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
History of impaired glucose tolerance,
gestational diabetes, etc
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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of endocrine pancreas
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of endocrine system
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