What are the primary classifications of diabetes mellitus and their key features?

Types of Diabetes Mellitus

Diabetes mellitus is classified into four primary categories: Type 1 diabetes (autoimmune β-cell destruction leading to absolute insulin deficiency), Type 2 diabetes (progressive β-cell dysfunction with insulin resistance), gestational diabetes mellitus (hyperglycemia first recognized in pregnancy), and specific types due to other causes (monogenic syndromes, pancreatic disease, drug-induced). 1

Type 1 Diabetes

Pathophysiology and Epidemiology:

• Results from autoimmune destruction of pancreatic β-cells, causing absolute insulin deficiency and accounts for 5-10% of all diabetes cases 1, 2, 3
• Autoantibodies (GAD-65, IA-2, ZnT8, anti-insulin) are present in 85-90% of individuals at diagnosis 2

Clinical Presentation:

• Children: Classic triad of polyuria, polydipsia, and weight loss; approximately 33-50% present with diabetic ketoacidosis (DKA) at diagnosis 1, 2
• Adults: More variable presentation without classic symptoms; may experience slower progression with transient remission of insulin requirement (latent autoimmune diabetes in adults, LADA) 1, 2

Diagnostic Pitfalls:

• Approximately 40% of adults newly diagnosed with Type 1 diabetes are initially misclassified as Type 2 2
• When suspecting Type 1 in adults, test for islet autoantibodies (GAD-65 first, then IA-2 and/or ZnT8 if negative) 2
• C-peptide measurement helps differentiate: <200 pmol/L suggests Type 1**, while **>200 pmol/L indicates residual β-cell function 2

Type 2 Diabetes

Pathophysiology and Epidemiology:

• Characterized by progressive, non-autoimmune loss of β-cell insulin secretion combined with insulin resistance 1
• Comprises 90-95% of all diabetes cases 1, 2, 3

Demographic Risk Factors:

• Ethnic disparities: Native Americans/Alaska Natives (15.1%), non-Hispanic African Americans (12.7%), Hispanics (12.1%), Asians (8.0%), non-Hispanic whites (7.4%) 3
• Age-related prevalence: 4% in ages 18-44 years, 17% in ages 45-64 years, 25% in those ≥65 years 3

Clinical Presentation:

• Often asymptomatic for years before diagnosis 1
• DKA can occur in Type 2 diabetes, particularly among ethnic and racial minority groups—a critical diagnostic pitfall 1

Gestational Diabetes Mellitus (GDM)

• Defined as diabetes first recognized in the second or third trimester of pregnancy that was not overt diabetes prior to conception 1, 3
• Prevalence varies widely based on population risk factors 3

Specific Types Due to Other Causes

Prevalence and Categories:

• Account for approximately 3-5% of all diagnosed diabetes 2, 3

Monogenic Diabetes Syndromes:

• Include neonatal diabetes and maturity-onset diabetes of the young (MODY) 1, 2
• Consider MODY when: mild stable fasting hyperglycemia, A1C 5.6-7.6%, multiple family members affected, absence of obesity 2
• All children diagnosed with diabetes in the first 6 months of life should have genetic testing 2

Exocrine Pancreatic Disease:

• Includes cystic fibrosis-related diabetes and pancreatitis-associated diabetes 1, 2

Drug- or Chemical-Induced:

• Associated with glucocorticoid therapy, antiretroviral regimens for HIV/AIDS, and post-transplant immunosuppression 1, 2
• Immune checkpoint inhibitors can precipitate acute autoimmune Type 1 diabetes 2

Critical Classification Considerations

Age-Related Paradigm Shift:

• The historic view that Type 1 occurs only in children and Type 2 only in adults is no longer accurate—both types occur across all age groups 1, 2

Diagnostic Evolution:

• Many patients cannot be clearly classified at initial diagnosis; the correct diagnosis becomes more evident over time as β-cell deficiency progresses 1
• Classification is critical for determining appropriate therapy and predicting disease course 1

AABBCC Clinical Tool for Type Differentiation

When distinguishing between Type 1 and Type 2 diabetes, systematically evaluate:

• Age: <35 years favors Type 1 2
• Autoimmunity: Personal or family history of autoimmune disease or polyglandular autoimmune syndrome 2
• Body habitus: BMI <25 kg/m² suggests Type 1 2
• Background: Family history of Type 1 diabetes 2
• Control: Inability to achieve glycemic targets with non-insulin agents suggests Type 1 2
• Comorbidities: Recent immune checkpoint inhibitor use 2

Laboratory confirmation: Standardized islet autoantibody testing is recommended for adults with phenotypic overlap (younger age, weight loss, ketoacidosis, rapid insulin requirement) 2