Starved State vs. Diabetes

Question 1

Diabetes Mellitus

Answer 1

Definition: diabetes is a heterogenous group of syndromes characterized by elevated fasting blood glucose caused by an insufficient or an absolute deficiency in insulin

Two types:

Type 1 = insulin-dependent

Type 2 = non-insulin dependent

Question 2

Describe Type 1 Diabetes

Answer 2

Caused by: autoimmune attack on beta-cells of the pancreas

Symptoms appear: abruptly when 80-90% of beta-cells destroyed

Lack of insulin signals: NO insulin/glucagon ratio

• Liver = overproduction of glucose
• Tissues = underutilization of glucose
• Liver = uncontrolled production of ketone bodies -> ketoacidosis

Question 3

Target Tissues/Effects of Insulin

Answer 3

Liver: glycolysis, synthetic processes - STIMULATED; GNG, glycogen breakdown - INHIBITED

Muscle: glucose uptake, synthetic processes - STIMULATED

Adipose tissue: glucose uptake, TAG synthesis - STIMULATED

Question 4

Target Tissues/Effects of Glucagon

Answer 4

Liver: gluconeogenesis, glycogen breakdown - STIMULATED

Adipose tissue: lipolysis - STIMULATED; TAG synthesis - INHIBITED

Question 5

Metabolic Effects of Type 1 Diabetes (Insulin Deficiency) - Carbohydrate

Answer 5

Increase gluconeogenesis

Increase glycogenolysis

Decrease glycogen synthesis

Decrease glucose uptake by tissues (because no insulin to ‘tell’ tissues is available)

Question 6

Metabolic Effects of Type 1 Diabetes (Insulin Deficiency) - Lipid

Answer 6

Increase hormone-sensitive lipase activity

Decrease lipid synthesis

Increase beta-oxidation of FA

Increase ketogenesis

Question 7

Metabolic Effects of Type 1 Diabetes (Insulin Deficiency) - Protein

Answer 7

Increase protein degradation

Decrease protein synthesis

Question 8

What are the physiological consequences of Type 1 Diabetes?

Answer 8

1. Blood glucose exceeds kidney resorptive capacity -> glycosuria with H₂O excretion
   - polyuria (frequent urination)
   - polydipsia (excessive thirst)
   - polyphagia (excessive hunger)
2. Glucose loss -> depletes carbohydrate stores
3. Increased TAG, protein mobilization -> wasting
4. Increase beta-oxidation -> high [acetyl coA], [ketone bodies]
5. Acetyl CoA
   - accumulates in liver because OAA -> GNG
   - converted to ketone bodies (but more than tissues can use)
   - result: ketoacidosis -> pH drops
   - consequences: dehydration + acidosis -> coma
   - acetoacetate increases -> acetone increases -> ‘acetone breath’

Question 9

Why does insulin deficiency in type 1 diabetes lead to ketoacidosis but starvation conditions do not?

Question 10

Describe hyperglycemic, hyperosmolar coma in Type 2 Diabetes

Answer 10

Hyperglycemia (worsened by failure to take insulin or hypoglycemic drugs, an infection, or a coincidental medical problem such as a heart attack) leads to urinary losses of water, glucose, and electrolytes (sodium, chloride, and potassium)

Osmotic diuresis reduces circulation blood volume -> worsens insulin resistance and hyperglycemia

Over the course of several days, becomes extremely hyperglycemic, dehydrated, and ultimately comatose

*Ketoacidosis does not develop in these patients