What are the differences in pathophysiology and management between type 1 diabetes and type 2 diabetes in an adult patient?

Type 1 vs Type 2 Diabetes: Key Differences

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 occurring on a background of insulin resistance. 1

Pathophysiological Distinctions

Type 1 Diabetes

• Autoimmune destruction of pancreatic β-cells leads to absolute insulin deficiency requiring lifelong exogenous insulin 2
• Presence of two or more islet autoantibodies (to insulin, glutamic acid decarboxylase, islet antigen 2, or zinc transporter 8) is an almost certain predictor of clinical diabetes 2, 1
• Progresses through three distinct stages: Stage 1 (autoimmunity with normoglycemia), Stage 2 (autoimmunity with dysglycemia), and Stage 3 (overt hyperglycemia with symptoms) 2
• Accounts for approximately 5-10% of all diabetes cases 1
• In insulin deficiency states, glucose uptake by cells is severely impaired, and mitochondrial dysfunction leads to ketone body generation 2

Type 2 Diabetes

• Progressive loss of β-cell insulin secretion combined with insulin resistance is the fundamental defect 2
• Pathways to β-cell dysfunction include genetic predisposition, epigenetic changes, inflammation, and metabolic stress 1
• The metabolic disorder can develop even in the normoglycemic state (termed "euglycemic dysmetabolism"), distinguishing it fundamentally from type 1 diabetes 2
• Characterized by hyperinsulinemia and altered signal transduction systems rather than absolute insulin deficiency 2

Clinical Presentation Differences

Type 1 Diabetes Presentation

• Classic triad: polyuria, polydipsia, and unintentional weight loss 1
• Approximately one-third of children present with diabetic ketoacidosis (DKA) 2, 1
• Onset may be more variable in adults and may not present with hallmark symptoms 2
• Traditionally associated with childhood onset but can occur at any age 1

Type 2 Diabetes Presentation

• Gradual onset of symptoms, often asymptomatic and discovered during routine screening 1
• Increasingly seen in children and adolescents, particularly those with obesity 1
• May occasionally present with DKA, particularly in ethnic minorities (up to 3.2 per 1,000 person-years) 3
• Historically, 5-25% of children with type 2 diabetes present with ketoacidosis 3

Diagnostic Approach

Laboratory Criteria

• Both types diagnosed using fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during OGTT, or A1C ≥6.5% 2
• A1C testing must be NGSP-certified and DCCT-standardized to avoid misdiagnosis 2
• In conditions with altered A1C-glycemia relationship (sickle cell disease, pregnancy, G6PD deficiency, HIV, hemodialysis), use only plasma glucose criteria 2

Distinguishing Between Types

• Use the AABBCC approach: Age, Autoimmunity (islet antibodies), Body habitus, Background (family history), Control (C-peptide levels), and Comorbidities 1
• Misdiagnosis is common: up to 40% of adults with new type 1 diabetes are initially misdiagnosed as having type 2 1
• Classification may not be straightforward at presentation, but diagnosis becomes more obvious over time 2

Management Differences

Type 1 Diabetes Management

• Absolute requirement for exogenous insulin from diagnosis 1
• Implement basal-bolus insulin regimen using rapid-acting analogs (e.g., insulin aspart) before meals and long-acting basal insulin 4, 5
• Carbohydrate counting and insulin dose adjustment are essential skills 1
• Continuous glucose monitoring is increasingly important for optimal control 1
• Never discontinue basal insulin even during illness or fasting to prevent DKA 3

Type 2 Diabetes Management

• Initial therapy: lifestyle modifications and metformin 1
• Progressive approach: add oral medications, GLP-1 receptor agonists, SGLT2 inhibitors as needed 1
• Weight management is a cornerstone of therapy 1
• Eventually may require insulin as β-cell function declines 1
• SGLT2 inhibitors carry DKA risk (0.6-4.9 events per 1,000 patient-years; relative risk 2.46) and can cause euglycemic DKA 3

Critical Clinical Pitfalls

DKA in Type 2 Diabetes

• Do not assume DKA cannot occur in type 2 diabetes based on diagnosis alone 3
• Precipitating factors include severe physiologic stress, SGLT2 inhibitors, glucocorticoids, second-generation antipsychotics, cocaine use, and insulin omission 3
• Euglycemic DKA (glucose <200 mg/dL) occurs in approximately 10% of DKA cases, particularly with SGLT2 inhibitor use 3
• Type 2 diabetes patients with DKA require longer treatment times (36.0 vs 28.9 hours) to achieve ketone-free urine 3

Overlapping Features

• Both types can develop identical chronic complications (retinopathy, nephropathy, neuropathy, cardiovascular disease), though progression rates may differ 2, 1
• Traditional paradigms of age-based classification are no longer accurate—both diseases occur in all age groups 2
• Some patients present with mixed features of both DKA and hyperosmolar hyperglycemic state 3