What type of diabetes is a 20-year-old female with a body mass index (BMI) of 26 kg/m², elevated hemoglobin A1c (HbA1c), normal C-peptide level, and negative autoimmune test results most likely to have, type 2 diabetes or maturity-onset diabetes of the young (MODY)?

Diagnostic Classification: MODY vs Type 2 Diabetes

This 20-year-old female most likely has maturity-onset diabetes of the young (MODY) rather than type 2 diabetes, based on her young age, modest HbA1c elevation (7.4%), normal C-peptide level, negative autoimmune markers, and only mildly elevated BMI. 1

Algorithmic Approach to Classification

Step 1: Rule Out Type 1 Diabetes

• Autoimmune markers are negative – This excludes immune-mediated type 1 diabetes 1
• Normal C-peptide level – This indicates preserved pancreatic beta-cell function, inconsistent with type 1 diabetes which typically shows C-peptide <200 pmol/L 1, 2
• At age 20 with negative antibodies, 5-10% of adult-onset type 1 diabetes cases are antibody-negative, but the normal C-peptide makes this unlikely 1

Step 2: Evaluate for MODY Features

This patient has multiple features strongly suggesting MODY: 1

• Age <35 years at diagnosis – MODY typically presents before age 25 years 1
• HbA1c 7.4% (<7.5% or <58 mmol/mol) – Modest hyperglycemia at diagnosis is characteristic of MODY 1
• Normal C-peptide – Indicates preserved insulin secretion with minimal insulin resistance, typical of MODY 1, 2
• BMI 26 kg/m² – Only mildly elevated, not the marked obesity typically seen in type 2 diabetes 1, 3

Step 3: Assess Against Type 2 Diabetes Criteria

Features arguing AGAINST type 2 diabetes: 1

• Young age (20 years) – Type 2 diabetes typically occurs in older adults, though increasingly seen in younger populations 1
• BMI 26 kg/m² – While technically overweight, this is much lower than the typical BMI ≥30 kg/m² seen in young-onset type 2 diabetes 1, 3
• Normal C-peptide without insulin resistance – Type 2 diabetes is characterized by insulin resistance with elevated or inappropriately normal C-peptide for the degree of hyperglycemia 1
• Modest HbA1c elevation – The relatively mild hyperglycemia (7.4%) at presentation is more consistent with MODY than type 2 diabetes 1

Critical Distinguishing Features

C-Peptide Interpretation

• Normal C-peptide with hyperglycemia indicates preserved beta-cell function without the severe insulin resistance of type 2 diabetes 2, 3
• In type 2 diabetes at this age and BMI, you would expect either elevated C-peptide (indicating insulin resistance) or low C-peptide (indicating beta-cell failure after prolonged disease) 3, 4
• C-peptide values >600 pmol/L suggest type 2 diabetes, while values 200-600 pmol/L are consistent with MODY 1, 2

BMI as a Discriminator

• BMI is a crucial differentiating factor between MODY and familial type 2 diabetes 3
• MODY patients typically have normal or only mildly elevated BMI, whereas young-onset type 2 diabetes patients are usually significantly overweight or obese 1, 3
• At BMI 26 kg/m², this patient falls into the MODY phenotype rather than the typical type 2 diabetes phenotype 3

Next Steps for Confirmation

Recommended Testing

1. Obtain detailed family history – Look specifically for one parent with diabetes and autosomal dominant inheritance pattern (diabetes in multiple generations) 1
2. Check for specific MODY features – Screen for renal cysts, partial lipodystrophy, maternally inherited deafness, or severe insulin resistance without obesity 1
3. Calculate MODY probability – Use the monogenic diabetes prediction model at diabetesgenes.org/exeter-diabetes-app/ModyCalculator (probability >5% warrants genetic testing) 1
4. Genetic testing – If clinical features support MODY, test for common mutations (HNF1A, GCK, HNF4A, HNF1B) 1, 3

Important Clinical Caveats

Pitfalls to Avoid

• Do not assume type 2 diabetes based solely on BMI ