Control of blood sugar

Blood sugar is tightly controlled in normal individuals. It normally ranges between 4 and 11 mmol/L. When food is digested and sugars are absorbed into the bloodstream from the gut, there follows a transient rise in blood glucose. After a meal, insulin is secreted, which counteracts this rise in blood sugar.

Insulin is the 'hormone of plenty' - signifying to the body that there is an abundance of nutrients, and a lack of insulin signals a lack of food. Insulin has multiple effects:

• Increasing cellular permeability to glucose (in many different tissues)
• Inhibiting gluconeogenesis
• Inhibiting glycogenolysis
• Increasing glycogen synthesis
• A general anabolic effect causing assimilation of lipid and protein in cells

Diabetes is diagnosed if a random blood sugar level is above 11.1 mmol/L, or fasting glucose exceeds 7.6 mmol/L. In type I diabetes mellitus, insulin secretion is impaired; in type II diabetes mellitus, the peripheral tissues become desensitised to insulin. The effect of both forms of diabetes is a post-prandial rise in glucose concentrations, arising to disruption of the normal negative feedback system.

Signs and symptoms of diabetes can include

• Polyuria (excess urine production) due to high concentrations of glucose in the urine. This is glucose that is filtered but which can't be reabsorbed, because the kidney has an upper limit on the rate of active reabsorption of glucose.
• Polydipsia (excessive thirst) - as compensation for the large volumes of urine lost due to the polyuria.
• Dehydration, especially if insufficient fluid is replaced by drinking.
• Weight loss, which reflects the body inappropriately entering a state of starvation. Although there is excess glucose, cells behave as though there is not enough fuel, and become catabolic. Glycogen, fat, and eventually protein will be used for energy.
• Ketosis, which is the body's natural response to starvation, and whose function is to provide an alternative form of energy for the brain. The brain can only utilise glucose and ketones for energy.

1. glycogenolysis = - ecf.glucose.error
   glycogen breakdown or synthesis if glucose is too low or high respectively
2. lipolysis = - ecf.glucose.error
   fat breakdown or synthesis if glucose is too low or high respectively
3. if (glycogenolysis < 0) glycogenolysis = glycogenolysis * blood.Insul
4. if (lipolysis < 0) lipolysis = lipolysis * blood.Insul
   glycogen synthesis and lipid synthesis are dependent on insulin
5. d/dt ecf.glucose = glycogenolysis + lipolysis
6. d/dt Glycogen = - glycogenolysis
7. d/dt Fat.mass = - lipolysis
   sugar is converted to/from glycogen and fat
8. blood.glucose <-> ecf.glucose
   blood sugar rapidly equilibrates with extracellular fluid
9. stomach.glucose --> blood.glucose
   absorption rate depends on stomach glucose
10. RespiratoryQuotient --> f(lipolysis / MetabolicRate)
    respiratory quotient depends on how much of the total metabolic rate uses up fat
11. d/dt blood.ketones = f(lipolysis, blood.Insul.error) - constant
    ketones synthesis proportional to lipid breakdown, dependent on low insulin; ketones used at constant rate
12. d/dt blood.Insul = max(0,ecf.glucose.error) + stomach.glucose.quantity - constant
    insulin released when there is excess extracellular sugar, or if there is food in the stomach; but also broken down rapidly from the bloodstream