PATHO - Endocrine

• Diabetes Mellitus


  Disorder of carbohydrate metabolism, characterized by high glucose levels resulting from the body's inability to produce or utilize insulin
• Types of Diabetes Mellitus

  • Type 1 DM
  • Type 2 DM
  • Gestational DM
  • Specific types of DM due to other causes
• 30.3 million Americans (9.4%) have diabetes, with increased prevalence in those aged ≥ 65 (25% are diabetic)
• Major risk factors for diabetes

  • Obesity
  • Sedentary behavior
• Hispanic, African American, American Indian and Alaskan Native populations have the highest incidences of diabetes
• Glucose Production

  1. Carbohydrates

  2. Glucose

  3. Insulin

  4. Cells
• There is a synchronous rise and fall of insulin and glucose following ingesting carbohydrates
• Glucose


  • Major energy source for cell function
  • Requires insulin to facilitate its diffusion into a cell
• Insulin


  • Hormone produced by the Beta cells of the Islets of Langerhans
  • Facilitates glucose uptake by cells
  • Enhances cellular permeability
  • Anabolic hormone that can. hypertrophy cells
• Glycogen


  • Can be stored in any cell, but most abundant in liver and muscle cells
• Glycogen metabolism

  1. Glycogenesis (formation of glycogen)

  2. Glycogenolysis (glycogen to glucose)
• Major glucose-regulating hormones


  • Insulin
  • Glucagon
  • Somatostatin
  • Incretins
  • Hormones that increase insulin secretion or glucose stimulus for insulin: Growth Hormone, Cortisol, Epinephrine, Progesterone, Estrogen
• Hyperinsulinemia


  Occurs with insulin resistance
• Glucose regulation during prolonged starvation or fasting

  1. Liver breaks down glycogen (Glycogenolysis)

  2. Glucose released from Liver and Muscle

  3. No more glycogen, fat breaks down

  4. No more fat, muscle breaks down

  5. Liver, muscle, fatty acids, glycerol, ketones, gluconeogenesis (amino acids) raise blood glucose
• Hypoglycemia


  Blood glucose < 70 mg/dL
• Hyperglycemia


  Blood glucose ≥ 200 mg/dL
• Type 1 Diabetes Mellitus


  Immune mediated destruction of beta-cells leading to absolute insulin deficiency
• Type 2 Diabetes Mellitus


  Insulin resistance with relative insulin deficiency; OR Secretory defect along with insulin resistance
• Risk factors for Type 2 Diabetes

  • Age
  • Obesity
  • Lack of physical activity
• Diagnostic criteria for Diabetes Mellitus

  • Fasting blood sugar: Pre-diabetes 100-125 mg/dL, Diabetes ≥ 126 mg/dL
  • Hemoglobin A1C: Pre-diabetes 5.7-6.4%, Diabetes ≥ 6.5%
• Type 1 Diabetes Mellitus

  • Peak onset between 11-13 years
  • Whites 1.5-2x greater incidence than others
  • Seems to have genetic factor
  • Normal weight or underweight
  • Diabetic ketoacidosis can be life-threatening
• Symptoms of Type 1 Diabetes Mellitus

  • Polydipsia
  • Polyuria
  • Polyphagia
  • Weight loss
  • Fatigue
  • Recurrent infections
  • Genital pruritus (fungal/candidal growth)
  • Blurred vision
• Type 2 Diabetes Mellitus

  • 90-95% of those with DM
  • Incidence in all age groups has doubled since 1980
  • Risk increases after age 40
  • High in many traditionally hunter/gatherer groups (Native American/American Indian/First Nations)
  • "Diabesity" - obesity, diabetes, chronic inflammatory processes
• Metabolic Syndrome


  Three or more of the following:

  Waist circumference > 40 inches (M), 35 inches (F)

  Triglycerides > 150 mg/dL

  HDL cholesterol < 40 mg/dL (M), < 50 mg/dL (F)

  Blood pressure > 130/85 mmHg

  Fasting glucose > 100 mg/dL
• Metabolic Syndrome increases risk of cardiovascular disease
• Gestational Diabetes


  • Affects 4% of pregnant women
  • Increases in hormones (especially estrogen) increase insulin resistance
  • Elevated glucose crosses the placenta, but elevated insulin does not
  • May lead to large-for-gestational-age neonates who are born with excessive insulin, hypoglycemia, and risk for obesity
• Maternal risk factors for Gestational Diabetes Mellitus

  • Hypertension
  • Obesity (BMI >30)
  • History of GDM in a previous pregnancy
  • Strong family history of DM
  • Urine + for glucose at prenatal visit
  • Previous big baby (9 lbs)
  • Unexplained still birth in past
  • Previous delivery of infant with birth defect
• Many women who develop GDM don't have any risk factors
• Acute Complications of Diabetes Mellitus

  • Hypoglycemia
  • Diabetic ketoacidosis (DKA)
  • Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)
• Hypoglycemia


  • Blood glucose < 70 mg/dL
  • Signs and symptoms include sweating, hunger, dizziness, nervousness, tremulousness, irritability, headache, heart palpitations, confusion, disorientation, inability to concentrate, seizures, stupor or loss of consciousness
  • Cellular hypoglycemia deprives cells of their energy source, can lead to coma and death if not restored
• Diabetic Ketoacidosis (DKA)


  • Serum glucose > 250 mg/dL
  • serum bicarbonate < 18 mmol/dL
  • serum pH < 7.30
  • presence of an anion gap
  • presence of urine and serum ketones
  • Dysfunctional pancreas, no glucose uptake in cells, liver and muscle break down fatty acids and amino acids to produce ketones, increasing glucose and ketones in blood
• Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS)

  • Serum glucose > 600 mg/dL
  • serum pH > 7.30
  • serum bicarbonate > 15 mmol/L
  • serum osmolality > 320 mOsm/L
  • absence (or very small amount) of ketones
  • Pancreas increases insulin, but cells resist insulin, leading to very high blood glucose
• Long-term complications of diabetes

  • Vascular (accelerated atherosclerosis, CAD, CVA, PAD, retinopathy, nephropathy)
  • Endothelial activation and injury (small vessels)
  • Microalbuminuria progressing to end-stage renal disease
  • Neuropathies
  • Impaired immunity and wound healing
  • Reproductive (vaginitis, balanitis, GDM)
  • Psychological (anxiety, depression, eating disorder)
• Endocrine Signaling

  • When the endocrine system dysfunctions, there is an imbalance of hormones that can cause hyperfunction or hypofunction of the target organ
  • Dysfunction can occur at the hypothalamus, the pituitary, or with the individual endocrine gland itself
• Regulation of hormone release

  • Chemical factors (blood glucose, calcium level)
  • Endocrine factors (endocrine gland controlling another)
  • Neural control
• Pituitary


  • Pea sized gland deep in brain that serves as the coordinating center for the endocrine system
  • Anterior pituitary (adenohypophysis)
  • Posterior pituitary (neurohypophysis)
• Types of endocrine conditions

  • Hormone deficiency
  • Hormone excess
  • Hormone resistance
• Primary endocrine dysfunction

  Dysfunction caused by the endocrine gland itself
• Secondary endocrine dysfunction

  Dysfunction caused by abnormal pituitary activity
• Tertiary endocrine dysfunction

  Dysfunction caused by hypothalamic origin