explains in detail abou various complications of diabetes mellitus and its pathophysiology. Described about the peripheral, microvascular, macrovascular comlpication

1. welcome
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2. COMPLICATION
OF
DIABETES MELLITUS
By
AISWARYA
2nd year Pharm.D
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3. DIABETES MELLITUS
 Diabetes mellitus is a group of metabolic
disorder characterized by HYPERGLYCEMIA
 Its associated with abnormalities in the
carbohydrate, fat , and protein metabolism and
it is mainly due to the defect in insulin secretion
, insulin action or both
 Diabetes mellitus results in chronic complication
including
a)Micro vascular diseases
b)Macro vascular diseases
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4. Micro vascular complication
includes
a)Diabetic retinopathy
b)Diabetic nephropathy
c)Diabetic neuropathy
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5. DIABETIC RETINOPATHY
 Most common microvascular complication .
 It eventually leads to BLINDNESS .
 It affect 80% of all patient who had diabetes for 10
years or more .
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7.  The longer a person had diabetes , the higher
his chances of developing retinopathy .
 Development of diabetic retinopathy in
patients with type 2 diabetes was found to be
related to both severity of hyperglycemia and
presence of hypertension .
 VEGF(Vascular endothelial growth factor)
production is increased in diabetic
retinopathy .
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8. PATHOGENESIS OF DIABETIC
RETINOPATHY
 In the first stage which is called non proliferated
diabetic retinopathy (NPDR)there are no symptom .
 Diabetic retinopathy is result of micro vascular
retinal change .
 Hyperglycemia induced intramural pericyte death
and thickness of basement membrane lead to
incompetence of the vascular wall .
 This damage change the formation of blood retinal
barrier and also make the retinal blood vessel more
permeable .
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9.  Small blood vessels in the eye are vulnerable
to poor blood sugar , cause accumulation of
glucose and fructose and thus damage the
tiny blood vessel in the retina .
 Here is a chance of developing MACULAR
EDEMA .
 When the macula swells with fluid ,macular
edema occurs .That causes blurred vision .
 No loss of vision.
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11.  PROLIFERATIVE DIABETIC RETINOPATHY
 New blood vessels grow along the retina and in the
vitreous chamber and humorous chamber of the eye.
 Damaged blood vessel close off. New blood vessel
start growing in retina ;these blood vessel are weak
and leaky and thus block vision.
 The new blood vessel can also cause scar tissue to
grow , later it shrinks and distort the retina out of its
place ; a condition called RETINAL DETACHMENT
 Thus there is loss of vision
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12. DIABETIC NEUROPATHY
 Diabetic neuropathy are neuropathic disorder that
are associated with diabetes mellitus.
 It resulting from injury of small blood vessels that
supply nerves.
 Diabetic neuropathy affects all peripheral nerves
including pain fibers , motor neurons and the
autonomic nervous system . It therefore can affect
all organ and system as all are innervated.
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13. TYPESOF DIABETIC
NEUROPATHY
 Peripheral neuropathy: it can cause
tingling , pain , numbness , or
weakness in feet and hands .
 Autonomic neuropathy : affects the
nerves in the body that control our
body system .
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15. SIGNS AND SYMPTOMS
 Numbness and tingling of extremities
 Dysesthesia
 Diarrhea
 Erectile dysfunction
 Dizziness
 Vision change
 Muscle weakness
 Speech impairment
 Fasciculation
 Burning or electric pain
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16. PATHOGENESIS OF DIABETIC
NEUROPATHY
4 Factor involving development of diabetic neuropathy
 MACROVASCULAR DISEASES
 Micro angiopathy , vascular and neural diseases are
closely related and intervened
 Blood vessels depend on normal nerve function
,and nerves depend on adequate blood flow.
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17.  The first pathologic change include
VASOCONSTRICTION
 As the diseases progresses , neuronal dysfunction
correlates with development of vascular abnormalities
like capillary basement membrane thickening and
endothelial hyperplasia, which diminished oxygen
tension and hypoxia
 Neural ischemia is well established characteristic
feature of diabetic neuropathy
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18.  ADVANCED GLYCATED END PRODUCTS
 AGEs are substance that are formed by the
process of Glycation (non enzymatic
glycosylation; addition of a carbohydrate to
protein without involvement of enzyme) .
