What is Diabetes Mellitus?
Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both, which leads to long-term damage and dysfunction of multiple organs including the eyes, kidneys, nerves, heart, and blood vessels. 1
Core Pathophysiology
The fundamental problem in diabetes involves deficient insulin action on target tissues, which stems from either inadequate insulin secretion, diminished tissue responses to insulin, or both mechanisms occurring simultaneously. 1 The pathogenic processes range across a spectrum:
- Autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency (Type 1 diabetes) 1
- Insulin resistance with progressive β-cell dysfunction (Type 2 diabetes) 2
- Combined defects where impaired insulin secretion and insulin resistance frequently coexist in the same patient, making it unclear which abnormality primarily drives the hyperglycemia 1
This deficient insulin action disrupts carbohydrate, fat, and protein metabolism throughout the body. 1
Clinical Manifestations
Acute Symptoms
When hyperglycemia becomes marked, patients develop classic symptoms:
- Polyuria (excessive urination) 1
- Polydipsia (excessive thirst) 1
- Weight loss, sometimes accompanied by polyphagia (excessive hunger) 1
- Blurred vision 1
- Impaired growth and increased susceptibility to infections in chronic cases 1
Life-Threatening Acute Complications
Uncontrolled diabetes can rapidly progress to:
These conditions can develop within hours if left untreated and represent medical emergencies. 3
Long-Term Complications Affecting Morbidity and Mortality
The chronic hyperglycemia triggers damaging biochemical pathways involving oxidative stress, inflammation, and microvascular dysfunction. 4
Microvascular Complications
- Retinopathy with potential vision loss 1
- Nephropathy progressing to renal failure 1
- Peripheral neuropathy creating risk for foot ulcers, amputations, and Charcot joints 1
- Autonomic neuropathy causing gastrointestinal, genitourinary, cardiovascular symptoms, and sexual dysfunction 1
Macrovascular Complications
- Atherosclerotic cardiovascular disease 1
- Peripheral arterial disease 1
- Cerebrovascular disease 1
- Hypertension and lipoprotein metabolism abnormalities frequently accompany diabetes 1
Major Types of Diabetes
Type 1 Diabetes
Accounts for only 5-10% of diabetes cases and results from cellular-mediated autoimmune destruction of pancreatic β-cells. 1 This leads to absolute insulinopenia requiring exogenous insulin for survival. 3 Patients are characterized by the presence of islet cell autoantibodies in 85-90% of cases at diagnosis. 4
Type 2 Diabetes
The most common form, characterized by insulin resistance and progressive insulin secretory defects. 2 Often asymptomatic in early stages and discovered during screening. 2 Frequently associated with obesity and physical inactivity, and may initially respond to lifestyle modifications and oral medications but can eventually require insulin therapy. 2
Other Categories
- Gestational diabetes mellitus 1
- Specific types due to other causes (pancreatic disease, drug-induced, genetic defects) 4
Critical Clinical Pitfall
Classification of diabetes type at presentation is less important than understanding the pathogenesis of hyperglycemia and treating it effectively. 1 Many patients don't fit neatly into a single category, and their classification may change over time based on disease progression or resolution of precipitating factors. 1