Diabetes mellitus, type 2

Diabetes mellitus, type 2 

Updated: 01/21/2021

© Jun Wang, MD, PhD

General features
  • Complex etiology
  • Much more common than type 1 diabetes
  • Not absolutely dependent on insulin
  • Onset most often in adults
  • Fungal infection due to impaired lymphocytic function
  • Commonly associated with chronic macrovascular, microvascular and neuropathic complications
Key risk factors
  • Genetics
Susceptible genotype
Family history of type 2 diabetes in a first degree relative
  • Possible risk factors
Obesity
Hypertension/dyslipidemia
Lower birth weight
Environmental pullutants
Insulin resistance and metabolic syndrome
Others: immunization, diet, etc
Key pathogenesis
  • Combination of insulin resistance, relatively inadequate insulin secretion, and excessive or inappropriate glucagon secretion
  • Obesity associated elevated free fatty acid and glucose eventually result in beta cell failure
  • Impaired metabolism in carbohydrate
  • Subsequent multi-organ dysfunction due to hyperglycemia
Insulin resistance
  • Less-than-expected biological effect by a given amount of insulin
Failure to inhibit gluconeogenesis, resulting high fasting blood glucose levels
Failure of glucose uptake and glycogen synthesis following a meal, resulting high post-prandial blood glucose level
Failure to inhibit activation of "hormone-sensitive" lipase, leading to excess triglyceride breakdown in adipocytes and excess circulating free fatty acids (FFAs)
  • Associated with reduced insulin receptor quantity or receptor signaling pathway defects
  • May be caused by free fatty acid, adipokines, inflammation
  • Associated with various endocrine, metabolic, and genetic conditions
  • Present with obesity, glucose intolerance, diabetes, and the metabolic syndrome, as well as an extreme insulin-resistant state
Metabolic syndrome
  • Insulin resistance accompanying abnormal adipose metabolism
  • Risk factor for type 2 diabetes
  • Definition by National Cholesterol Education Program Adult Treatment Panel III, 3 of the below
Glucose ≥5.6 mmol/L (100 mg/dL) or drug treatment for elevated blood glucose
HDL: <1.0 mmol/L (40 mg/dL) (men); <1.3 mmol/L (50 mg/dL) (women) or drug treatment for low HDL-C
Tryglycerides: ≥1.7 mmol/L (150 mg/dL) or drug treatment for elevated triglycerides
Hypertension: ≥130/85 mmHg or drug treatment for hypertension
Obesity: Waist ≥102 cm (men) or ≥88 cm (women)
Beta cell failure
  • Occurs prior to diabetes
  • Reduced quantity due to increased apoptosis caused by various hormones or growth factors
  • Functional defects due to abnormal incretin effect, prolonged hyperglycemia and elevated levels of free fatty acid, amyloid or certain genetic factors affecting insulin secretion
Clinical presentations
  • Classic presentations: polyuria, polydipsia, polyphagia, weight loss
  • Presentations of complications: Hyperosmolar hyperosmotic syndrome, etc
  • Non specific presentations: fatigue, nausea, blurred vision, lower-extremity paresthesia
  • Fungal infection
Key Laboratory findings
  • Elevated fasting glucose
  • Impaired glucose tolerance
  • Glycated hemoglobin (HbA1c): Long term monitoring
  • Urinary albumin: in patient with diabetic nephropathy
  • Normal or elevated Insulin levels
  • Normal or elevated level of C-peptide
  • Tests for complications: osmolality, etc
  • NO autoantibodies
Pathological changes
  • Amyloid deposit in islet

Type 2 versus Type 1


Managements
  • Systemic approaches
  • Glycemic control and monitoring
  • Balanced nutrition, exercise, smoke cessation
  • Immunizations
  • Psychosocial support
  • Pharmacologic therapy: Biguanides, sulfonylureas, etc
  • Managements of complications



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