 AGEs can be a factor in the development or
worsening of many degenerative diseases such
as diabetes, atherosclerosis and chronic renal
failure.
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19.  Elevated intracellular level of
glucose cause non enzymatic
covalent bonding with proteins ,
making cell stiffer ,less pliable and
more subjected to damage and
premature aging of skin .
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20.  PROTEIN KINASE C
 Increasing levels of glucose cause an increases
intracellular diacylglycerol , which activates PKC
(PKC inhibitor increases nerve conduction velocity
by increasing neuronal blood flow) .
 Increased diacyglycerol causes hyperglycemia and
thus DIABETES MELLITUS
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21.  POLYOL PATHWAY
 Its also called sorbitol / aldose reductase pathway.
Especially in microvascular damage to retina ,
kidney, and nerves .
 Sorbitol cannot cross cell membranes , and , when
it accumulates , it produces osmotic stresses on the
cells by drawing water into the insulin – independed
tissues .
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22. DIABETIC NEPHROPATHY
 Also known as nodular diabetic glomerulosclerosis and intra
capillary glomerulonephritis
 It is a progressive kidney disease caused by angiopathy of
capillaries in the kidney glomerulii
 It is characterized by nephrotic syndrome
 Screening of diabetic nephropathy is accomplished by either a
24 hrs urine collection or a spot urine measurement
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23. SIGNS AND SYMPTOMS
 Fluid retention plus reduced plasma oncotic
pressure causing EDEMA
 Anorexia
 Nausea and vomiting
 Malaise
 Fatigue
 Head ache
 Weight gain
 Excess glucose in urine
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25. PATHOGENESIS OF DIABETIC
NEPHROPATHY
 Detectable change in the course of diabetic
nephropathy is a thickening of the glomerulus
, micro aneurysm formation , messaginal
nodule formation and other changes .
 At this stage kidney may leak more serum
albumin than normal in the urine (
albuminurea ).
 As it progresses, increasing number of
glomeruli are destroyed by progressive
nodular glomerulosclerosis
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26. MACROVASCULAR
COMPLICATIONS
 Macrovascular disease is a diseases of any
large(macro) blood vessels in the body
 Diseases includes
a)Cardiovascular diseases
b)Cerebrovascular diseases
c)Peripheral vascular diseases
 Macrovascular disease (macroangiopathy)
refer to ATHEROSCLEROSIS
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27. CARDIO VASCULAR
DISEASES
 CVD is the leading cause(~70%) of death in
people with type 2 diabetes mellitus .
 They cause myocardial
infarction(MI),congestive heart failure(CHF) .
 Factors that promote CVD are:
 Abdominal obesity
 Hypertension
 Hyperlipidemia
 Increased coagulability
 Even with multiple risk factor for the ischemic
heart disease , stroke ,coronary heart disease and
death .
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28. PERIFERAL VASCULAR
DISEASES
 PVD affects the blood vessels outside the heart .
 In persons with diabetes , it often affects the
arteries of the legs and may give rise to
intermittent CLAUDICATION - a cramping pain
experienced on walking , due to reversible muscle
ischemia secondary to atherosclerosis .
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29.  PVD is responsible for much of the morbidity
associated with Diabetic foot problems .
 About 20% of people with PVD die from Myocardial
infarction within 2 years of symptom onset .
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30. CEREBRO VASCULAR
DISEASES
 Patients with type 2 diabetes mellitus have
a much higher risk of stroke , with an
increased 150-400% .
 Risk of stroke related dementia and
recurrence , as well as mortality is
elevated in patients with diabetes.
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31. REFERENCE:
Complications of diabetes mellitus
 Source:
http://en.wikipedia.org/wiki/Complications_of_diabet
es_mellitus?oldid=618313885
 Clinical pharmacy and Therapeutics - Roger and
Walker , Churchill Livingstone
 Pharmacotherapy : A pathophysiological approach -
Joseph T . Dipiro et al . Appleton & Lange .
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