Definition of Diabetes Mellitus
Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. 1, 2
Core Pathophysiologic Features
The fundamental abnormality in diabetes is deficient insulin action on target tissues, which stems from:
- Inadequate insulin secretion from pancreatic β-cells 1
- Diminished tissue responses to insulin (insulin resistance) at one or more points in hormone action pathways 1
- Combined defects where impairment of insulin secretion and insulin action frequently coexist in the same patient 1
The basis of abnormalities in carbohydrate, fat, and protein metabolism in diabetes is this deficient insulin action on target tissues. 1
Clinical Manifestations
Acute Symptoms
Classic symptoms of marked hyperglycemia include:
- Polyuria (excessive urination) 1, 3
- Polydipsia (excessive thirst) 1, 3
- Weight loss, sometimes with polyphagia (excessive hunger) 1, 3
- Blurred vision 1
- Impairment of growth and susceptibility to certain infections may accompany chronic hyperglycemia 1
Life-Threatening Acute Complications
These represent acute, life-threatening consequences of uncontrolled diabetes that require immediate medical attention. 1, 3
Long-Term Organ Damage
The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, particularly:
Microvascular Complications
- Retinopathy with potential loss of vision 1, 2
- Nephropathy leading to renal failure 1, 2
- Peripheral neuropathy with risk of foot ulcers, amputations, and Charcot joints 1
- Autonomic neuropathy causing gastrointestinal, genitourinary, and cardiovascular symptoms and sexual dysfunction 1
Macrovascular Complications
- Atherosclerotic cardiovascular disease 1, 2
- Peripheral arterial disease 1, 2
- Cerebrovascular disease (stroke) 1, 2
Hypertension and abnormalities of lipoprotein metabolism are often found in people with diabetes. 1
Diagnostic Criteria
According to the American Diabetes Association, diabetes is diagnosed when: 2
- Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) on two occasions 1, 2
- 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test 1, 2
- HbA1c ≥6.5% 2
- Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia 2
The World Health Organization and European guidelines recommend using oral glucose tolerance testing for early detection, as it provides both fasting and 2-hour post-load glucose values, which is particularly important for detecting asymptomatic type 2 diabetes. 1
Major Etiologic Types
Type 1 Diabetes
- Characterized by autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency 1, 2
- Accounts for only 5-10% of all diabetes cases 1
- Always requires insulin treatment for survival 1, 3, 2
- Typically occurs in young subjects but may occur at any age 1
Type 2 Diabetes
- Most prevalent form (90% of all diabetes cases) comprising the majority of diabetes 1, 2
- Characterized by insulin resistance combined with progressive insulin secretory defect 2
- Often asymptomatic in early stages and can remain undiagnosed for many years 1, 2
- Frequently associated with obesity and physical inactivity 1, 2
- May initially be managed with lifestyle modifications and oral medications, but may eventually require insulin 1, 2
Important Clinical Considerations
The degree of hyperglycemia reflects the severity of the underlying metabolic process and its treatment more than the nature of the process itself. 1 The severity of metabolic abnormality can progress, regress, or stay the same over time. 1
Common Pitfall
It is less important to label the particular type of diabetes than to understand the pathogenesis of the hyperglycemia and treat it effectively. 1 Many diabetic individuals do not easily fit into a single class, and assigning a type often depends on circumstances present at diagnosis. 1