Diabetes mellitus

Diabetes mellitus
Updated: 01/21/2021
© Jun Wang, MD, PhD

General features
  • Metabolic disorder of carbohydrate
  • Very common, especially type 2
  • Caused by either deficiency of insulin secretion or resistance to Insulin
  • Type 1 diabetes: Autoimmune pancreatic β cell destruction and an absolute deficiency of insulin
  • Type 2 diabetes: Combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic β cells
  • Other causes of hyperglycemia
Key risk factors
Key pathogenesis
  • Impaired metabolism in carbohydrate
  • Subsequent multi-organ dysfunction due to hyperglycemia
Clinical presentations
  • Classic presentations: polyuria, polydipsia, polyphagia, weight loss
  • May be asymptomatic
  • Presentations of complications: ketoacidosis, ocular complications, etc
Key Laboratory findings
  • Elevated fasting glucose
  • Impaired glucose tolerance test
  • Glycated hemoglobin (HbA1c): Long term monitoring
  • Urinary albumin: in patient with diabetic nephropathy
  • Insulin levels: reduced in type I, but normal or slightly higher in type II
  • C-peptide: A fragment of proinsulin, monitor insulin production
  • Autoantibodies: type 1
  • Tests for complications: ketone, etc
Classifications
Immune mediated
Idiopathic
  • Type 2 diabetes (Insulin resistance with relative insulin deficiency or secretory defect with insulin resistance.
  • Other specific types
Genetic defects of β-cell function
Genetic defects in insulin action: Type A insulin resistance, Leprechaunism, etc
Diseases of the exocrine pancreas: Pancreatitis, trauma/pancreatectomy, etc
Endocrinopathies: Acromegaly, Cushing’s syndrome, Glucagonoma, etc.
Drug or chemical induced
Infections: Congenital rubella, cytomegalovirus and others
Uncommon forms of immune-mediated diabetes: Stiff-man syndrome, anti-insulin receptor antibodies, etc
Other genetic syndromes sometimes associated with diabetes: Down syndrome, Klinefelter syndrome, etc
Impaired glucose tolerance/prediabetes
  • Not overt diabetes yet
  • Higher risk for developing into diabetes
  • Diagnostic criteria:
A fasting plasma glucose between 100 and 125 mg/dL (“impaired fasting glucose”)
2-hour plasma glucose between 140 and 199 mg/dL following a 75-gm glucose OGTT,
AND/OR
A glycated hemoglobin (HbA1C) level between 5.7% and 6.4%
Diagnostic criteria for diabetes
  • HbA1C ≥6.5%, OR
  • Fast plasma glucose ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least eight hours OR
  • Two-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test.  The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75-gram anhydrous glucose dissolved in water. OR
  • In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L)
Acute complications
Chronic complications
  • Macrovascular diseases: Most common cause of mortality in long-standing diabetes
Myocardial infarction
Renal vascular insufficiency
Cerebrovascular accidents
Atherosclerosis and subsequent tissue ischemia
  • Microvascular diseases:
Nephropathy
Retinopathy
Neuropathy
  • Compromised immune function
Susceptibility to infections of the skin, tuberculosis, pneumonia, and pyelonephritis
  • Others: Cataract, glaucoma, etc
Pathological changes
  • Type 1: Reduction in the number and size of islets, insulitis (T-cell infiltrate)
  • Type 2: Amyloid deposition in islet
  • Fetus of diabetic women: Increase in islet number and size
  • Macrovascular: Atherosclerosis, hyaline arteriolosclerosis
  • Microangiopathy: Diffuse thickening of basement membranes
  • Diabetic nephropathy: Glomerular lesions, renal vascular lesions, principally arteriolosclerosis and pyelonephritis
  • Ocular: Retinal vasculopathy, cataract, glaucoma, and optic nerve damage  
Managements
  • Systemic approaches, depends on etiology and clinical presentations


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