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Complications of
Diabetes Mellitus
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Assesment of Glycemic Control
UrinalysisGlycosuriaLimitations of urinalysis : renal threshold (varies between
individual); urinary concentration (fluid intake and urineconcentration may effect); neuropathic bladder (reduce theaccuracy); hypoglycemia(this can not be detect)
Urinary ketonesSemi-quantitatif test for acetoacetat; Ketosis-prone diabetes
Glycated haemoglobin HbA1c is formed by the post-translational, non-enzymatic glycationGlycaemic targets
Frequency of measurement (every 3 or 6 months) Limitations of HbA1c measurements : daily patern of blood
glucose levels? ; blood loss/haemolysis/reduced red cell (lowHbA1c)
Blood glucose
Before breakfast (fasting) 2 hour post prandial
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mmol/l
1. ADA. Diabetes Care2004; 27: S1535; 2. ADA Diabetes Care2002; 25: S3549;
3. Feld S. Endoc rine Pract2002; 8 (Suppl 1): 4082; 4. Asian-Pacific Type 2 Diabetes Policy Group.
Type 2 diabetes: Practical targetsand treatment. 4th Edn; Hong Kong: Asian-Pacific Type 2 Diabetes Policy Group, 2005.
< 140< 180Postprandial plasma
glucose
< 11090130Fasting/preprandial
plasma glucose
Biochemical index AACE3ADA1,2 IDF4
(Western
Pacific region)
mg/dl mmol/l mg/dl mmol/l
mg/dl
< 6.15.07.2
< 10.0
< 6.5< 7HbA1c(%) < 6.5
< 110< 6.0
< 145< 7.8
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Konsensus PERKENI 2005
Current Indonesian Society of
Endocrinology (Perkeni) treatment targets
HbA1c < 7%
Fasting BG < 100
mg/dl Post prandial BG < 140
mg/dl
Blood pressure < 130/80mmHg
LDL-cholesterol < 100
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Complications of DiabetesMellitus
Chronic Complications ofDiabetes Mellitus
Microvascular
Macrovascular
Acute Complications ofDiabetes Mellitus
Hyperglycemia crisis
Hypoglycemia
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Pathophysiology ofMicrovascular
Complications
A ti ti f P t i Ki
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Activation of Protein Kinase
C
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Diabetic Retinopathy
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Diabetic Retinopathy
Blindness is primarily the result of progressive diabetic retinopathy andclinically significant macular edema.
Diabetic retinopathy is classified into two stages: nonproliferative andproliferative.
Nonproliferative diabetic retinopathy : marked by retinal vascularmicroaneurysms, blot hemorrhages, and cotton wool spots
The appearance of neovascularization in response to retinal hypoxia is
the hallmark ofproliferative diabetic retinopathy.
Duration of DM and degree of glycemic control are the best
predictors of the development of retinopathy; hypertensionis also a risk factor
The most effective therapy for diabetic retinopathy isprevention.
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Hyperglycemia
Renalvasodilatation Increased
intraglomerular
capillary pressure
Protein glycation
Increased glomular
filtration rateHypertension
Increased
protein excretion
Microalbuminuria or
macroalbuminuria
Nephropathy
Glomurular
damage
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Diabetic NephropathyDiabetic nephropathy is the leading cause of ESRD in the US.
Individuals with diabetic nephropathy almost always have diabeticretinopathy.
The stages of diabetic nephropathy are:
Hyperfiltration
Microalbuminuria
Overtproteinuria
Declining GFR
End stage renal failure
Microalbuminuria is defined as 30 to 300 mg/d in a 24-h collection
or 30 to 300 g/mg creatinine in a spot collection (preferredmethod).
The appearance of microalbuminuria (incipient nephropathy) intype 1 DM is an important predictor of progression to overtproteinuria (300 mg/d) or overt nephropathy.
Hypertension more commonly accompanies microalbuminuria orovert nephropathy in type 2 DM
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Diabetic Nephropathy -
Treatment The optimal therapy for diabetic nephropathy is
prevention. Interventions effective in slowing progression from
microalbuminuria to overt nephropathy include: near normalization of glycemia, strict blood pressure control, and
administration of ACE inhibitors or ARBs, and treatment of dyslipidemia.
Blood pressure should be maintained at 130/80 mmHgin diabetic individuals without proteinuria.
