Physiology
Normal Sate
Normoglycemia
-
Definition: Normal blood glucose levels
-
Fasting: 70-99 mg/dL (3.9-5.5 mmol/L)
-
Postprandial (2 hours after eating): < 140 mg/dL (7.8 mmol/L)
-
Maintenance: A complex interplay of hormones (insulin, glucagon, epinephrine, cortisol), liver function, and cellular glucose uptake maintains normoglycemia
-
Importance: Provides a constant supply of glucose for energy, especially for the brain, which relies heavily on glucose
Abnormal States
Hyperglycemia
-
Definition: Abnormally high blood glucose levels
-
Causes:
-
Diabetes Mellitus (Type 1 and Type 2):
-
Type 1: Autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency
-
Type 2: Insulin resistance (cells don’t respond properly to insulin) and relative insulin deficiency (pancreas can’t produce enough insulin to overcome resistance)
-
Gestational Diabetes: Insulin resistance during pregnancy
-
Other Endocrine Disorders: Cushing’s syndrome (excess cortisol), acromegaly (excess growth hormone), hyperthyroidism
-
Pancreatic Diseases: Pancreatitis, cystic fibrosis (affecting pancreatic function)
-
Medications: Corticosteroids, some diuretics
-
Stress/Illness: Stress hormones (cortisol, epinephrine) can raise blood glucose
-
Symptoms:
-
Classic Symptoms: Polyuria (frequent urination), polydipsia (excessive thirst), polyphagia (increased hunger), unexplained weight loss
-
Other Symptoms: Fatigue, blurred vision, slow-healing sores, frequent infections
-
Complications:
-
Acute:
-
Diabetic Ketoacidosis (DKA): Primarily in Type 1 diabetes. Insulin deficiency leads to increased lipolysis, ketone body production, and metabolic acidosis
-
Hyperosmolar Hyperglycemic State (HHS): Primarily in Type 2 diabetes. Severe hyperglycemia leads to dehydration and hyperosmolarity, but less ketosis than DKA
-
Chronic:
-
Microvascular Complications:
-
Retinopathy: Damage to blood vessels in the retina, leading to vision loss
-
Nephropathy: Damage to blood vessels in the kidneys, leading to kidney failure
-
Neuropathy: Damage to nerves, leading to pain, numbness, and loss of sensation
-
Macrovascular Complications:
-
Cardiovascular Disease: Increased risk of heart attacks and strokes
-
Peripheral Artery Disease: Reduced blood flow to the limbs, increasing the risk of amputation
Hypoglycemia
-
Definition: Abnormally low blood glucose levels
-
Threshold: Generally defined as < 70 mg/dL (3.9 mmol/L), but symptoms can vary
-
Causes:
-
Excess Insulin:
-
Insulin Overdose: In diabetic patients
-
Insulinoma: Insulin-secreting tumor of the pancreas
-
Reactive Hypoglycemia: Exaggerated insulin release after a meal
-
Fasting Hypoglycemia:
-
Liver Disease: Impaired gluconeogenesis and glycogen storage
-
Kidney Disease: Impaired gluconeogenesis
-
Hormone Deficiencies: Adrenal insufficiency (low cortisol), growth hormone deficiency
-
Certain Tumors: Non-islet cell tumors can secrete insulin-like substances
-
Alcohol Consumption: Inhibits gluconeogenesis
-
Intense Exercise: Can deplete glycogen stores
-
Symptoms:
-
Adrenergic Symptoms (Early): Sweating, shakiness, anxiety, palpitations, hunger
-
Neuroglycopenic Symptoms (Later): Confusion, dizziness, blurred vision, difficulty speaking, seizures, loss of consciousness
-
Complications:
-
Brain Damage: Prolonged or severe hypoglycemia can lead to irreversible brain damage
- Seizures
- Coma
- Death
Insulin Resistance
-
Definition: Cells don’t respond normally to insulin, requiring higher levels of insulin to achieve the same effect on glucose uptake
-
Causes:
-
Obesity: Excess adipose tissue releases factors that interfere with insulin signaling
-
Genetics: Some individuals are genetically predisposed to insulin resistance
- Physical Inactivity
- Inflammation
- Aging
-
Consequences:
-
Hyperinsulinemia: Elevated insulin levels as the pancreas tries to compensate for resistance
-
Prediabetes: Impaired fasting glucose or impaired glucose tolerance
-
Type 2 Diabetes: Eventually, the pancreas may not be able to produce enough insulin to overcome resistance
-
Metabolic Syndrome: A cluster of conditions including insulin resistance, abdominal obesity, high blood pressure, high triglycerides, and low HDL cholesterol, increasing the risk of cardiovascular disease and type 2 diabetes
Key Terms
-
Normoglycemia: Normal blood glucose levels
-
Hyperglycemia: Elevated blood glucose levels
-
Hypoglycemia: Reduced blood glucose levels
-
Insulin Resistance: Impaired cellular response to insulin
-
Glycogen Storage Diseases (GSDs): Genetic defects in glycogen metabolism
-
Galactosemia: Impaired galactose metabolism
-
Fructose Intolerance: Impaired fructose metabolism
-
Pentosuria: Excess excretion of pentoses in the urine