complications of diabetes mellitus-update

8/9/2019 Complications of Diabetes Mellitus-update

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Complications ofComplications of

diabetes mellitusdiabetes mellitus


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Complications of DiabetesMellitus

ChronicComplications ofDiabetes Mellitus Microvascular

Retinopathy

(nonproliferative/proliferative) Nephropathy Neuropathy Sensory and motor (mono-

and polyneuropathy) Autonomic

Macrovascular Coronary artery disease eripheral vascular disease Cerebrovascular disease

AcuteComplications ofDiabetes Mellitus !yper"lycemia!yper"lycemia

crisiscrisis Diabetic

#etoacidosis !yper"lycemia

hyperosmolar State $actic acidosis

!ypo"lycemia


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MicrovascularMicrovascularComplicationsComplications


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Increased Polyol Pathway Flux Aldose Reductase Function


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AdvancedGlycation nd!Product

Formation

i i f i i


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Activation of Protein "inaseC


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Increased #exosamine Pathway


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Diabetic retinopathy Diabetic retinopathy


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Hyperglycemia

Pericyte

loss

Hyperperfusion Capillary/

Endothelial

damage

Loss of

autoregulation

Capillary

occlusion

Vasoactive

factorsLoss of tight

junction

Retinal

ischemia

New vessels -Low resistance

- No pericyte/autoregulation

rowth

factorsMacular

oedema

Pathophysiolo$y of diabeticPathophysiolo$y of diabetic

retinopathy retinopathy


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Advanced diabetic eye Advanced diabetic eye

diseasediseaseRetinal ischemia

Pericyte

loss

Neovascularitation

Preretinal

haemorrhage

Neovascularglaucoma Vitroushaemorrhage !etinaldetachment

Blindness


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Diabetic retinopathy Diabetic retinopathy

%lindness is primarily the result of pro"ressive diabeticretinopathy and clinically si"ni&cant macular edema'

Diabetic retinopathy is classi&ed into to sta"esnonproliferative and proliferative'

Nonproliferative diabetic retinopathy : mar#ed by retinal vascular microaneurysms* blot hemorrha"es* and cottonool spots

+he appearance of neovasculari,ation in response to retinalhypoia is the hallmar# of proliferative diabeticretinopathy '

Duration of DM and de"ree of "lycemic control are the bestpredictors of the development of retinopathy. hypertensionis also a ris# factor

+he most eective therapy for diabetic retinopathy isprevention'


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Diabetic nephropathy Diabetic nephropathy


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nephropathy nephropathy Hyperglycemia

Renal

vasodilatation Increased

intraglomerular

capillary pressure

Protein glycation

Increased glomular

filtration rateHypertension

Increased

protein excretion

Microalbuminuria or

macroalbuminuria

Nephropathy

Glomurular

damage


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Diabetic nephropathy Diabetic nephropathy is the leadin" cause of 0SRD in the 1S'

2ndividuals ith diabetic nephropathy almost alays have diabeticretinopathy' +he sta"es of diabetic nephropathy are :

Hyperltration Microalbuminuria Overtproteinuria Declining GFR End tage renal failure

Microalbuminuria is de&ned as 34 to 344 m"/d in a 56-h collection or34 to 344 "/m" creatinine in a spot collection (preferred method)'

+he appearance of microalbuminuria (incipient nephropathy) in type7 DM is an important predictor of pro"ression to overt proteinuria(344 m"/d) or overt nephropathy'

!ypertension more commonly accompanies microalbuminuria orovert nephropathy in type 5 DM


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Diabetic nephropathy !treatment

+he optimal therapy for diabetic nephropathy isprevention' 2nterventions eective in sloin" pro"ression from

microalbuminuria to overt nephropathy include near normali,ation of "lycemia* strict blood pressure control* and

administration of AC0 inhibitors or AR%s* and treatment of dyslipidemia'

%lood pressure should be maintained at 734/84 mm!"in diabetic individuals ithout proteinuria'

