Escolar Documentos
Profissional Documentos
Cultura Documentos
of Diabetes
Mellitus
Urinary ketones
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
ADA1,2
AACE
3
<7
< 6.5
IDF4
(Western
Pacific
region)
< 6.5
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.
< 7%
Fasting BG
Post prandial BG
Blood pressure
LDL-cholesterol
mmol/l)
HDL-cholesterol
Men
> 40 mg/dl (1.1 mmol/l)
Women > 50 mg/dl (1.3 mmol/l)
Triglycerides
mmol/l)
Konsensus PERKENI
< 150 mg/dl (1.7
2005
Complications of Diabetes
Mellitus
Chronic Complications of
Diabetes Mellitus
Microvascular
Retinopathy
(nonproliferative/proliferative)
Nephropathy
Neuropathy
Acute Complications of
Diabetes Mellitus
Hyperglycemia crisis
Diabetic ketoacidosis
Hyperglycemia
hyperosmolar State
Lactic acidosis
Hypoglycemia
Pathophysiology of
Microvascular
Complications
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
Renal
vasodilatation
Increased glomular
filtration rate
Protein glycation
Increased
intraglomerular
capillary pressure
Hypertension
Increased
protein excretion
Microalbuminuria or
macroalbuminuria
Glomurular
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
Diabetic Neuropathy
myoinositol
VASCULAR
glucose
Altered membrane
potensial
Slow nerve
conduction
sorbitol
nerve
oedema
AGE
formation
Arterial
narrowing
vasoconstriction
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.
Altered sensation:
Paraesthesiae
Dysaesthesiae
Pain
Burning
Hyperalgesia/allodynia
Neuralgia lancinating
pain
Cramps ; restless leg
Signs
Sensory loss
Diminished/absent
tendon reflexs
Muscle wasting and
weakness
Autonomic
dysfunction
Foot uleration
Treatment of Symmetric
Neuropathy
Glucose control
Pain control
Tricyclic antidepressants
Amitriptyline,desipramin, nortriptilin, trazodone
Anticonvulsants
Carbamazepine, gabapentin
Topical creams
capsaicin
Foot care
Autonomic Neuropathy
DM-related autonomic neuropathy can involve multiple
systems, including the cardiovascular, gastrointestinal,
genitourinary, sudomotor, and metabolic systems.
Autonomic neuropathies affecting the cardiovascular system
cause a resting tachycardia and orthostatic hypotension.
Gastroparesis and bladder emptying abnormalities are often
caused by the autonomic neuropathy seen in DM (discussed
below).
Hyperhidrosis of the upper extremities and anhidrosis of the
lower extremities result from sympathetic nervous system
dysfunction.
Anhidrosis of the feet can promote dry skin with cracking,
which increases the risk of foot ulcers.
Autonomic neuropathy may reduce counterregulatory
hormone release, leading to an inability to sense
hypoglycemia appropriately ((hypoglycemia unawareness)
Pathophysiology of
Macrovascular
Complications
Macrovascular Complication
Macrovascular complications of diabetes mellitus
are condition characterized by atherosclerotic
occlusive disease of cerebral, myocard and lower
extremities.
Atherothrombosis is the most common cause of
macrovascular complications
Atherothrombosis is characterized by a sudden
(unpredictable) atherosclerotic plaque disruption
(rupture or erosion) leading to platelet activation
and thrombus formation
Atherothrombosis is the underlying condition that
results in events leading to myocardial infarction,
ischemic stroke, amputation and vascular death
Macrophages
bind to and enter
intima wall
Uptake of Lipids by
Macrophages
Macrophages
become foam
cells & fatty
streak formed
Smooth muscle
cells (SMCs)
migrate into the
intima
Myocardial
infarction
Angina:
Stable
Unstable
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 a
constellation of risk factors, which have been term insulin
resistance.
It has been hypotethesized that insulin resistance and
hyperinsulinemia (environmental and genetic factors), are
central to development :
Glucose intolerance
Hypertension
Dyslipidemia
Coagulopathy
Pathophysiology of Diabetic
Foot
Neuropathy
Motor
dysfunction
Abnormal
Foot posture
Microvascular
disease
Neuropathy Neuropathy
Reduced pain
Sensation and
proprioception
Increased foot
prssure
Dry, cracked
skin
Poor tissue
nutrition and
oxygenation
Cheiroarthropathy
Arteriovenous
shunting
Callus
Trauma
Mechanical,
thermal,
chemical
Ulcer
Ischemia
Macrovascular
disease
Acute Complication of
Diabetes Mellitus
Hyperglycemia crisis
Diabetic ketoacidosis (DKA)
Hyperglycemic Hyperosmolar State
(HHS)
Hypoglycemia
Pathophysiolgy of Hyperglycemia
Crisis
Precipitating Factors
Inadequate insulin administration
Infection (pneumonia/UTI )
Gastroenteritis/sepsis
Infarction (cerebral, coronary, mesenteric,
peripheral)
Drugs (cocaine)
Pregnancy
often 30-50%
Definition of HHS
Extreme hyperglycemia
Increased serum osmolality
Severe dehydration without significant ketosis or
acidosis
Precipitating Factors
Infection ( the most common)
Cerebrovascular accident
Alcohol abuse
Pancreatitis
Myocardial infarction
Trauma
Drugs
Laboratory Findings
DKA
HHS
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.
Hypoglycemia
Clinical Manifestations of
Hypoglycemia
Management of Acute
Hypoglycemia
Acute hypoglycemia
Patient
conscious
Patient
unconscio
us
Oral glucose
(10-20gr)
Recovere
d
Acute hypoglycemia
Check BG after
15-20 min
Not
recoverd
Patient
unconscio
us
10% glucose
IV infusion
Patient
conscious
Repeat oral
glucose
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