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Lecture 25
Insulin Dependent Diabetes Mellitus
Type 1 Diabetes
Juvenile Onset Diabetes
500 BC
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Frequent urination
Rapid loss of weight
Unquenchable thirst
“Sweet” breath
Death within a few weeks
– Diabetes
• Urine contains sugar
– Mellitus
Hypoinsulinemia
• Think about what insulin does
– Not just anabolic, also anti-catabolic
• Prevents
– Glycogenolysis
– Proteolysis
– Lipolysis
• Stimulates
– Glucose uptake and disposal
Lack of Insulin
• Poor glucose uptake into cells
– But not zero, and only muscle/WAT affected
– Will elicit a bit of hyperglycemia
• Poor lipogenesis & glycogenesis
– Of little consequence
• Massive, uncontrolled lipolysis
– Huge release of fatty acids into the bloodstream
• And glycerol
– High rates of fatty acid oxidation
• Inhibits glucose oxidation, glucose  lactate
– High rates of ketone body production
• Inhibts glucose metabolism in the brain
• Uncontrolled proteolysis
– Breakdown of tissues
– Release of amino acids into bloodstream
Lipolysis & Proteolysis
• Weight loss
– Dangerous loss of essential protein
• Increasing hyperglycemia
– High rates of gluconeogenesis
• Glycerol, amino acids & lactate as substrates
• Fatty acid oxidation stimulating pyruvate carboxylase
• Low insulin, increased cAMP  increased F16BPase
– Low rates of glucose disposal
• Blood acidity rises
– Fatty acids, lactate, ketone bodies all acidic
– Ketoacidosis
• Ketone bodies decarboxylate
– Acetone lost on breath
Hyperglycemia
• Glycosylation increases
– But long term
• Loss of glucose in urine
– Glucose reabsorbtion by kidneys reduced above
[glucose]blood =10 mM
• Osmolality of blood changes
– Draws water out of the tissues
– Massive thrist
• Increased water intake
– Increased urination
– Loss of electrolytes
Treatment
• Insulin
– Discovered & first used in 1922
• Tight control to avoid complications
– Blood glucose monitoring
– Tailored insulin injections
• Long and short acting forms
– Risk of hypoglycemia
• Hypoglycemia unawareness