Diabetes Mellitus Overview

Diabetes Mellitus

• Diabetes mellitus (DM) is a group of metabolic diseases characterized by elevated blood glucose (hyperglycemia)
• Caused by defects in insulin secretion, insulin action, or both
• Also defined as a chronic systemic disease with either insulin deficiency or reduced ability to use insulin
• Often referred to as "high sugars"

Incidence

• In 1995, there were 135 million DM patients worldwide
• 285 million in 2010, 366 million in 2011
• Projected to reach 552 million in 2030
• 80% of DM patients live in low and middle-income countries
• Prevalent in the elderly, with up to 50% of patients over 65 years old
• Approximately 183 million (50%) patients living with diabetes are undiagnosed
• 4.6 million deaths from diabetes occurred worldwide in 2011
• In April 2011, DM deaths in Ghana reached 2,752 (or 1.47% of total deaths)

Classification

• Four major classifications:
  • Type 1 (Juvenile/Insulin Dependent):
    • Affects 5-10% of people with diabetes
    • Typically diagnosed before age 30
    • Requires daily insulin treatment
    • Causes: genetic, immunologic, and environmental
  • Type 2 (Non-Insulin Dependent):
    • Affects 90-95% of people with diabetes
    • Usually diagnosed after age 40
    • Also common in certain ethnic/racial groups
    • Often referred to as stable diabetes
    • Causes: heredity, obesity, and environmental factors
  • Gestational Diabetes Mellitus (GDM):
    • Develops in up to 14% of pregnant women
    • Increases risk of hypertensive disorders
    • Typically occurs during the second half of pregnancy
    • Mothers are likely to have large babies
    • Common in women with a family history of diabetes; obesity is also a risk factor
  • DM associated with other conditions:
    • Associated with certain drugs (e.g., oral contraceptives, corticosteroids)
    • Hormonal conditions (e.g., adrenal insufficiency, Cushing's syndrome)
    • Accounts for 1-2% of all diagnosed DM cases

Pathophysiology

• In normal physiology, insulin is secreted by beta cells in the islets of Langerhans in the pancreas
• After a meal, insulin release increases, moving glucose from blood to muscle, liver, and fat cells.
• Insulin within these cells:
  • Transports and metabolizes glucose for energy
  • Stimulates glycogen storage in liver/muscle
  • Signals liver to stop glucose release
  • Enhances dietary fat storage in adipose tissue
  • Speeds up amino acid transport into cells
  • Inhibits the breakdown of stored glucose, protein, and fat
• During fasting periods, the pancreas releases basal insulin. Glucagon (pancreatic hormone) is released to stimulate liver's release of stored glucose when blood sugar is low

Type 1 DM Pathophysiology

• In type 1 DM, there's destruction of pancreatic beta cells, resulting in absolute insulin deficiency
• Potential causes: genetic, immunologic, or environmental factors (e.g., viral infections)
• Genetic susceptibility is thought to be an underlying cause
• Destruction mechanism may include autoimmune responses (antibodies targeting body tissues) or environmental factors like viruses or toxins

Type 2 DM Pathophysiology

• Type 2 DM involves insulin resistance and impaired insulin secretion
• Insulin resistance: reduced sensitivity to insulin
• Normal insulin receptors initiate glucose metabolism, but type 2 DM diminishes these intracellular reactions
• This makes insulin less effective at stimulating tissue glucose uptake and regulating liver glucose release
• Exact mechanisms are uncertain but genetic factors are a consideration
• To overcome resistance, the body increases insulin secretion to maintain normal/slightly elevated glucose levels
• If beta cells cannot keep up, blood glucose rises
• Despite impaired secretion, sufficient insulin often prevents ketogenesis which causes diabetic ketoacidosis (DKA) in type 2, but it may present as hyperglycemic hyperosmolar non-ketotic syndrome (HHNS)
• Slow progressive glucose intolerance means onset is often undetected for years

Diabetic Symptoms

• Symptoms of diabetes include:
  • Polyuria (increased urination)
  • Polydipsia (increased thirst)
  • Polyphagia (increased appetite)
  • Weight loss (body not getting glucose, uses fats/proteins)
  • Fatigue/weakness (cells lacking energy)
  • Glycosuria (excess glucose in urine)
  • Increased risk of infections (e.g., candidiasis)
  • Visual disturbances (blurred vision)
  • Paraesthesia (tingling/numbness in extremities)
  • Poor wound healing
  • Acetone breath (fruity/sweet odor) in cases of DKA
  • Type 1 specific symptoms include lethargy, stupor, and Kussmaul breathing

Risk Factors for Type 2 DM

• Race/ethnicity (African Americans, Hispanics, Native Americans, Asians, etc.)
• Obesity (BMI ≥ 27kg/m2 or ≥20% over desired body weight)
• Age ≥45 years
• Impaired fasting glucose or impaired glucose tolerance
• Hypertension (≥140/90 mmHg)
• Low HDL cholesterol (≤35 mg/dL or 0.9 mmol/L) and/or high triglycerides (≥250 mg/dL or 2.8 mmol/L)
• Family history of diabetes
• History of GDM or delivery of babies over 9 lbs

Diagnosis Investigations

• Urine chemistry - elevated glucose and ketones
• Blood chemistry - fasting blood sugar (≥ 7.0 mmol/L) or random blood sugar (≥11.1 mmol/L)
• Oral Glucose Tolerance Test (OGTT) ≥ 11.1 mmol/L
• HbA1c (glycosylated hemoglobin) - average blood glucose over ~3 months; normal: 4-8%
• BUE - annually
• Eye examination - annually

Diagnostic Criteria for Diabetes

• Symptoms of diabetes plus random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) (any time of day, regardless of last meal) or;
• Fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L) (no caloric intake for at least 8 hours) or;
• 2-hour postload glucose ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (75g anhydrous glucose dissolved in water)
• In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day

Diabetes Management

• Therapeutic goal: achieve euglycemia (normal blood glucose) without hypoglycemia, and without significantly impacting daily lifestyle
• Five components of management:
  • Nutritional management
  • Exercise
  • Monitoring (self-monitoring of blood glucose = SMBG)
  • Pharmacologic therapy
  • Education

Medications

• Two or more drug types may be used for optimal effect
• Older patients may first be treated with diet
• Types of medications to treat DM include:
• Sulphonylureas: stimulate pancreas to secrete insulin
• Biguanides: enhance insulin action on peripheral receptors; only effective with insulin
• Alpha Glucosidase Inhibitors: slow glucose absorption
• Thiazolidinediones (TZDs): enhance insulin action at receptor sites
• Non-sulfonylurea insulin secretagogues: stimulate insulin release
• Dipeptidyl Peptidase-4 (DPP-4) inhibitors: enhance incretin action to increase insulin release and decrease glucagon
• Insulin: used for type 1 diabetes, or type 2 in times of stress, surgery or infection; during pregnancy.

Insulin Types and Delivery Equipment

• Insulin types categorized by action speed and duration
• Insulin delivery methods:
  • Syringe and needle
  • Insulin pen
  • Insulin pump

Insulin Storage

• Insulin storage practices: refrigerated (except vial in use)
• Vials in use kept at room temperature (up to 4 weeks) unless temp> 86°F (~30°C) or <32°F (~0°C)