What is the difference between type 1 (T1DM) and type 2 (T2DM) diabetes mellitus?

Differences Between Type 1 and Type 2 Diabetes Mellitus

Type 1 diabetes results from autoimmune destruction of pancreatic β-cells causing absolute insulin deficiency, while type 2 diabetes stems from progressive β-cell dysfunction combined with insulin resistance. 1, 2

Pathophysiological Distinctions

Type 1 Diabetes

• Autoimmune β-cell destruction renders the pancreas unable to synthesize and secrete insulin, leading to complete or near-complete insulin deficiency 1, 3
• Islet autoantibodies (to insulin, glutamic acid decarboxylase, islet antigen 2, or zinc transporter 8) are present and predictive of disease progression 2
• The disease progresses through three distinct stages: Stage 1 (two or more autoantibodies with normoglycemia), Stage 2 (autoantibodies with dysglycemia), and Stage 3 (clinical diabetes with symptomatic hyperglycemia) 1, 3, 2
• Accounts for approximately 5-10% of all diabetes cases 2
• Ketosis susceptibility is characteristic due to absolute insulin deficiency, with approximately one-third of children presenting with diabetic ketoacidosis at diagnosis 1, 3, 2

Type 2 Diabetes

• Progressive loss of β-cell insulin secretion occurs on the background of insulin resistance, not autoimmune destruction 1, 2
• Pathways to β-cell dysfunction include genetic predisposition, epigenetic changes, inflammation, and metabolic stress 2
• Represents 85-95% of diabetes cases in developed countries 1
• Obesity is present in approximately 80% of youth with type 2 diabetes, serving as a pathogenetic factor through insulin resistance 1

Clinical Presentation Differences

Type 1 Diabetes

• Classic triad: polyuria, polydipsia, and unintentional weight loss from osmotic diuresis and inability to utilize glucose 1, 3, 2
• Approximately one-third present with diabetic ketoacidosis, particularly in children 1, 3, 2
• Traditionally associated with childhood onset, though adults can develop type 1 diabetes with more variable presentation 1, 2

Type 2 Diabetes

• Gradual onset with symptoms that may be subtle or absent, often discovered during routine screening 2
• Significant comorbidities at diagnosis including hypertension, dyslipidemia, and microalbuminuria 1
• Increasingly diagnosed in children and adolescents, particularly ethnic minorities with obesity 1, 2
• Occasionally presents with diabetic ketoacidosis, particularly in ethnic minorities, which can complicate initial diagnosis 1

Diagnostic Approach

The AABBCC framework helps distinguish diabetes types: Age at onset, Autoantibodies (presence suggests type 1), Body habitus (obesity suggests type 2), Background (family history and ethnicity), Control (rapid vs. gradual progression), and Comorbidities (metabolic syndrome features suggest type 2) 2

Key Diagnostic Pitfalls

• Up to 40% of adults with new type 1 diabetes are initially misdiagnosed as having type 2 diabetes 2
• Distinction can be difficult in children since autoantibodies and ketosis may be present in patients with features of type 2 diabetes (obesity, acanthosis nigricans) 1
• Some patients cannot be clearly classified at diagnosis, and the true diagnosis becomes more obvious over time 1

Management Differences

Type 1 Diabetes

• Lifelong insulin therapy is mandatory from diagnosis due to absolute insulin deficiency 3, 4
• Carbohydrate counting and insulin dose adjustment are essential skills 2
• Continuous glucose monitoring is increasingly important for optimal glycemic control 2
• Subcutaneous insulin creates an imbalance between hepatic and peripheral insulin effects because it bypasses first-pass hepatic metabolism 3

Type 2 Diabetes

• Initial therapy begins with lifestyle modifications and metformin, not insulin 2
• Weight management is a cornerstone of therapy given the pathogenic role of obesity 1, 2
• Treatment may progress to include various oral medications, GLP-1 receptor agonists, SGLT2 inhibitors, and eventually insulin as β-cell function declines 2
• Screening for comorbidities (hypertension, dyslipidemia, microalbuminuria) and complications should begin at diagnosis 1

Complications

Both types lead to identical chronic complications (retinopathy, nephropathy, neuropathy, cardiovascular disease), though rates of progression may differ 1, 2

Important Clinical Caveats

• The traditional paradigm that type 1 occurs only in children and type 2 only in adults is no longer accurate—both diseases occur in both age groups 1, 2
• Genetic testing may be warranted when clinical features suggest monogenic forms of diabetes (MODY) 2
• Insulin resistance is increasingly recognized in type 1 diabetes, particularly with obesity (40% of adolescents with type 1 diabetes are overweight or obese), creating a "double diabetes" phenotype that worsens cardiovascular risk 1