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T1 DM S2 Pathophysiology
T1 DM S2 Pathophysiology
of Type 1 Diabetes
1
Type 1 Diabetes Mellitus
• Characterized by absolute insulin
deficiency
• Pathophysiology and etiology
– Result of pancreatic beta cell destruction
• Prone to ketosis
– Total deficit of circulating insulin
– Autoimmune
– Idiopathic
2
Type 1 Diabetes
Inflammation
• Beta cell destruction TNFa
FasL
IFNg
– Usually leading to
absolute
T cell
insulin deficiency
Autoimmune Reaction
• Immune mediated Macrophage
Class I
TNFa
MHC
• Idiopathic Class II
MHC
IL-1
Beta cell
NO CD8+ T cell
Dendritic cell
Beta cell Destruction
4
Maahs DM, et al. Endocrinol Metab Clin North Am. 2010;39:481-497.
Autoimmune Basis for
Type 1 Diabetes
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Autoantibodies to insulin, IAA; GAD, GADA; islet antigen-2, IA-2A; zinc transporter 8, ZnT8A.
Long AE, et al. Diabetes. 2012;61:683-686.
Etiological Approach to Diabetes
Type Characterization
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Consequences of Insulin
Deficiency
• Hyperglycemia osmotic diuresis and
dehydration
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Major Metabolic Effects of Insulin and
Consequences of Insulin Deficiency
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