Why is the diagnosis of type I (insulin-dependent) diabetes increasing in adults?

Why More Adults Are Being Diagnosed with Type 1 Diabetes

The apparent increase in adult-onset type 1 diabetes diagnoses reflects both a true rise in incidence and prevalence of the disease across all ages, and improved recognition of a condition that has historically been misclassified as type 2 diabetes in adults. 1, 2

True Epidemiological Increase

The incidence and prevalence of type 1 diabetes are genuinely increasing across all age groups, not just in children. 1

• More than half of all new type 1 diabetes cases now occur in adults, representing a substantial shift from historical patterns where this was considered primarily a childhood disease. 2, 3
• Type 1 diabetes can occur at any age, even in the 8th and 9th decades of life, though this has been underappreciated historically. 1
• The rate of β-cell destruction varies considerably, being rapid in children but often slower in adults, which means adults may retain sufficient β-cell function to avoid diabetic ketoacidosis (DKA) for years after disease onset. 1

Historical Misclassification and Improved Recognition

A major factor in the apparent increase is better recognition of adult-onset type 1 diabetes that was previously misdiagnosed as type 2 diabetes. 2, 3, 4

• At least one in three adults with type 1 diabetes are initially misclassified as having type 2 diabetes, leading to inappropriate treatment with oral agents rather than insulin. 3
• Adults with type 1 diabetes may not require insulin at diagnosis, their clinical presentation can masquerade as type 2 diabetes, and the rising prevalence of obesity in the general population further blurs the clinical distinction. 2, 3
• The dominance of type 2 diabetes in adults (90-95% of all diabetes cases) creates a low prior probability setting where clinicians default to assuming type 2 diabetes without considering autoimmune etiology. 5, 4

Key Differences in Adult-Onset Type 1 Diabetes

Adults presenting with type 1 diabetes exhibit distinct characteristics compared to children, which contributes to diagnostic confusion:

• Lower HLA-associated genetic risk with more protective genotypes and lower genetic risk scores compared to childhood-onset cases. 2, 3
• Fewer and different autoantibodies, though glutamic acid decarboxylase antibodies (GADA) remain dominant; multiple autoantibodies are less common than in children. 6, 2
• Slower progression to insulin dependence (typically over years rather than weeks to months), with higher C-peptide levels at diagnosis and less frequent presentation with DKA (25-50% vs. higher rates in children). 1, 6, 2
• Increasing prevalence of obesity and metabolic syndrome in adults with type 1 diabetes, which was historically uncommon but is now increasingly recognized and should not preclude the diagnosis. 1, 3

Emerging Iatrogenic Causes

A novel contributor to adult-onset type 1 diabetes is immune checkpoint inhibitor therapy for cancer treatment. 1

• Type 1 diabetes occurs in just under 1% of patients treated with checkpoint inhibitors, most commonly with agents blocking the programmed cell death protein 1/programmed cell death ligand 1 pathway. 1
• The majority of these cases occur in people with high-risk HLA-DR4 (present in 76% of affected individuals), and risk cannot currently be predicted by family history or autoantibodies. 1
• All healthcare professionals administering these medications must be mindful of this adverse effect and monitor patients appropriately. 1

Clinical Implications

The key pitfall is assuming all adult-onset diabetes is type 2 diabetes without considering autoimmune etiology, particularly in patients who are lean, have unintentional weight loss, progress rapidly to insulin requirement, or present with DKA. 6, 2

• Current diagnostic tools including autoantibody testing (particularly GADA) and C-peptide measurement are underutilized in adults, leading to delayed appropriate treatment. 6, 3
• Islet autoantibody testing should be ordered when type 1 diabetes is clinically suspected based on features such as younger age (<35 years), lower BMI, unintentional weight loss, ketoacidosis, or rapid progression to insulin requirement. 6
• C-peptide levels help distinguish diabetes types: <200 pmol/L indicates severe β-cell deficiency consistent with type 1 diabetes, while >600 pmol/L suggests type 2 diabetes. 6, 7