Wk 9&10 Lecture 5: Diabetes and Keton Bodies

Introduction to Diabetes and its Biochemistry

• Focus on the biochemistry of diabetes and its pathological consequences.

  • Discussion of ketone body formation and metabolism.

  • Importance of understanding metabolism, signal transduction, and hormone actions (epinephrine, glucagon, insulin).

  • Connection between metabolic issues and diabetic symptoms.

Case Study: Adeel's Symptoms

• Adeel is 21 and struggles with studying due to lack of energy.

• Observations of Adeel:

  • Drinks excessively (water and cola).

  • Frequent urination (suggestive of polyuria).

  • Appears thinner, likely linked to weight loss.

• Attempts to convince him to visit a physician are met with resistance.

Scene: Coffee Shop Incident

• Adeel hurriedly enters with donuts and a sugary cappuccino.

• Displays a fruity breath odor and quickly consumes food, indicating potential hypoglycemia.

• Suddenly collapses and vomits, showing signs of severe distress.

• Emergency medical assistance is summoned; rapid transport to the hospital ensues.

Hospital Arrival and Immediate Findings

• In the emergency room, Adeel is unconscious but breathing.

  • Vital signs measured showing hypotension (90/60 mmHg vs normal 120/80).

• Urinalysis shows:

  • High glucose content (glucosuria).

  • Presence of ketone bodies.

• Other symptoms: fever and signs of dehydration.

Blood Analysis Results

• Serum glucose levels are excessively high (7-11 times normal): condition termed hyperglycemia.

• Ketone bodies are present at dangerous levels (15-75 times normal).

• Adeel is in a state of ketoacidosis (low blood pH).

• Elevated potassium levels noted (hyperkalemia).

Treatment Administered

• ER resident administers intravenous bicarbonate and an intramuscular insulin injection.

• Two hours post-treatment:

  • Higher arterial blood pH achieved.

  • Blood glucose levels significantly reduced.

  • Adeel gradually regains consciousness.

Understanding Adeel's Symptoms and Signs

• Symptoms include:

  • Lack of energy, fever, and excessive thirst (polydipsia).

  • Frequent urination (polyuria).

• Signs from analysis include:

  • Unconsciousness, deep breathing, hypotension.

  • Elevated ketone and glucose levels; acidosis.

Diabetes Overview

• Diabetes prevalence in Canada (1 in 30); approximate 1 million Canadians affected.

  • Type 1 Diabetes:

    • Common in younger individuals (often under 20).

    • Autoimmune attack on insulin-producing beta cells in pancreas—leading to absolute insulin deficiency.

  • Type 2 Diabetes:

    • Typically develops in older adults, increasingly noted in younger populations.

    • Associated with obesity and often linked to lifestyle factors (poor diet, inactivity).

Hormonal Mechanisms Involved

• Insulin:

  • Peptide hormone produced by pancreatic beta cells; its release is triggered by high blood glucose.

  • Normal mechanisms involve:

    • Regulation of glucose uptake (via GLUT4).

    • Activation of glycogen synthesis and inhibition of glycogenolysis in liver/muscle.

  • Insulin also promotes fatty acid synthesis and inhibits fat mobilization.

Metabolism Without Insulin

• Without insulin, glucose uptake in muscle and fat cells decreases, leading to hyperglycemia.

• Increased fat mobilization occurs due to lack of counterbalancing effects of insulin, promoting fatty acid oxidation.

• Excess acetyl CoA levels result in increased ketone body formation, leading to ketoacidosis and further metabolic complications.

Complications of Ketoacidosis

• Elevated ketone bodies cause a drop in blood pH, resulting in acidosis.

• Adeel demonstrates deep rapid breathing to try to balance pH, which inadvertently worsens his acidosis by exhaling CO2.

• Imbalance leads to further compounding of blood acidity and can result in loss of consciousness.

Osmotic Effects and Dehydration

• Elevated glucose and ketone concentrations create a hypertonic environment in blood.

  • Causes osmotic loss of water from cells, leading to dehydration.

  • Results in excessive urination and compensatory thirst response (polydipsia).

• Hypotension resulting from significant fluid loss is dangerous and contributes to Adeel's loss of consciousness.

Conclusion and Management

• Insulin therapy effectively manages Adeel's conditions, reversing metabolic disturbances and restoring balance.

• Continuous insulin regulation is critical to prevent recurrence of hyperglycemia and associated complications.

• Importance of monitoring carbohydrate intake and insulin dosage is emphasized to prevent further episodes of hypoglycemia.