A slightly lower blood pressure (125/75) should beconsidered for individuals with microalbuminuria orovert nephropathy
A consensus panel of the ADA suggests modestrestriction of protein intake in diabetic individuals withmicroalbuminuria (0.8 g/kg per day) or overtnephropathy (
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METABOLIC VASCULAR
glucose
sorbitol
H2O
nerve
oedema
myoinositol
NO
production
AGE
formation
vasoconstriction
Arterial
narrowing
Vessel
occlusion
Slow nerve
conduction
Impairingaxonal transport
Altered membrane
potensial
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Diabetic Neuropathy
Diabetic neuropathy occurs in approximately 50% ofindividuals with long-standing type 1 and type 2 DM. The development of neuropathy correlates with the duration
of diabetes and glycemic control; both myelinated andunmyelinated nerve fibers are lost.
Several stage :
Intraneural biochemical abnormalities; sorbitolaccumulation, myoinositol depletion Impairement of electrophysiological measurement;
decreased nerve conduction velocity; asymptomatic Clinical neuropathy; detectable using clinical methods;
maybe symptomatic. Histological changes evident End stage complications. Exp are ulceration and Charcot
neuroarthropathy; major derangements of neuralstructure and function.
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Clinical Features Symmetrical
Sensorimotor NeuropathySymptoms Loss of
sensation ;
Anaesthesia;numbness Loss of pain
perception
Altered
sensation: Paraesthesiae Dysaesthesiae
Pain
Burning
Signs
Sensory loss
Diminished/absent tendon
reflexs Muscle wasting and
weakness
Autonomic dysfunction
Foot uleration
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Burning, feeling like the feet are on fire Freezing, like the feet are on ice,although they feel warm to touch
Stabbing, like sharp knives Lancinating, like electric shocks
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Treatment of Symmetric
Neuropathy
Glucose control
Pain control
Tricyclic antidepressants Amitriptyline,desipramin, nortriptilin,
trazodone
Anticonvulsants
Carbamazepine, gabapentin Topical creams
capsaicin
Foot care
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Macrovascular Complication
Macrovascular complications of diabetes mellitusare condition characterized by atheroscleroticocclusive disease of cerebral, myocard andlower extremities.
Atherothrombosisis the most common cause ofmacrovascular complications
Atherothrombosis is characterized by a sudden(unpredictable) atherosclerotic plaque disruption
(rupture or erosion) leading toplatelet activationand thrombus formation
Atherothrombosis is the underlying condition thatresults in events leading to myocardial infarction,
ischemic stroke, amputation and vascular death
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Macrovascular Disease in
Diabetes Mellitus Cardiovascular and cerebrovascular disease account
for up 70% of death in patients with type 2 DM All patients with type 2 diabetes have greater
predipostition to macrovascular disease, often having aconstellation of risk factors, which have been terminsulin resistance.
It has been hypotethesized that insulin resistance andhyperinsulinemia (environmental and genetic factors),are central to development : Glucose intolerance
Hypertension Dyslipidemia Coagulopathy
These factors promote accelerated atherosclerosis,explaining the increased risk of macrovascular disease.
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Di b t d M l
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Diabetes and Macrovascular
Disease
Libby and Plutsky. Circulation.2002.
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Strategies for Reducing
Macrovascular Complications Prevention proven intervention trials
Hyperglycemia
Dyslipidemia
Hypertension
Antiplatelet therapies
Prevention suggested by epidemiologicanalysis
Disorders of thrombolysis
Endothelial disorders
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The Diabetic Foot
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Diabetic Foot Disease
Approximately 15% of individuals with DM develop a
foot ulcer, and a significant subset will ultimatelyundergo amputation (14 to 24%risk with that ulcer orsubsequent ulceration).
Syndrome of diabetic foot disease Peripheral neuropathy, peripheral vascular disease
and tissue infection Risk factors for foot ulcers or amputation include: male
sex, diabetes 10 years duration, peripheral neuropathy,abnormal structure of foot (bony abnormalities,callus,thickened nails), peripheral arterial disease, smoking,history of previous ulcer or amputation, and poor
glycemic control. The plantar surface of the foot is the most common siteof ulceration.
Ulcers may be primarily neuropathic (no accompanyinginfection) or may have surrounding cellulitis orosteomyelitis.