A sli"htly loer blood pressure (759/:9) should beconsidered for individuals ith microalbuminuria or

overt nephropathy A consensus panel of the ADA su""ests modest

restriction of protein inta#e in diabetic individuals ithmicroalbuminuria (4'8 "/#" per day) or overtnephropathy (;4'8 "/#" per day)


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Diabetic neuropathy Diabetic neuropathy

h i f d i


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Mechanism of nerve dama$e inMechanism of nerve dama$e in

diabetesdiabetes

METABOLI !A"#LAR

glucose

sor$itol

H%O

nerve

oedema

myoinositol

NO

production

A&E

'ormation

vasoconstriction

Arterial

narrowing

!essel

occlusion

"low nerve

conduction

Impairinga(onal transport

Altered mem$rane

potensial


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Diabetic neuropathy

Diabetic neuropathy occurs in approimately 94< ofindividuals ith lon"-standin" type 7 and type 5 DM'

+he development of neuropathy correlates ith theduration of diabetes and "lycemic control. bothmyelinated and unmyelinated nerve &bers are lost'

Several sta"e 2ntraneural biochemical abnormalities. sorbitol

accumulation* myoinositol depletion 2mpairement of electrophysiolo"ical measurement.

decreased nerve conduction velocity. asymptomatic Clinical neuropathy. detectable usin" clinical

methods. maybe symptomatic' !istolo"ical chan"esevident

0nd sta"e complications' 0p are ulceration andCharcot neuroarthropathy. ma=or deran"ements ofneural structure and function'

Cli i l f tCli i l f t


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Clinical featuresClinical features

symmetrical sensorimotorsymmetrical sensorimotor

neuropathy neuropathy SymptomsSymptoms $oss of sensation .$oss of sensation .

Anaesthesia.>numbness> Anaesthesia.>numbness>

$oss of pain perception$oss of pain perception Altered sensation Altered sensation

araesthesiaearaesthesiae DysaesthesiaeDysaesthesiae

ainain %urnin"%urnin" !yperal"esia/allodynia!yperal"esia/allodynia Neural"ia ? lancinatin" painNeural"ia ? lancinatin" pain Cramps . restless le"Cramps . restless le"

Si"nsSi"ns

Sensory lossSensory loss

Diminished/absentDiminished/absent

tendon re@estendon re@es Muscle astin" andMuscle astin" and

ea#nessea#ness

Autonomic Autonomic

dysfunctiondysfunction oot ulerationoot uleration


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Burning) 'eeling li*e the 'eet are on 'ire +ree,ing) li*e the 'eet are on ice)although they 'eel warm to touch

"ta$$ing) li*e sharp *nives Lancinating) li*e electric shoc*s


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%reatment of &ymmetric%reatment of &ymmetric

'europathy 'europathy Blucose controlBlucose control ain controlain control

+ricyclic antidepressants+ricyclic antidepressants Amitriptyline*desipramin* nortriptilin* Amitriptyline*desipramin* nortriptilin*

tra,odonetra,odone

Anticonvulsants Anticonvulsants

Carbama,epine* "abapentinCarbama,epine* "abapentin +opical creams+opical creams

capsaicincapsaicin

oot careoot care


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Autonomic 'europathy

DM-related autonomic neuropathy can involve multiplesystems* includin" the cardiovascular* "astrointestinal*"enitourinary* sudomotor* and metabolic systems'

Autonomic neuropathies aectin" the cardiovascularsystem cause a restin" tachycardia and orthostatichypotension'

Bastroparesis and bladderemptyin" abnormalities areoften caused by the autonomic neuropathy seen in DM(discussed belo)'

!yperhidrosis of the upper etremities and anhidrosis ofthe loer etremities result from sympathetic nervoussystem dysfunction'

Anhidrosis of the feet can promote dry s#in ith crac#in"*hich increases the ris# of foot ulcers' Autonomic neuropathy may reduce counterre"ulatory

hormone release* leadin" to an inability to sensehypo"lycemia appropriately ((hypoglycemia una!arene"


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MacrovascularMacrovascular

complicationscomplications


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MacrovascularMacrovascular

complicationcomplication Macrovascular complications of diabetes mellitus are

condition characteri,ed by atherosclerotic occlusivedisease of cerebral* myocard and loer etremities'

