Can type 1 diabetes mellitus develop in adults, particularly those presenting with new‑onset hyperglycemia, low body mass index, rapid insulin requirement, or a family history of autoimmune disease?

Can Type 1 Diabetes Occur in Adulthood?

Yes, type 1 diabetes absolutely occurs in adulthood and is far more common than traditionally recognized—immune-mediated diabetes can develop at any age, even into the 8th and 9th decades of life. 1

Epidemiology and Prevalence

The outdated paradigm that type 1 diabetes is exclusively a childhood disease is fundamentally incorrect. Recent epidemiological data demonstrate that nearly half of all type 1 diabetes cases are diagnosed in adulthood, with adult-onset type 1 diabetes accounting for a substantial proportion of cases worldwide. 2, 3 The American Diabetes Association explicitly states that immune-mediated diabetes "commonly occurs in childhood and adolescence, but it can occur at any age, even in the 8th and 9th decades of life." 1

Clinical Presentation in Adults

Key Distinguishing Features

Adults presenting with type 1 diabetes exhibit several characteristic patterns that differ from typical type 2 diabetes:

• Slower β-cell destruction: Adults may retain sufficient β-cell function to prevent diabetic ketoacidosis (DKA) for many years, with a more gradual progression to insulin dependence compared to children. 1

• Variable insulin requirements: Some adults may experience remission with decreased insulin needs for months or years before eventually becoming insulin-dependent. 1

• Preserved C-peptide: Adults with long-duration type 1 diabetes show greater persistence of C-peptide compared to children, reflecting slower β-cell loss. 2

Latent Autoimmune Diabetes in Adults (LADA)

LADA represents a slower-progressing form of autoimmune diabetes in adults, accounting for approximately 5-10% of adults initially diagnosed with apparent type 2 diabetes. 4, 5 This subtype is characterized by:

• Presence of islet autoantibodies (particularly GAD antibodies) distinguishing it from type 2 diabetes 4, 5
• Progression to insulin dependence typically over years rather than weeks to months 4
• Lower BMI and fewer metabolic risk factors compared to true type 2 diabetes 4

Diagnostic Challenges and Misclassification

Critical Pitfall: Misdiagnosis as Type 2 Diabetes

Approximately 40% of adults who develop type 1 diabetes are initially misdiagnosed as having type 2 diabetes, leading to delays in appropriate insulin therapy. 4 This misclassification occurs because:

• Type 2 diabetes is highly prevalent in adults, creating diagnostic bias 2
• Obesity and metabolic syndrome are increasingly common in adults with type 1 diabetes (24% overweight, 15% obese in U.S. registry data), blurring clinical distinctions 1, 2
• Adults may not present with classic DKA at onset 1

When to Suspect Adult-Onset Type 1 Diabetes

Test for islet autoantibodies in adults presenting with diabetes who have ANY of these clinical features: 4, 5

• Age <35 years at diagnosis
• Unintentional weight loss or lean body habitus (low BMI)
• Ketoacidosis or ketosis at presentation
• Rapid progression to insulin requirement
• Acute symptom onset
• Personal or family history of autoimmune disease (thyroid disease, celiac disease, vitiligo, Addison disease) 1, 4

Diagnostic Workup

Autoantibody Testing Algorithm

Start with GAD antibody testing, as this is the most frequently positive marker in adult-onset type 1 diabetes (present in 70-80% of cases). 5 If GAD antibodies are negative but clinical suspicion remains high, test for IA-2 and ZnT8 antibodies to increase diagnostic sensitivity. 5

The presence of two or more islet autoantibodies indicates 70% risk of progression to insulin dependence within 10 years (44% at 5 years), providing strong diagnostic certainty. 5 However, a single positive autoantibody carries only 15% risk and may represent a false-positive. 5

Important Testing Limitations

• 5-10% of true autoimmune diabetes cases are antibody-negative, so treatment decisions should be based on clinical phenotype and monitoring for progression, not antibody results alone. 4, 5
• Autoantibody prevalence varies by race: 85-90% in white patients versus only 19% in Black or Hispanic patients with type 1 diabetes. 4
• Autoantibodies decrease with age and duration of disease. 4

C-Peptide Assessment

C-peptide testing helps assess residual β-cell function:

• Values <200 pmol/L (<0.6 ng/mL) indicate significant β-cell loss 5
• Values >600 pmol/L (>1.8 ng/mL) suggest preserved β-cell function 5

Genetic and Immunologic Differences

Adults with type 1 diabetes show distinct patterns compared to children:

• Different genetic risk profiles and total genetic burden 2
• Variations in the type and number of autoantibodies present 2
• Slower rates of C-peptide decline 2
• Children diagnosed before age 7 often have more aggressive disease, more autoantibodies, and stronger genetic risk factors 6

Associated Autoimmune Conditions

Screen all adults diagnosed with type 1 diabetes for additional autoimmune disorders, including thyroid disease, celiac disease, adrenal insufficiency, and pernicious anemia. 1, 4 Personal or family history of these conditions increases the likelihood of autoimmune diabetes. 4

Emerging Triggers

Recent evidence identifies new triggers for adult-onset type 1 diabetes:

• Checkpoint inhibitor therapy can cause autoimmune diabetes in adults with high-risk HLA haplotypes, unpredictable by family history or baseline autoantibodies. 1
• SARS-CoV-2 infection has been associated with increased cases of new-onset diabetes, hyperglycemia, and DKA during the COVID-19 pandemic. 1

Quality Standards for Testing

Autoantibody testing must be performed only in accredited laboratories with established quality control programs and participation in proficiency testing programs to ensure diagnostic accuracy. 5