What are the different types of diabetes mellitus?

Classification of Diabetes Mellitus

Diabetes mellitus is classified into four main categories: Type 1 diabetes (5-10% of cases), Type 2 diabetes (90-95% of cases), gestational diabetes mellitus, and specific types due to other causes (3-5% of cases). 1, 2, 3

Type 1 Diabetes

Pathophysiology and Epidemiology:

• Results from autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency 1, 2, 3
• Accounts for approximately 5-10% of all diabetes cases 2, 3
• Islet autoantibodies (GAD-65, IA-2, ZnT8, insulin antibodies) are present in 85-90% of individuals at diagnosis 2, 4

Clinical Presentation:

• In children: classic symptoms include polyuria and polydipsia, with 33-50% presenting with diabetic ketoacidosis (DKA) at diagnosis 2, 4
• In adults: presentation is more variable and may not include classic childhood symptoms; can progress more slowly toward insulin requirement (latent autoimmune diabetes in adults, LADA) 1, 2, 4

Diagnostic Pitfall:

• Approximately 40% of adults newly diagnosed with Type 1 diabetes are initially misclassified as having Type 2 diabetes 2
• When Type 1 diabetes is suspected in adults, test for islet autoantibodies first (GAD as primary, followed by IA-2 and/or ZnT8 if negative) 2, 4

Type 2 Diabetes

Pathophysiology and Epidemiology:

• Characterized by progressive, non-autoimmune loss of β-cell insulin secretion combined with insulin resistance 1, 2, 3
• Represents 90-95% of all diabetes cases 2, 3
• Prevalence varies significantly by ethnicity: Native Americans/Alaska Natives (15.1%), non-Hispanic African Americans (12.7%), Hispanics (12.1%), Asians (8.0%), and non-Hispanic whites (7.4%) 2, 3
• Prevalence increases with age: 4% in ages 18-44,17% in ages 45-64, and 25% in those ≥65 years 2, 3

Clinical Presentation:

• Although uncommon, DKA can occur in Type 2 patients, especially among certain ethnic and racial minority groups 2

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, 2, 3
• Screening recommended for all pregnant women at 24-28 weeks gestation using either a one-step 75-g OGTT or two-step approach (50-g non-fasting screen followed by 100-g OGTT if positive) 4
• Women with GDM should be screened for persistent diabetes at 4-12 weeks postpartum using 75-g OGTT and require lifelong screening at least every 3 years 4

Specific Types Due to Other Causes

Prevalence and Categories:

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

Monogenic Diabetes Syndromes:

• Include neonatal diabetes and maturity-onset diabetes of the young (MODY) 1, 2
• Consider MODY in patients with: mild stable fasting hyperglycemia, stable A1C between 5.6-7.6%, multiple family members with non-typical Type 1 or Type 2 diabetes, and absence of obesity 2, 4
• All children diagnosed with diabetes in the first 6 months of life should have genetic testing 2, 4

Exocrine Pancreatic Disease:

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

Drug or Chemical-Induced Diabetes:

• Associated with glucocorticoid therapy, certain antiretroviral regimens (HIV/AIDS treatment), and post-transplant immunosuppression 1, 2, 4

AABBCC Clinical Tool for Differentiating Diabetes Types

This evidence-based framework helps distinguish Type 1 from Type 2 diabetes 2:

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

Critical Classification Considerations

Age-Related Paradigm Shift:

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

Diagnostic Evolution:

• Assigning a diabetes type often depends on circumstances at diagnosis, with individuals not necessarily fitting clearly into a single category 1
• Over time, the degree of β-cell deficiency becomes clearer, making correct classification more evident 1, 2

Laboratory Confirmation:

• Standardized islet autoantibody testing (GAD-65 primary, followed by IA-2 and/or ZnT8 if negative) is recommended for adults with phenotypic overlap (younger age at onset, weight loss, ketoacidosis, rapid need for insulin) 2
• C-peptide measurement serves as a stable surrogate marker: >200 pmol/L suggests residual β-cell function, while <200 pmol/L suggests Type 1 diabetes 2