Diabetes Mellitus (Part II) Treatment Acute Complications Chronic Complications Patient Teaching.
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$y of diabetic
retinopathy retinopathy
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Advanced diabetic eye Advanced diabetic eye
diseasediseaseRetinal ischemia
Pericyte
loss
Neovascularitation
Preretinal
haemorrhage
Neovascularglaucoma Vitroushaemorrhage !etinaldetachment
Blindness
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Diabetic retinopathy Diabetic retinopathy
%lindness is primarily the result of pro"ressive diabeticretinopathy and clinically si"ni&cant macular edema'
Diabetic retinopathy is classi&ed into to sta"esnonproliferative and proliferative'
Nonproliferative diabetic retinopathy : mar#ed by retinal vascular microaneurysms* blot hemorrha"es* and cottonool spots
+he appearance of neovasculari,ation in response to retinalhypoia is the hallmar# of proliferative diabeticretinopathy '
Duration of DM and de"ree of "lycemic control are the bestpredictors of the development of retinopathy. hypertensionis also a ris# factor
+he most eective therapy for diabetic retinopathy isprevention'
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Diabetic nephropathy Diabetic nephropathy
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Pathophysiolo$y of diabeticPathophysiolo$y of diabetic
nephropathy nephropathy Hyperglycemia
Renal
vasodilatation Increased
intraglomerular
capillary pressure
Protein glycation
Increased glomular
filtration rateHypertension
Increased
protein excretion
Microalbuminuria or
macroalbuminuria
Nephropathy
Glomurular
damage
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Diabetic nephropathy Diabetic nephropathy is the leadin" cause of 0SRD in the 1S'
2ndividuals ith diabetic nephropathy almost alays have diabeticretinopathy' +he sta"es of diabetic nephropathy are :
Hyperltration Microalbuminuria Overtproteinuria Declining GFR End tage renal failure
Microalbuminuria is de&ned as 34 to 344 m"/d in a 56-h collection or34 to 344 "/m" creatinine in a spot collection (preferred method)'
+he appearance of microalbuminuria (incipient nephropathy) in type7 DM is an important predictor of pro"ression to overt proteinuria(344 m"/d) or overt nephropathy'
!ypertension more commonly accompanies microalbuminuria orovert nephropathy in type 5 DM
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Diabetic nephropathy !treatment
+he optimal therapy for diabetic nephropathy isprevention' 2nterventions eective in sloin" pro"ression from
microalbuminuria to overt nephropathy include near normali,ation of "lycemia* strict blood pressure control* and
administration of AC0 inhibitors or AR%s* and treatment of dyslipidemia'
%lood pressure should be maintained at 734/84 mm!"in diabetic individuals ithout proteinuria'
A sli"htly loer blood pressure (759/:9) should beconsidered for individuals ith microalbuminuria or
overt nephropathy A consensus panel of the ADA su""ests modest
restriction of protein inta#e in diabetic individuals ithmicroalbuminuria (4'8 "/#" per day) or overtnephropathy (;4'8 "/#" per day)
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Diabetic neuropathy Diabetic neuropathy
h i f d i
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Mechanism of nerve dama$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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Pathophysiolo$y of diabeticPathophysiolo$y of diabetic
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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%han( your for your%han( your for your
attentionattention