Atherothrombosis is the most common cause ofmacrovascular complications

Atherothrombosis is characteri,ed by a sudden(unpredictable) atherosclerotic plaue disruption(rupture or erosion) leadin" to platelet activation andthrombu formation

Atherothrombosis is the underlyin" condition thatresults in events leadin" to myocardial infarction*ischemic stro#e* amputation and vascular death

"th i " C l " d P i


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"therogenesis # " Comple$ "nd Progressive

Process%

Initiation-

Accumulation o' lipids atvascular .unctions

e(periencing high shear'orces

"dapted from& P Li''y( )he Vascular *iology of "therosclerosis( in& *raunwald

E( +ipes ,P Li''y P . th Edition( Heart Disease: a Textbook of Cardiovascular

Medicine 00%& London& 1* 2aunders3 3 ,avies 453 Heart 0006/0&7.%-..( with permission from the *45 Pu'lishing roup

Result- Atherosclerotic

pla1ue%

Macrophages

$ind to and enter

intima wallMacrophages

$ecome 'oam

cells 2 'atty

strea* 'ormed

"mooth muscle

cells 3"Ms4

migrate into the

intima

In'lammatory cyto*ines induce

e(pression o' adhesion molecules

#pta*e o' Lipids $y

Macrophages

hemo5attractants such as 67&+

released 'rom activated macrophages

6athology o' Atherogenesis


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"therothrom'osis Has 4ultiple

4anifestations

"dapted from& ,rouet L3 Cerebrovasc Dis 006808suppl %9&%#.

Transient ischemic attac*

Angina-: "ta$le: #nsta$le

Ischemic stro*e

Myocardial

in'arction

6eripheral arterial disease-: Intermittent claudication: Rest pain: &angrene: Necrosis


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Macrovascular disease inMacrovascular disease in

diabetes mellitusdiabetes mellitus Cardiovascular and cerebrovascular disease account for

up :4< of death in patients ith type 5 DM All patients ith type 5 diabetes have "reater

predipostition to macrovascular disease* often havin" aconstellation of ris# factors* hich have been term

inulin reitance' 2t has been hypotethesi,ed that insulin resistance and

hyperinsulinemia (environmental and "enetic factors)*are central to development Blucose intolerance !ypertension

Dyslipidemia Coa"ulopathy

+hese factors promote accelerated atherosclerosis*eplainin" the increased ris# of macrovascular disease'


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,ia'etes and 4acrovascular


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,ia'etes and 4acrovascular,isease

Li''y and Pluts;y3 Circulation. 003


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&trate$ies for reducin$&trate$ies for reducin$

macrovascular complicationsmacrovascular complications

revention proven intervention trialsrevention proven intervention trials !yper"lycemia!yper"lycemia

DyslipidemiaDyslipidemia !ypertension!ypertension Antiplatelet therapies Antiplatelet therapies

revention su""ested by epidemiolo"icrevention su""ested by epidemiolo"icanalysisanalysis Disorders of thrombolysisDisorders of thrombolysis 0ndothelial disorders0ndothelial disorders


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%he diabetic foot%he diabetic foot


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Diabetic foot diseaseDiabetic foot disease

Approimately 79< of individuals ith DM develop afoot ulcer* and a si"ni&cant subset ill ultimatelyunder"o amputation (76 to 56


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footfootNeuropathy

4otor

dysfunctionNeuropathy Neuropathy

"'normal


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Acute Complication of Acute Complication of

Diabetes MellitusDiabetes Mellitus

!yper"lycemia crisis!yper"lycemia crisisDiabetic #etoacidosis (DA)Diabetic #etoacidosis (DA)

!yper"lycemic !yperosmolar State (!!S) !ypo"lycemia!ypo"lycemia


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Diabetic (etoacidosisDiabetic (etoacidosis

)D"A*)D"A*#yper$lycemic

#yperosmolar &tate )##&*


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Pathophysiol$y ofPathophysiol$y of

hyper$lycemia crisishyper$lycemia crisis


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Diabetic (etoacidosis )D"A*Diabetic (etoacidosis )D"A*

