What type of diabetes is characterized by onset at age 25, initial response to Oral Hypoglycemic Agents (OHAs), normal fasting C-peptide levels, and requirement for insulin therapy after 3 years?

Latent Autoimmune Diabetes in Adults (LADA)

This clinical presentation is most consistent with Latent Autoimmune Diabetes in Adults (LADA), a slowly progressive form of autoimmune type 1 diabetes that initially responds to oral agents but progresses to insulin dependence within a few years. 1, 2

Key Diagnostic Features Present

The constellation of findings strongly supports LADA:

• Age 25 at onset falls within the typical LADA range (adult-onset, typically diagnosed before age 35) 1, 3
• Initial response to oral hypoglycemic agents for several months is characteristic, distinguishing LADA from classic type 1 diabetes which requires immediate insulin 2, 4
• Normal fasting C-peptide levels indicate preserved beta-cell function at diagnosis, consistent with the slower autoimmune destruction seen in LADA 1, 5
• Progression to insulin requirement within 3 years matches the natural history of LADA, where most patients require insulin within 2-3 years as autoimmune destruction continues 2, 6

Critical Next Step: Autoantibody Testing

You must check islet autoantibodies immediately to confirm the diagnosis. 1, 7

• GAD65 (glutamic acid decarboxylase) antibody should be tested first as it is the most frequently positive autoantibody in LADA (present in >80% of cases) 2, 7
• If GAD65 is negative, follow with IA-2 (tyrosine phosphatase) and ZnT8 (zinc transporter 8) antibodies 3, 1
• Positive autoantibodies confirm autoimmune diabetes and distinguish LADA from type 2 diabetes 3

Why This Is Not Type 2 Diabetes

Several features argue strongly against type 2 diabetes:

• Rapid progression to insulin dependence within 3 years is atypical for type 2 diabetes in a 25-year-old 2, 6
• Normal C-peptide with progression to insulin need suggests ongoing autoimmune destruction rather than insulin resistance 5, 7
• Young age at onset (25 years) with insulin requirement makes type 2 diabetes less likely unless there is significant obesity (not mentioned here) 1, 3

Why This Is Not Classic Type 1 Diabetes

The presentation differs from typical type 1 diabetes:

• Initial response to oral agents for several months indicates slower beta-cell destruction than classic type 1 diabetes, which typically requires immediate insulin 3
• Normal C-peptide at diagnosis shows preserved insulin secretion, whereas classic type 1 diabetes often presents with very low or undetectable C-peptide 3, 5
• Absence of ketoacidosis at presentation (implied by successful OHA treatment) is more consistent with LADA's gradual onset 4, 6

Consider MODY as Alternative Diagnosis

While LADA is most likely, Maturity-Onset Diabetes of the Young (MODY) should be considered if autoantibodies are negative:

• Age <25 years at diagnosis is characteristic of MODY 1, 3
• Normal C-peptide indicates preserved beta-cell function seen in MODY 1, 5
• However, progression to insulin within 3 years argues against most MODY subtypes, which typically maintain oral agent responsiveness for longer periods 1, 3
• If autoantibodies are negative, check for family history of diabetes in one parent (autosomal dominant pattern) and consider genetic testing for HNF1A, GCK, HNF4A, and HNF1B mutations 1

Critical Pitfall to Avoid

Do not rely solely on "normal" C-peptide to rule out autoimmune diabetes. 7, 5

• A C-peptide of 1.3 ng/mL (approximately 430 pmol/L) is technically normal but represents the low-normal range 7
• In the context of hyperglycemia requiring insulin, this C-peptide level indicates relative insulin deficiency and should prompt autoantibody testing 7, 5
• Approximately 5-10% of adults with autoimmune diabetes are initially antibody-negative, so if clinical suspicion remains high despite negative antibodies, repeat testing in 6-12 months 3, 8

Management Implications

Once LADA is confirmed:

• Insulin therapy is the appropriate treatment, as oral agents will progressively fail due to ongoing beta-cell destruction 2, 4
• Basal-bolus insulin regimen should be initiated and titrated to achieve glycemic control 7
• Screen for other autoimmune conditions including thyroid disease (Hashimoto's, Graves'), celiac disease, Addison's disease, and pernicious anemia 3
• Monitor C-peptide annually to track beta-cell function decline 2, 6