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

Polycystic ovary disease

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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