DA as formerly considered a hallmar# oftype 7 DM

+he symptoms and physical si"ns of DA Symptoms Nausea/vomitin"* +hirst/polyuria* Abdominal pain* Shortness of breath

hysical &ndin"s +achycardia* Dry mucousmembranes/reduced s#in tur"or* Dehydration /hypotension* +achypnea / ussmaul*

respirations/respiratory distress* Abdominaltenderness (may resemble acute pancreatitis or sur"ical abdomen)* $ethar"y /obtundation /

cerebral edema / possibly coma


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Precipitatin$ factors

2nadeuate insulin administration

2nfection (pneumonia/1+2/

Bastroenteritis/sepsis 2nfarction (cerebral* coronary*

mesenteric* peripheral)

Dru"s (cocaine) re"nancy


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##&+ Di,erences from D"A ##&+ Di,erences from D"A

atients usually older- typically E4 or moreatients usually older- typically E4 or more Ma=or pathophysiolo"ic dierencesMa=or pathophysiolo"ic dierenceslon"er uncompensated osmotic diuresislon"er uncompensated osmotic diuresis"reater volume depletion"reater volume depletion

Acidemia (p! F :'3) and #etosis are mild Acidemia (p! F :'3) and #etosis are mild !i"her mortality -!i"her mortality -often 34-94


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De-nition of ##&De-nition of ##&

0treme hyper"lycemia0treme hyper"lycemia

2ncreased serum osmolality2ncreased serum osmolality

Severe dehydration ithoutSevere dehydration ithoutsi"ni&cant #etosis or acidosissi"ni&cant #etosis or acidosis

Joslin’s Diabetes Mellitus, 13th ed


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Clinical Findin$s of ##&Clinical Findin$s of ##&

!!S should be suspect elderly patient ith or ithout!!S should be suspect elderly patient ith or ithoutthe preeistin" dia"nosis of diabetes ho ehibits acutethe preeistin" dia"nosis of diabetes ho ehibits acute

or subacute deterioration of CNS function and severelyor subacute deterioration of CNS function and severely

dehydrateddehydrated

+achycardia+achycardia

$o "rade fever$o "rade fever $o or normal blood pressure$o or normal blood pressure

Dehydration ? dry mucous membrane* absent aillaryDehydration ? dry mucous membrane* absent aillary

seat* poor s#in tur"or'seat* poor s#in tur"or'

Nausea* vomitin"* distension* and pain-"astroparesis isNausea* vomitin"* distension* and pain-"astroparesis isdue to hypertonicitydue to hypertonicity

$ethar"y* hallucinations* and psychosis$ethar"y* hallucinations* and psychosis


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.aboratory Findin$s.aboratory Findin$s

D"A ##&

Fl id / l i Di b i


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Fluid /alance in DiabeticFluid /alance in Diabetic

#yperosmolarity #yperosmolarity ECF = 14 L ICF = 28 L

H2O

ECF ICF

H2O

Osmotic Diuresis

Osmotic Diuresis ECF hyperosmolar from ICF autotransfusion

ECF an ICF !oth hyperosmolar

Pr or ty n t er or ty n t e


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Pr or ty n t er or ty n t e%reatment of%reatment of

#yper$lycemia Crisis#yper$lycemia Crisis Replacin$ volume de-citsReplacin$ volume de-cits ? normal saline? normal salineaccordin" to %* urine output and CH valueaccordin" to %* urine output and CH value

for old a"e* total de&cits around E-I liters'for old a"e* total de&cits around E-I liters'

Correctin$ hyperosmolarity Correctin$ hyperosmolarity to 344to 344milliosmoles/$milliosmoles/$

Mana$in$ any underlyin$ illnessesMana$in$ any underlyin$ illnesses

Insulin 0Insulin 0 R2 4'79u/#" bolus then 4'7/#"/hrR2 4'79u/#" bolus then 4'7/#"/hrinfusion until blood su"ar about 594m"/dl orinfusion until blood su"ar about 594m"/dl or

osmo about 379osmo about 379


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complications of diabetes mellitus-update

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