indicates previous 2indicates previous 2--3 months glycaemic exposure3 months glycaemic exposuren.b. affetced by altered red cell survivaln.b. affetced by altered red cell survival ± ± FructosamineFructosamine

mirrors glycosylation of all serum proteinsmirrors glycosylation of all serum proteinsindicates previous 2indicates previous 2--3 weeks glycaemic exposure3 weeks glycaemic exposureused pregnancy/children in some sitesused pregnancy/children in some sites

± ± Glycosylated albuminGlycosylated albuminindicates previous several days glycaemic exposureindicates previous several days glycaemic exposurenot commonly usednot commonly used



Hemoglobin A1cHbA1c is stable glycosylatedHbA1c is stable glycosylatedhemoglobinhemoglobinIts percentage concentration indicatesIts percentage concentration indicatescumulative glucose exposurecumulative glucose exposure



Hemoglobin A1c

A good indicator of blood glucose control.A good indicator of blood glucose control.Gives a % that indicates control over theGives a % that indicates control over the

preceding 2 preceding 2--3 months.3 months.Performed 2 times a year.Performed 2 times a year.A hemoglobin of 6 % indicates good controlA hemoglobin of 6 % indicates good controland level >8% indicates action is needed.and level >8% indicates action is needed.

Lowe ri HbA 1C Reduces Ri sk of Comp licat ions



Secondary Diabetes Mellitus

DM occurs as a result of another problemDM occurs as a result of another problem( primary)( primary) ± ± DiseasesDiseases ± ± ConditionsConditions

± ± MedicationsMedicationsT hiazidesT hiazidesDiureticsDiureticsBeta blockersBeta blockersSteroidsSteroids

Hyperglycemia is diagnostic for DMHyperglycemia is diagnostic for DMT reatment of the primary cause may resolve theT reatment of the primary cause may resolve theDM but lifestyle modifications and medicationsDM but lifestyle modifications and medicationsmay be needed as wellmay be needed as well



Pre-DiabetesPrePre--diabetes refers to a state betweendiabetes refers to a state between³normal´ and ³diabetes´ = fasting³normal´ and ³diabetes´ = fasting plasma glucose 100 plasma glucose 100--125mg/dL(higher 125mg/dL(higher than normal but not high enough for than normal but not high enough for diagnosis of diabetes)diagnosis of diabetes)

Affects about 41 million people inAffects about 41 million people inU SAU SA ( previously referred to as either impaired( previously referred to as either impairedfasting glucose or impaired glucose tolerance)fasting glucose or impaired glucose tolerance)





Impaired GlucoseT oleranceDefined as a plasma blood glucose of >/= to 140Defined as a plasma blood glucose of >/= to 140 but< 200 after a 2 hour 75 gram glucose tolerance but< 200 after a 2 hour 75 gram glucose tolerancetesttest88--10% of U S population have this problem with a10% of U S population have this problem with a25 % risk of developing DM 225 % risk of developing DM 2Compounding risk factors effect risk of Compounding risk factors effect risk of developingT ype 2 DMdevelopingT ype 2 DM ± ± AgeAge ± ± ActivityActivity ± ± ComorbiditiesComorbidities ± ± WeightWeightIncreased risk for macrovascular diseasesIncreased risk for macrovascular diseasesMust educate regarding risks and need for lifestyleMust educate regarding risks and need for lifestylemodificationsmodifications



Diabetes is preventable by life stylemodification

Maintain a healthy body weightMaintain a healthy body weight

Half an hour of exercise dailyHalf an hour of exercise dailyEat a healthy dietEat a healthy diet(fruits, egetables, bread, milk)



T

riad of T

reatmentDietDiet

MedicationMedication ± ± Oral hypoglycemicsOral hypoglycemics ± ± InsulinsInsulins

ExerciseExercise



Diabetes MellitusPrevention of effects: combination approachPrevention of effects: combination approach ± ± Increased exerciseIncreased exercise

Decreases need for insulinDecreases need for insulin

± ± Reduce calorie intakeReduce calorie intakeImproves insulin sensitivityImproves insulin sensitivity

± ± Weight reductionWeight reductionImproves insulin actionImproves insulin action

Cl ifi i f Di b



Class if icat ion of Dia b etesType I DMType I DM Type II DMType II DM

Aet io logy Autoimmune( F- cell destruction)

Insulin resistance and F-celldysfunction

P eak age 12 years 6 years

P r eva lence .3% 6% (> 10 % abo e 6 0 years)

P r esentat ion O smotic symptoms,weight loss (days toweeks), DK AP atient usually slim

O smotic symptoms, diabeticcomplications (months toyears).P atient usually obese

Tr eatment Diet and insulin Diet, exercise (weight loss),oral hypoglycemics, Insulin

later



Diabetes is a very complicated disease. It isDiabetes is a very complicated disease. It iseasy to diagnosis and it is difficult to treateasy to diagnosis and it is difficult to treat

Laboratory plays an important part in theLaboratory plays an important part in thediagnosis and care of diabetic patientsdiagnosis and care of diabetic patients

In Conclusion :

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Ad Pathology