Professional Documents
Culture Documents
PATHOPHYSIOLOGY
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“ Type 1 diabetes is an
autoimmune disease in which
islet destruction is caused
primarily by immune effector
cells reacting against
endogenous B-cell antigens.
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Ketoacidosis
Type 1 DM – The Autoimmune Disease and coma
Or else
Genetic susceptibility
• A disease of genetic and environmental risks
• HLA-DR3 or -DR4 with DQ8 (High risk)
• Erroneous T-cell selection
• Molecular mimicry
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Age
B cell mass
Features of DM –
Not evident until 70-
80% of the B-cells
are destroyed
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Honeymoon phase
• 1-2 years after
initial onset of ssx
• Glycemic control
achieved
• Modest or no
insulin at all is
needed
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Type 1 DM – The Autoimmune Disease
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• Pancreatic islets: Insulitis, modest
infiltration of lymphocytes -> atrophy
• Destruction more by T lymphocytes
• Triggers: Coxsackie, rubella, enteroviruses
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Type 2 DM
Non-autoimmune | Resistance
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“ Type 2 diabetes is a complex
disease that involves an
interplay of genetic and
environmental factors and a pro-
inflammatory state. No evidence
of autoimmune basis.
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“ Type 2 diabetes is a complex
disease that involves an
interplay of genetic and
environmental factors and a pro-
inflammatory state. No evidence
of autoimmune basis.
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Type 2 DM - The Diabetes of Obesity
Environmental
Genetic Factors
Factors
Highly heritable
Obesity (> 80%,
– 1st degree
central or visceral,
relatives have 5-
most important)
10-fold risk
Sedentary lifestyle
(Lack of exercise)
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Type 2 DM – The Cardinal Metabolic Defects
1. 2.
Decreased response of Inadequate insulin
peripheral tissues, secretion in the face of
especially skeletal muscle, insulin resistance and
adipose tissue, and liver, hyperglycemia (B-cell
to insulin dysfunction)
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Type 2 DM – The Cardinal Metabolic Defects
Insulin resistance 2.
-> Hyperglycemia Inadequate insulin
-> B-cell secretion in the face of
hyperfunction and insulin resistance and
hyperinsulinemia hyperglycemia (B-cell
dysfunction)
(early stages)
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INSULIN RESISTANCE
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Insulin Resistance: Failure -
To inhibit
Of glucose
lipoprotein
uptake and
To inhibit lipase in
glycogen
endogenous adipose tissue
synthesis to
glucose -> excess
occur in skeletal
production in circulating free
muscle following
the liver -> high fatty acids
a meal -> high
fasting blood (FFAs) ->
post-prandial
glucose levels amplify the state
blood glucose
of insulin
level
resistance
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How can exercise improve
insulin sensitivity?
Increased
TRANSLOCATION
of GLUT-4 to the
surface of skeletal
muscle cells
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SO WHAT IS REALLY THE RELATIONSHIP
BETWEEN OBESITY AND INSULIN RESISTANCE?
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▰ Central adipose: More lipolytic
▰ Excess FFAs -> DAG ->
Free Fatty Acids Attenuate signalling through
insulin receptor pathway ->
Increased gluconeogenesis
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B-Cell Dysfunction
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Promoting B-cell dysfunction
Impact of
genetics Abnormal “incretin
effect”: Reduced
Amyloid GIP and GLP-1
deposition which promote insulin
within islets relsease
(long-standing)
Chronic
Excess FFAs hyperglycemia
(Lipotoxicity) (Glucotoxicity) 29
Monogenic Forms of Diabetes
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Thank you!
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