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Diabetes Mellitus
Assesment of Glycemic Control
Urinalysis
Glycosuria
Limitations of urinalysis : renal threshold (varies between
individual); urinary concentration (fluid intake and urine
concentration may effect); neuropathic bladder (reduce the
accuracy); hypoglycemia (this can not be detect)
Urinary ketones
Semi-quantitatif test for acetoacetat; Ketosis-prone diabetes
Glycated haemoglobin
HbA1c is formed by the post-translational, non-enzymatic glycation
Glycaemic 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 (low
HbA1c)
Blood glucose
Before breakfast (fasting)
2 hour post prandial
ADA, AACE and IDF Glycaemic Goals
Biochemical index ADA1,2 IDF4
AACE3 (Western
Pacific region)
HbA1c (%) <7 < 6.5 < 6.5
mg/dl mmol/l mg/dl mmol/l mg/dl mmol/l
Fasting/preprandial 5.07.2 < 6.1
90130 < 110 < 6.0 < 110
plasma glucose
Postprandial plasma
glucose < 180 < 10.0 < 140 < 7.8 < 145 <8.0
1. ADA. Diabetes Care 2004; 27: S1535; 2. ADA Diabetes Care 2002; 25: S3549;
3. Feld S. Endocrine Pract 2002; 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.
Current Indonesian Society of
Endocrinology (Perkeni) treatment targets
HbA1c < 7%
Fasting BG < 100
mg/dl
Post prandial BG < 140
mg/dl
Blood pressure < 130/80
mmHg
LDL-cholesterol < 100
Konsensus PERKENI 2005
Complications of Diabetes
Mellitus
Chronic Complications of Acute Complications of
Diabetes Mellitus Diabetes Mellitus
Microvascular Hyperglycemia crisis
Hypoglycemia
Macrovascular
Pathophysiology of
Microvascular
Complications
Activation of Protein Kinase
C
Diabetic Retinopathy
Diabetic Retinopathy
Blindness is primarily the result of progressive diabetic retinopathy and
clinically significant macular edema.
Diabetic retinopathy is classified into two stages: nonproliferative and
proliferative.
Nonproliferative diabetic retinopathy : marked by retinal vascular
microaneurysms, blot hemorrhages, and cotton wool spots
The appearance of neovascularization in response to retinal hypoxia is
the hallmark of proliferative diabetic retinopathy.
Duration of DM and degree of glycemic control are the best
predictors of the development of retinopathy; hypertension
is also a risk factor
The most effective therapy for diabetic retinopathy is
prevention.
Diabetic Nephropathy
Hyperglycemia
Microalbuminuria or Glomurular
macroalbuminuria damage
Nephropathy
Diabetic Nephropathy
Diabetic nephropathy is the leading cause of ESRD in the US.
Individuals with diabetic nephropathy almost always have diabetic
retinopathy.
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 (preferred
method).
The appearance of microalbuminuria (incipient nephropathy) in
type 1 DM is an important predictor of progression to overt
proteinuria (300 mg/d) or overt nephropathy.
Hypertension more commonly accompanies microalbuminuria or
overt nephropathy in type 2 DM
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 mmHg
in diabetic individuals without proteinuria.
A slightly lower blood pressure (125/75) should be
considered for individuals with microalbuminuria or
overt nephropathy
A consensus panel of the ADA suggests modest
restriction of protein intake in diabetic individuals with
microalbuminuria (0.8 g/kg per day) or overt
nephropathy (<0.8 g/kg per day)
Diabetic Neuropathy
METABOLIC VASCULAR
myoinositol
glucose
Altered membrane
potensial
Arterial
Slow nerve sorbitol narrowing
conduction AGE
formation
nerve vasoconstriction
oedema NO
production
Impairing
axonal transport
Vessel
occlusion
H2O
Diabetic Neuropathy
Diabetic neuropathy occurs in approximately 50% of
individuals with long-standing type 1 and type 2 DM.
The development of neuropathy correlates with the duration
of diabetes and glycemic control; both myelinated and
unmyelinated nerve fibers are lost.
Several stage :
Intraneural biochemical abnormalities; sorbitol
accumulation, 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 neural
structure and function.
Clinical Features Symmetrical
Sensorimotor Neuropathy
Symptoms Signs
Loss of Sensory loss
sensation ; Diminished/absent tendon
Anaesthesia;nu reflexs
mbness
Muscle wasting and
Loss of pain
perception weakness
Autonomic dysfunction
Altered
sensation: Foot uleration
Paraesthesiae
Dysaesthesiae
Pain
Burning
Burning, feeling like the feet are on fire Freezing, like the feet are on ice,
although they feel warm to touch
Macrophages
bind to and enter
intima wall
Macrophages
become foam Chemo-attractants such as PDGF
Uptake of Lipids by cells & fatty released from activated macrophages
Macrophages streak formed
Myocardial
infarction Angina:
Stable
Unstable
Reduced pain
Sensation and
proprioception
Abnormal
Foot posture
Arteriovenous
shunting
Callus
Ulcer
Mechanical,
Trauma thermal, Macrovascular
chemical Ischemia
disease
Acute Complication of Diabetes
Mellitus
Hyperglycemia crisis
Diabetic ketoacidosis (DKA)
Hyperglycemic Hyperosmolar
State (HHS)
Hypoglycemia
Pathophysiolgy of Hyperglycemia
Crisis
Diabetic Ketoacidosis (DKA)
Extreme hyperglycemia
Increased serum osmolality
Severe dehydration without significant
ketosis or acidosis
Hypoglycemia
Whipples triadsymptoms consistent with hypoglycemia,a low
plasma glucose concentration,and relief of those symptoms when the
plasma glucose concentration is raisedprovides compelling
evidence of hypoglycemia.
Symptoms of hypoglycemia can be divided into two categories,
neuroglycopenic and neurogenic (autonomic) symptoms.
Neuroglycopenic symptoms are the direct result of CNS
neuronal glucose deprivation. They include behavioral changes,
confusion,fatigue or weakness, warmth, visual changes, seizure,
loss of consciousness,and,if hypoglycemia is severe and
prolonged, death. ( BG < 20 mg/dL )
Neurogenic symptoms are the result of the perception of
physiologic changes caused by the autonomic nervous system
discharge triggered by hypoglycemia. ( BG 50 mg/dL )
They include adrenergic symptoms such as
palpitations,tremor, and anxiety and cholinergic symptoms
such as sweating,hunger, and paresthesias.
Cholinergic symptoms,at least sweating, are thought to be
mediated by acetylcholine released from sympathetic
postganglionic neurons.
Comprehensive Risk Factors for
Hypoglycemia in Diabetes
Premise: Iatrogenic hypoglycemia in type 1 diabetes is the
result of the interplay of therapeutic insulin excess and
compromised glucose counterregulation.
1. Absolute or relative therapeutic insulin excess (the
conventional risk factors)
a. Insulin doses excessive,ill-timed, wrong type
b. 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 counterregulation
a. Absolute insulin deficiency (C-peptide negativity)
Cell destruction: No in insulin in response to glucose
Unknown: No in glucagon in response to
glucose
b. History of severe hypoglycemia or aggressive therapy per se (lower
glucose goals,lower hemoglobin A1c)
Management of Acute Hypoglycemia
Acute hypoglycemia
Patient Patient
conscious unconscious