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Neuropathy
Motor
dysfunction
Neuropathy Neuropathy
Abnormal
Foot posture
Cheiroarthropathy
Reduced pain
Sensation and
proprioception
Increased foot
prssure
Callus
Microvascular
disease
Poor tissue
nutrition and
oxygenation
Ulcer
Macrovascular
diseaseIschemia
Dry, cracked
skin
Arteriovenousshunting
TraumaMechanical,
thermal,
chemical
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Acute Complication of Diabetes
Mellitus
Hyperglycemia crisis
Diabetic ketoacidosis (DKA)
Hyperglycemic Hyperosmolar
State (HHS)
Hypoglycemia
Pathophysiolgy of Hyperglycemia
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Pathophysiolgy of Hyperglycemia
Crisis
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Diabetic Ketoacidosis (DKA)
DKA was formerly considered a hallmark of type 1DM
The symptoms and physical signs of DKA
Symptoms : Nausea/vomiting, Thirst/polyuria,Abdominal pain, Shortness of breath
Physical findings : Tachycardia, Dry mucousmembranes/reduced skin turgor, Dehydration /hypotension, Tachypnea / Kussmaul
respirations/respiratory distress, Abdominaltenderness (may resemble acute pancreatitis or
surgical abdomen), Lethargy /obtundation /cerebral edema / possibly coma
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Precipitating Factors
Inadequate insulin administration
Infection (pneumonia/UTI )
Gastroenteritis/sepsis
Infarction (cerebral, coronary,
mesenteric, peripheral)
Drugs (cocaine)
Pregnancy
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Precipitating Factors
Infection ( the most common)
Cerebrovascular accident
Alcohol abuse
Pancreatitis
Myocardial infarction
Trauma
Drugs
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Clinical Findings of HHS
HHS should be suspect : elderly patient with orwithout the preexisting diagnosis of diabetes whoexhibits acute or subacute deterioration of CNSfunction and severely dehydrated
Tachycardia Low grade fever
Low or normal blood pressure
Dehydrationdry mucous membrane, absent
axillary sweat, poor skin turgor. Nausea, vomiting, distension, and pain-
gastroparesis is due to hypertonicity
Lethargy, hallucinations, and psychosis
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Priority in the Treatment of
Hyperglycemia Crisis
Replacing volume deficitsnormal saline
according to BP, urine output and CVP value for
old age, total deficits around 6-9 liters.
Correcting hyperosmolarity to 300
milliosmoles/L
Managing any underlying illnesses
Insulin ; RI 0.15u/kg bolus then 0.1/kg/hrinfusion until blood sugar about 250mg/dl or
osmo about 315
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Approach to Therapy
Correcting the hyperosmolar state and
dehydration is the initial aim of therapy.
Insulin therapy should be undertaken
only after the patient is stable
hemodynamically.
Glucose and H2O
H2O lost in urine Loss of ECF, vascular collapse and death
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Hypoglycemia
Clinical Manifestations of
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Clinical Manifestations of
Hypoglycemia Whipples triadsymptoms consistent with hypoglycemia,a low
plasma glucose concentration,and relief of those symptoms when the
plasma glucose concentration is raisedprovides compellingevidence of hypoglycemia.
Symptoms of hypoglycemia can be divided into two categories,neuroglycopenic and neurogenic (autonomic) symptoms.
Neuroglycopenic symptoms are the direct result of CNSneuronal glucose deprivation. They include behavioral changes,
confusion,fatigue or weakness, warmth, visual changes, seizure,loss of consciousness,and,if hypoglycemia is severe andprolonged, death. ( BG < 20 mg/dL )
Neurogenic symptoms are the result of the perception ofphysiologic changes caused by the autonomic nervous systemdischarge triggered by hypoglycemia. ( BG 50 mg/dL )
They include adrenergic symptoms such aspalpitations,tremor, and anxiety and cholinergic symptomssuch as sweating,hunger, and paresthesias.
Cholinergic symptoms,at least sweating, are thought to bemediated by acetylcholine released from sympatheticpostganglionic neurons.
Comprehensive Risk Factors for
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Comprehensive Risk Factors for
Hypoglycemia in DiabetesPremise: Iatrogenic hypoglycemia in type 1 diabetes is the
result of the interplay of therapeutic insulin excess andcompromised glucose counterregulation.1. Absolute or relative therapeutic insulin excess (the
conventional risk factors)a. Insulin doses excessive,ill-timed, wrong typeb. Decreased food intake
c. Increased glucose utilization (e.g.,exercise)d. Decreased glucose production (e.g.,alcohol)e. Increased sensitivity to insulin (e.g.,after exercise,during the
night,glycemic control, weight loss)f. Decreased insulin clearance (e.g.,renal failure)
2. Compromised glucose counterregulationa. Absolute insulin deficiency (C-peptide negativity)
Cell destruction: No in insulin in response to glucoseUnknown: No in glucagon in response to glucose
b. History of severe hypoglycemia or aggressive therapy per se (lowerglucose goals,lower hemoglobin A1c)
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Management of Acute Hypoglycemia
Acute hypoglycemia
Oral glucose
(10-20gr)
30-50 ml Dextrose 40% or
Glucagon 1mg sc/im
Check BG after
15-20 min
Acute hypoglycemia
Repeat oral
glucose10% glucose
IV infusion
Patient
conscious
Patient
unconscious
Recovered Notrecoverd
Patient
unconscious Patientconscious
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Thank you