Diabetes

• • Exercise 
  • Reaction opposite of fasting 
  • ↑ glucose uptake & utilization by muscles cells
  • Regular exercise stimulates 

  1. Up-regulation of insulin independent GLUT4 transporters in skeletal muscle cell membranes
  2. Up-regulation of insulin receptors in skeletal muscle cell membranes
• • Diabetes mellitus v diabetes insipidus
  • Diabetes – “running through”
  • Diuresis: large flow of water
  • Mellitus – “sweet”
  • Osmotic diuresis
  • Solute loss (glucose) w/ accompanying water loss
  • Glucosuria: glucose in the urine
  • ≈ 180 mg/dL whole blood: renal threshold for some nephrons
  • ≈ 300 mg/dL whole blood: renal threshold for all nephrons
  • Cause: lack of insulin or functional insulin receptors
  • Insipidus – “non-sweet”
  • Water diuresis
  • Solvent loss w/o accompanying solute loss:
  • Cause: lack of vasopressin or functional vasopressin receptors
  • Central diabetes insipidus
  • Nephrogenic diabetes insipidus
• • Diabetes testing
  • Blood glucose tests 
  • Fasting – 8 hours
  • Expected glucose concentrations
  • Expected insulin?
  • Oral glucose tolerance test
  • Test ability to respond to glucose
  • Fasting – 8 hours
  • Drink glucose solution
• Type I diabetes mellitus, also known as insulin dependent diabetes or juvenile diabetes, is a condition where the individual lacks the ability to produce insulin due to autoimmune destruction of β cells.
• Type I diabetes mellitus results in low plasma insulin levels and high plasma glucose levels, leading to an inability to absorb glucose.
• Tonic activity of glucagon is a characteristic feature of Type I diabetes mellitus.
• Continued liver glycogenolysis and gluconeogenesis are common in Type I diabetes mellitus.
• • Diabetes mellitus pathophysiology
  • Dehydration
  • Glucosuria
  • Polyuria
  • ↓ blood volume 
  • ↓ blood pressure
  • ↑ plasma osmolarity
  • Polydipsia
  • Metabolic acidosis
  • Ketone production
  • Circulatory failure requires a switch to anaerobic metabolism: produces additional metabolic acids
• Continued lipolysis and protein breakdown are also common in Type I diabetes mellitus.
• Osmotic diuresis is a common occurrence in Type I diabetes mellitus.
• Glucose transport maximum (Tmax) is a key concept in Type I diabetes mellitus.
• If the filtered load is greater than the Tmax, the substance will be present in the urine.
• • Diabetes mellitus pathophysiology
  • Tissue loss
  • Continued catabolism
  • Augments hyperglycemia
  • Polyphagia
  • No insulin signal to satiety center
  • ↑ appetite 
• Glucosuria, defined as plasma [glucose] ≈ 180 mg/dL, is a common occurrence in Type I diabetes mellitus.
• Water follows the solute in Type I diabetes mellitus.
• Diabetic ketoacidosis is a complication of Type I diabetes mellitus, characterized by ↑ lipolysis, ↑ plasma ketones, and ↑ ketones in urine, leading to ↑ H+ in plasma.
• Other problems associated with Type I diabetes mellitus include ↑ Na+ loss and additional water loss, ↓ plasma volume, ↓ arterial pressure, and ↓ blood flow.
• The number of glucose transporters in skeletal muscle cells is unknown.
• Type II diabetes mellitus: non-insulin dependent diabetes (adult onset)
• Decreased sensitivity to insulin
• Often normal or elevated plasma insulin levels – may progress to reduced insulin
• High plasma glucose levels
• Resistin hormone is produced in response to excess adipose tissue and is involved in inflammation.
• Treatment for insulin resistance includes diet and weight reduction, and exercise.
• Down-regulation of glucose transporters in skeletal muscle and adipose tissue is a factor in insulin resistance.
• Defective β pancreatic cells do not increase insulin secretion at high plasma glucose levels.
• Inability to absorb glucose
• Continued liver glycogenolysis & gluconeogenesis
• Continued lipolysis
• • Hypoglycemia: low plasma glucose concentration
  • Usually in fasted-state
  • Potential causes
  • Excess insulin
  • Β cell tumor
  • Excess insulin injection
  • ↑ insulin secretion (sulfonylureas for type 2 diabetes mellitus treatment)
  • Poor fasted-state regulation
  • Liver disease
  • Inactive α cells & ↓ glucagon secretion
  • ↓ glycogenolysis, gluconeogenesis
  • ↓ cortisol 
  • Symptoms
  • Sympathetic system responses
  • Nervousness, ↑ heart rate, sweating, anxiety
  • Lack of glucose to brain
  • Headache, confusion, dizziness, lack of coordination
  • Convulsions, unconsciousness, & coma 
• Role of obesity
• Insulin resistance