Diabetes mellitus

[Ref: WG21:p343-]

Reduced entry of glucose into various tissues
* Muscle, adipose tissues
* Liver [see Insulin]
Increased release of glucose from liver, due to
* Absence of insulin
* Presence of glucagon
* Increased supply of amino acids
* Presence of catecholamine, cortisol, and growth hormone (in severe disease)
Increased lipolysis
--> Ketoacidosis

Glycosuria
--> Loss of large amount of water
--> Increased urinary loss of Na+ and K+
Coma
* Due to hyperosmolarity
* Independent of acidosis or dehydration

Long-term

Increased catabolism
* Protein and fat
Ketosis
* Due to fat catabolism
Hyperphagia
* Probably due to decreased glucose utilization in the cells of hypothalamic ventromedial nuclei
* [see Hunger]

Normally, ingested glucose...
* 30-40% converted to fat
* 5% converted to glycogen

In DM
* <5% converted to fat
* 5% converted to glycogen

Insulin normally
* Inhibits hormone-sensitive lipase

Absence of insulin
--> Overactivity of hormone-sensitive lipase
--> Increased release of FFA from adipose tissue
--> Plasma FFA more than doubled

Increased glucagon
--> Also increase release of FFA

Thus,

Increased FFA
--> Catabolized to acetyl-CoA
--> Excess acetyl-CoA overted to ketone bodies

Also,

Decreased activity of lipoprotein lipase
--> Decreased triglyceride uptake from chylomicrons
--> Increased plasma triglyceride

Excess acetyl-CoA
--> Acetoacetyl-CoA
--> Acetoacetate (in liver)

Ketone bodies:
* Acetoacetate
* Acetone
* Beta-hydroxybutyrate

Excess ketones
--> Acidosis
--> Kussmaul breathing (rapid deep respiration)

Other notes

[WG21:p345]

Ratio of glucose (dextrose) to nitrogen in urine

Used to estimate the rate of gluconeogenesis

Basis
= 1g of urinary nitrogen is sufficient to form 8.3g of glucose

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