Diabetes Mellitus

1
Diabetes Mellitus

• Pathophysiology
• N280
• Fall 2004

2
Diabetes Mellitus

• A syndrome characterized by chronic hyperglycemia
  and other disturbances of carbohydrate, protein,
  and fat metabolism
• Diagnosed by clinical manifestations, fasting
  plasma glucose levels, and glucose tolerance
  tests
• Goals of therapy are to maintain euglycemia,
  avoid hypoglycemia, and prevent severe
  cardiovascular and neurologic complications

3
American Diabetes Association (ADA)

• Classifies four categories of diabetes mellitus
• Type 1 (absolute insulin deficiency)
• Type 2 (insulin resistance with an insulin
  secretory deficit)
• Other specific types
• Gestational diabetes
• Page 487, table 18-3

4
Type 1 diabetes mellitus

• Insulin dependent (IDDM)
• Impaired secretion of insulin by beta cells
• A result of autoimmune destruction of beta cells
  or loss of beta cells due to viral infection
• Abrupt onset of symptoms with a long pre-clinical
  period
• Common childhood disease, onset can be any age
  but is common around puberty

5
Type 1 diabetes mellitus

• Clinical Manifestations
• Affects the metabolism of fat, protein, and
  carbohydrates
• Acute onset of polyuria, polydipsia, and
  polyphagia with weight loss and wide fluctuations
  in blood glucose levels
• Ketoacidosis caused by increased metabolism of
  fats and proteins resulting in high levels of
  circulating ketonespH drops (metabolic
  acidosis)blow off acetone (sweet, fruity
  breath)--coma

6
Type 1 diabetes mellitus

• Evaluation and Treatment
• Presence of above symptoms combined with fasting
  and postprandial hyperglycemia
• Individual management however all require
  insulin, meal planning, and exercise
• Hemoglobin A1c to monitor effectiveness of
  treatment and prevent complications

7
Type 2 diabetes mellitus

• Non-insulin dependent diabetes (NIDDM)
• Cause unknown
• Resistance to metabolic affects of insulin in
  target cells
• Generally occurs in those over 40 yo but can
  occur in children
• Usually associated with obesity

8
Type 2 diabetes mellitus

• Risk factors
• Obesity, increased body mass index, family
  history of type 2 diabetes, member of an ethnic
  minority, puberty, female gender, and metabolic
  syndrome
• Clinical Manifestations
• Overweight, hyperlipidemia
• Onset is slow and insidious
• Pruritus, recurrent infections, visual changes
  and paresthesias

9
Type 2 diabetes mellitus

• Evaluation and Treatment
• Underdiagnosed
• Goal of treatment is euglycemia and correction of
  metabolic disorders
• Dietary measures, restricting caloric intake and
  both cholesterol and saturated fats
• Hyperglycemic oral medication
• Exercise is essential

10
Gestational Diabetes

• Glucose intolerance during pregnancy
• Risk factors
• Glycosuria, family history of diabetes, obesity,
  high maternal age, parity of 5 or more, a
  previous complicated pregnancy

11
Acute Complications of Diabetes Mellitus

• Hypoglycemia
• Related to insulin treatment
• Symptoms
• Pallor, tremor, anxiety, tachycardia,
  palpitations, diaphoresis, headache, dizziness,
  irritability, fatigue, poor judgment, confusion,
  visual disturbances, hunger, seizures, and coma
• Treatment to provide immediate replacement of
  glucose

12
Acute Complications of Diabetes Mellitus

• Diabetic Ketoacidosis (DKA)
• Deficiency of insulin and an increase in insulin
  counterregulatory hormones (catecholamines,
  cortisol, glucagon, growth hormone)
• Increased glucose production in liver, peripheral
  glucose usage decrease
• Fat is mobilized, ketogenesis is stimulated

13
Acute Complication of Diabetes Mellitus

• Hyperosmolar hyperglycemic nonketotic syndrome
• Uncommon complication of type 2 diabetes
• Poor glucose control resulting in high levels of
  serum glucose (gt500 mg/dl)
• High serum osmotic pressures lead to severe
  dehydration, low blood volume, and low perfusion
  pressures

14
Acute Complications of Diabetes Mellitus

• The Somogyi Effect
• Hypoglycemia followed by rebound hyperglycemia
• Rise in glucose related to counterregulatory
  hormones (epinephrine, GH, corticosteroids
  stimulated by hypoglycemia)
• The Dawn Phenomenon
• Early morning rise in blood glucose concentration
  with no hypoglycemia during the night
• Related to nocturnal levels of GH

15
Chronic Complications of Diabetes Mellitus

• Hyperglycemia and nonenzymatic glycosylation
• The reversible attachment of glucose to proteins,
  lipids, and nucleic acids without action of
  enzymes
• Advanced glycosylation end-products (AGE) are
  products of above binding AGEs have properties
  that may cause tissue injury or pathologic
  conditions associated with diabetes

16
Chronic Complications of Diabetes Mellitus

• Hyperglycemia and the polyol pathway
• Glucose metabolism used by tissues that do not
  require insulin for glucose transport (kidney,
  RBC, blood vessels, eye lens, and nerves)
• Glucose is converted to sorbitol, which is then
  converted to fructose which increases
  intracellular osmotic pressure and attracts water
  into cell, leading to cell injury

17
Chronic Complications of Diabetes Mellitus

• Protein Kinase C
• Extracellular enzyme activated by hyperglycemia
• Causes insulin resistance, vascular cell
  proliferation, enhanced contractility and
  increased permeability (contributing to micro and
  macrovascular, and neurologic complications of
  diabetes)

18
Chronic Complications of Diabetes Mellitus

• Diabetic neuopathies
• Common complication of diabetes
• Advanced glycosylation end-products and increased
  formation of polyols contribute to nerve
  degeneration and delayed conduction
• Microvascular disease
• Decreased tissue perfusion and hypoxia result
  from thickening of the capillary basement
  membrane, endothelial hyperplasia, thrombosis,
  and pericyte degeneration
• Diabetic retinopathy, diabetic nephropathy

19
Chronic Complications of Diabetes Mellitus

• Macrovascular disease
• More common in type 2 diabetes
• Atherosclerosis
• Coronary artery disease
• Stroke
• Peripheral vascular disease
• Infection
• Five reasons for increased risk of infection
• The senses, hypoxia, pathogens, blood supply, WBC

20
Chronic Complications of Diabetes Mellitus

• The senses
• Impaired vision (retinal changes) and impaired
  touch (neuropathy)
• Hypoxia
• Skin integrity compromised
• Glycosylated hemoglobin impedes release of oxygen
  to tissues
• Pathogens
• Increased blood sugar provides an excellent
  source of energy for some pathogens to proliferate

21
Chronic Complications of Diabetes Mellitus

• Blood supply
• Decreased blood supply due to vascular changes
  decreases the supply of WBC to affected tissues
• White cells
• Impaired function
• Abnormal chemotaxis, defective phagocytosis