Assessing Glucose Metabolism Disorders

Assessing Laboratory Tests for Glucose Metabolism Disorders

• Glucose is a vital energy source for tissues and organs
• Sources include diet, glycogen breakdown, and gluconeogenesis (mostly in the liver, less in the kidneys)
• Triglycerides (from diet or storage) which includes fatty acids and glycerol
• Ketones (acetoacetate, hydroxybutyrate, and acetone) play a role in glucose metabolism disorders

The Pancreas

• Composed of two parts: exocrine and endocrine pancreas
• Alpha cells, beta cells, and delta cells regulate blood glucose levels

Major Sources of Fuel for Metabolism

• Glucose is a vital energy source for the body
• Fuel sources include diet, stored glycogen, and newly synthesized glucose (gluconeogenesis)
• Triglycerides, broken down into fatty acids and glycerol, serve as energy reserves
• Ketones are also energy sources, and are important in glucose metabolism disorders

Glucose – A Major Energy Source

• Glucose is the primary energy substrate for some tissues
• The body's glucose supply comes from dietary intake and endogenous production (glycogenolysis and gluconeogenesis)
• All energy production starts with glycolysis
• Many tissues fully oxidize glucose to carbon dioxide
• Other tissues metabolize glucose to lactate which is converted to glucose in the liver and kidneys (gluconeogenesis)

Glucose Homeostasis

• Glucose homeostasis maintains balance in blood glucose levels
• Excess glucose is stored as glycogen in the liver and muscles. Also converted into triglycerides stored in adipose tissue
• If glucose is low, glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose) occur in the liver

Key Metabolic Processes

• Excess Glucose:
  • Glycolysis produces pyruvate from glucose
  • Excess carbohydrates and fat are converted to triglycerides for storage
• Shortage of Glucose:
  • Gluconeogenesis generates glucose from non-carbohydrate sources
  • Glycogenolysis breaks down glycogen to glucose
  • Lipolysis liberates fatty acids from stored triglycerides
  • Ketogenesis forms ketones, important energy sources when glucose is low.
  • Beta-oxidation of fatty acids further produces acetyl-CoA for ketogenesis

Regulation of Blood Glucose Concentration

• Fed State:
  • High dietary glucose/amino acid intake leads to increased insulin
  • The liver, muscles, and adipose tissue take up glucose and store it as glycogen or triglycerides.
• Fasting State:
  • Increased glucagon, adrenaline, glucocorticoids, and growth hormones
  • This stimulates glycogenolysis and gluconeogenesis in the liver and muscle, and lipolysis in adipose tissue, which increases blood glucose

The Actions of Insulin

• Insulin stimulates several processes:
  • Glucose uptake into muscle and adipose tissue
  • Glycogen synthesis
  • Protein synthesis

Disorders of Glucose Metabolism - Diabetes Mellitus

• Type 1: Absolute insulin deficiency, autoimmune destruction of beta cells and prone to ketosis
• Type 2: Relative insulin deficiency, insulin resistance, and usually associated with obesity and other factors.

Clinical Features of Diabetes Mellitus types 1 and 2

• Diagnosis of Diabetes Mellitus involves age, weight, onset, ketosis, endogenous insulin, islet cell antibodies, and HLA associations.

Signs and Symptoms of Diabetes Mellitus (Diagnosis)

• Symptoms at Diagnosis are often indicative of crisis involving polyuria, thirst, and extreme weakness/fatigue.

Disorders of Glucose Metabolism - Other types

• Secondary diabetes (from pancreatic/endocrine diseases/drug therapy)
• Gestational diabetes is carbohydrate intolerance during pregnancy, with high risk of DM type 2

Types of Diabetes and Their Characteristics

• Table summarizing different types of diabetes: Type 1, type 2, Gestational

Diagnosis of Diabetes Mellitus

• Diagnosis methods include venous plasma glucose (fasting and random glucose), oral glucose tolerance test, and glycated hemoglobin (HbA1c) combined with symptoms.

Clinical practice Guidelines for Diabetes Diagnosis (Diabetes Canada)

• Standards for diagnosing diabetes include fasting plasma glucose (FPG), random plasma glucose, oral glucose tolerance test, and HbA1c.
• If classic symptoms accompany plasma glucose levels ≥11.1 mmol/L (200 mg/dL), the diagnosis is diabetes

Monitoring of Diabetes Mellitus

• HbA1c is important in monitoring glycemic control
• Self-monitoring of blood glucose (SMBG) using point-of-care glucose meters
• Continuous glucose monitoring is advised for some individuals

Diabetic Ketoacidosis (DKA)

• A complication of diabetes, type 1 in particular, caused by a lack of insulin, infection, trauma, leading to high glucose, ketone buildup, and ketoacidosis (metabolic acidosis).
• Symptoms often include elevated glucose, glycosuria (glucose in urine), and extremely high ketones.

Diabetic Ketoacidosis- Development

• Glucose increases, causing osmotic diuresis and dehydration
• Increased lipolysis leads to fatty acid overproduction.
• Conversion to ketones causes metabolic acidosis, often accompanied by fruity/acetone breath odor.

Treatment of Diabetic Ketoacidosis

• Close clinical and biochemical monitoring
• Fluid replacement to restore ECF and balance blood pressure and glomerular function
• Insulin to restore glucose utilization and metabolism
• Potassium monitoring and potentially replacement to address whole body potassium depletion

Diabetic Ketoacidosis- Laboratory

• Glucose levels are monitored hourly, until levels are reduced to less than 14 mmol/L
• Ketone and electrolyte measurements and blood gas analysis are important

Hyperosmolar Hyperglycemic State (HHS)

• A complication of type 2 diabetes involving extreme hyperglycemia (often exceeding 50 mmol/L), osmotic diuresis and dehydration without ketosis. It is a more serious complication associated with elderly patients who are often not eating or drinking reducing insulin availability, and increased stress

Hyperosmolar Hyperglycemia State - Treatment

• Treatment is similar to DKA, emphasizing fluid replacement and, if needed, insulin in small doses.
• Potassium levels must be closely monitored.

DKA vs HHS

• Comparison of diabetic ketoacidosis and hyperosmolar hyperglycaemic state based on symptoms and characteristics, including type of diabetes, plasma glucose, ketone presence, acidosis, dehydration, and hyperventilation

Hypoglycemia

• Low blood glucose (< 2.5 mmol/L), can be either fasting or reactive
• Clinical effects of hypoglycemia can lead to symptoms such as shaky/increasing heartbeat, heavy breathing, stimulation of other hormones, confusion/loss of consciousness

Hypoglycemia - Assessment

• Whipple's triad (symptoms, laboratory confirmation, relief with glucose) is used for diagnosis
• Insulin is analyzed during symptomatic episodes

Hypoglycemia - Causes

• Many possible causes including insulinoma, malignancy, hepatic/renal disease, decreased gluconeogenesis, Addison's disease, sepsis. Or from factors like excessive/improper insulin, drug-induced, low-carbohydrate intake, strenuous exercise, and alcohol.