Mind map

Diabetes mellitus

Eman Elkhatib English

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Diabetes mellitus

Types
- Type 1
  - Insulin-dependent Juvenile-onset
- Type 2
  - Non-insulin-dependent Adult-onset
- Other
  - Gestational
    - Impaired glucose tolerance during pregnancy
  - LADA (Latent Autoimmune Diabetes of Adulthood)
  - MODY (maturity onset diabetes of the young)
  - Secondary
Etiology
- Type 1 DM
  - Autoimmune destruction of pancreatic β cells in genetically susceptible individuals
  - Associated with
    - HLA-DR3 and HLA-DR4
    - Other autoimmune conditions
- Type 2 DM
  - Peripheral insulin resistance and pancreatic beta cell dysfunction
  - Hereditary and environmental factors
  - Associated with
    - Metabolic syndrome
    - Risk factors
      - Positive family history / Race/ethnicity (high risk factor) / Physical inactivity / History of cardiovascular disease / Polycystic ovary syndrome / Conditions associated with insulin resistance: e.g., severe obesity and high-calorie diet / Hypertension / Dyslipidemia / History of gestational diabetes
Pathophysiology
- Insulin (normal physiology)
  - Synthesized in the β cells of the islets of Langerhans
    - Cleavage of proinsulin produces C-peptide and insulin
  - Anabolic hormone
- Type 1 DM
  - Genetic susceptibility and environmental triggers
    - Autoimmune response with production of autoantibodies
      - Progressive destruction of β cells in the pancreatic islets
        Absolute insulin deficiency
        Decreased glucose uptake in the tissues
- Type 2 DM
  - Peripheral insulin resistance
    - Central obesity
      - Increased plasma levels of free fatty acids
        Impaired insulin-dependent glucose uptake into hepatocytes, myocytes, and adipocytes
    - Increased serine kinase activity in fat and skeletal muscle cells
      - Phosphorylation of insulin receptor substrate (IRS)-1
        Decreased affinity of IRS-1 for PI3K
        Decreased expression of GLUT4 channels
        Decreased cellular glucose uptake
  - Pancreatic β cell dysfunction
    - Accumulation of pro-amylin (islet amyloid polypeptide) in the pancreas
      - Decreased endogenous insulin production
Clinical features
- Onset
  - Type 1
    - Sudden / Diabetic ketoacidosis (DKA) is the first manifestation
  - Type 2
    - Typically gradual / Majority of patients are asymptomatic. / Some may present with a hyperglycemic crisis
- Signs and symptoms
  - Symptoms of hyperglycemia
    - Polyuria
    - Polydipsia
    - Polyphagia
  - Nonspecific symptoms
    - Unexplained weight loss / Visual disturbances / Fatigue / Pruritus / Poor wound healing / Increased susceptibility to infections / Calf cramps
  - Thin appearance in type 1
  - Cutaneous signs of insulin resistance in type 2
    - Benign acanthosis nigricans Acrochordons
Complications
- Acute
  - Hyperglycemia crisis
    - Hyperosmolar hyperglycemic crisis
    - Diabetic ketoacidosis (DKA)
  - Life threatening hypoglycemia
    - inappropriate insulin therapy
    - Hypoglycemia-associated autonomic failure
      - Defective glucose counterregulation
      - Hypoglycemia unawareness
- Chronic
  - Macrovascular
    - Cerebrovascular disease
    - Coronary artery disease
    - Peripheral artery disease
  - Microvascular
    - Diabetic retinopathy
    - Diabetic nephropathy
    - Diabetic neuropathy
Diagnosis
- Hyperglycemia tests
  - Random blood glucose
  - Fasting plasma glucose
  - Oral glucose tolerance test
  - Hemoglobin A1C (HbA1c)
- Routine studies
  - BMP
    - Renal function
    - Electrolytes, including potassium
  - LIver function tests
  - Lipid panel
  - Urinary albumin-to-creatinine ratio
- Additional studies
  - C-peptide
  - Urinalaysis
    - Glucosuria
    - Ketone bodies
    - Microalbuminuria
  - Antibody testing
    - Antiglutamic acid decarboxylase antibodies (Anti-GAD)
    - Anti-tyrosine phosphatase-related islet antigen 2 (IA-2)
    - Islet cell antibody (ICA)
Management
- Lifestyle modifications
  - Regular physical activity / Balanced diet / Weight management / Smoking cessation / Limit alcohol consumption
- Type 1 DM
  - Insulin replacement therapy
    - Multiple daily injections or insulin pump
- Type 2 DM
  - Metformin
    - First-line drug of choice
  - Saxagliptin
    - Avoid in heart failure
    - Dipeptidyl peptidase-4 inhibitor
  - Empagliflozin
    - SGLT-2 inhibitors
  - Semaglutide
    - GLP-1 receptor agonists
  - Glimepiride
    - Sulfonylurea
    - Increases risk for hypoglycemia
  - Pioglitazone
    - Thiazolidinedione
    - Avoid in patients with congestive heart failure.
  - Insulin therapy