Diabetes mellitus

[Ref: WG21:p343-]

Fundamental defect

• 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

[See Gluconeogenesis]

Effect of hyperglycaemia

• 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

• Elevated HbA1c 

 

Effects of intracellular glucose deficiency

• 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]

Changes in fat metabolism

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

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

Increase in FFA

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

 

Ketosis

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

Ketone bodies:
* Acetoacetate
* Acetone
* Beta-hydroxybutyrate

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

 

Other complications

• Acidosis + dehydration
  --> Coma
• Lactic acidosis
• Infection

 

Other notes

 

D/N ratio

[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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