GLUCOSE REGULATION

• Euglycemia

  Normal blood glucose range: 70 - 99 mg/dl fasting or 100 - 140 mg/dl in 2 hour postprandial state
• Hyperglycemia

  High blood glucose: 100 mg/dl fasting or greater than 140 mg/dl 2 hour postprandial state
• Hypoglycemia

  Low blood glucose: Less than 70 mg/dl
• Maintaining glucose balance

  1. Hormone to lower glucose: Insulin

  2. Counterregulatory hormones to raise glucose: Glucagon, Cortisol
• Problems arise when hormones are deficient or excessive or when production is not balanced with the blood glucose need
• Maintaining glucose balance

  1. Proinsulin secreted by beta cells in pancreas is transformed by liver into active insulin

  2. Insulin attaches to receptors on target cells and promotes glucose transport into cells
• Pancreas cells that produce hormones


  • Alpha cells: Glucagon (stimulates breakdown of glycogen in liver, formation of carbohydrates in liver, breakdown of lipids in both liver and adipose tissue, increases blood sugar level, triggered at 70 mg/dl)
  • Beta cells: Insulin (facilitates movement of glucose across cell membranes into cells, decreasing blood glucose levels, release regulated by blood glucose)
  • Delta cells: Somatostatin (neurotransmitter that inhibits production of both glucagon and insulin)
• Diabetes mellitus


  Disorder of hyperglycemia resulting from defect in insulin secretion, insulin action, or both, leading to abnormalities in carbohydrate, protein, and fat metabolism
• Types of diabetes mellitus

  • Type 1 diabetes mellitus (T1D) "INSULIN DEFICIENCY"
  • Type 2 diabetes mellitus (T2D) "INSULIN RESISTANCE"
  • Gestational diabetes
• Type 1 diabetes mellitus (T1D)

  • Results from destruction of beta cells of islets of Langerhans in the pancreas, leading to insulin no longer being produced
  • Autoimmune destruction of islet beta cells, slowly destroys 80-90% leading to symptoms
• Etiology of type 1 diabetes

  • Most often in childhood, adolescence but can occur at any age
  • Genetic predisposition plays a role, environmental factors like viral illness trigger development
• Risk factors for type 1 diabetes

  • 1 in 400 to 1 in 1000 in general population
  • Child of person with diabetes: 1 in 20 to 1 in 50
  • Genetic markers identified
• No prevention methods for type 1 diabetes, only complication prevention
• Characteristics of type 1 diabetes

  • Hyperglycemia
  • Breakdown of body fats and proteins
  • Development of ketosis from lack of insulin to transport glucose into cells
• Polyuria


  Hyperglycemia causes serum hyperosmolarity, drawing water from intracellular spaces into general circulation, increasing blood volume and renal blood flow, hyperglycemia acts as osmotic diuretic
• Polydipsia


  Activation of thirst sensor due to decrease in intracellular volume and increased urinary output
• Polyphagia


  Glucose cannot enter cell without insulin, energy production decreases, stimulating hunger, leads to weight loss from loss of water, breakdown of proteins and fats
• Glycosuria


  Blood glucose level exceeds renal threshold (180 mg/dl)
• People with type 1 diabetes require lifelong exogenous insulin
• Short-term consequences of hyperglycemia

  • Dehydration
• Long-term consequences of hyperglycemia

  • Microvascular & macrovascular damage
  • Closely controlled blood glucose reduces risk of complications by 60%
• Diabetic retinopathy


  Changes to the retina, prevalence strongly related to duration of diabetes
• Diabetic nephropathy


  • Disease of kidneys characterized by presence of albumin in urine, hypertension, edema, progressive renal insufficiency
  • Thickening of basement membrane of glomeruli impairs renal function
  • First indication is microalbuminuria
  • Hypertension accelerates progress, requires progressive antihypertensive management
• Diabetic neuropathy


  • Disorder in peripheral nerves and autonomic nervous system
  • Thickening of walls of blood vessels that supply nerves, causing decrease in nutrients
  • Demyelination of Schwann cells that surround and insulate nerves, slowing nerve conduction
  • Leads to sexual dysfunction and cognitive dysfunction
• Macrovascular complications of hyperglycemia

  • Hypertension, hyperlipidemia, cigarette smoking and obesity increase risk
  • Cardiovascular disease, stroke, peripheral vascular disease
  • Reduced immunity from vascular changes and hyperglycemia
• Alterations in mood

  Depressive symptoms lead to lower quality of life, difficulty managing self-care, higher HbA1C, less adherence to treatment regimen
• Increased susceptibility to infection

  • Vascular, neurologic impairments lead to sensory impairments and slow healing
  • Nephrosclerosis and urinary retention predispose to pyelonephritis and urinary tract infections
• Periodontal disease

  Progresses more rapidly if diabetes is poorly controlled
• Foot complications


  • Vascular changes result in arteriosclerosis
  • Sense of touch and perception of pain are absent
  • Most common trauma is cracks, blisters, pressure, ingrown toenails
  • Foot lesion begins as superficial skin ulcer, can extend deeper and develop gangrene
  • Require podiatrist care, no pedis, no heating pads, daily foot checks, don't go barefoot
• Diabetic ketoacidosis (DKA)


  • Emergent, >300 mg/dl, may occur when energy requirements increase during physical or emotional stress
  • Involves 4 metabolic problems: hyperosmolarity, metabolic acidosis, extracellular volume depletion, electrolyte imbalances
  • Manifested by excessive thirst, flushed/warm/dry skin, Kussmaul respiration, nausea/vomiting, blurred vision, weight loss, altered level of consciousness
  • Treated with 8-10L fluid replacement, regular insulin infusions, electrolyte monitoring and replacement
• Hypoglycemia

  • Rapid onset symptoms include nervousness, irritability, vision problems, hunger, diaphoresis, anxiety, palpitations, neurological changes, seizures, unconsciousness, death
• Dawn phenomenon


  Rise in blood glucose between 4am and 8am not in response to hypoglycemia, related to increase in growth hormone
• Somogyi phenomenon


  Combination of hypoglycemia during night with rebound morning rise in blood glucose to hyperglycemic levels
• Type 2 diabetes mellitus (T2D)

  • Results from insulin resistance with a defect in compensatory insulin secretion, body does not produce enough insulin to keep blood glucose levels within normal limits
• Etiology of type 2 diabetes

  • Incidence in US has increased 33% since 2003
  • Can occur at any age, usually middle age and older
  • American Indians & Alaska Natives have greater incidence than other races/ethnicities
• Risk factors for type 2 diabetes

  • Family history of diabetes
  • Obesity/physical inactivity (excess body weight increases insulin resistance)
  • Race/ethnicity
  • History of gestational diabetes, polycystic ovary syndrome, hypertension
• Focus of care for type 2 diabetes is on maintaining blood glucose at levels as nearly normal as possible through medications, dietary management, and exercise
• Metabolic syndrome


  Simultaneous presence of metabolic factors that increase risk for type 2 diabetes: abdominal obesity, hyperglycemia, hypertension, hyperlipidemia
• Hyperosmolar hyperglycemic syndrome (HHS)

  • Emergent, occurs in people with type 2 diabetes, non-ketotic, serious and life-threatening with high mortality
  • Precipitating factors are infection and surge
• PREDIABETES diagnostic criteria

  • A1C 5.7% - 6.4%
  • Fasting blood glucose 100 -125
  • 2 hour OGTT >140 - 200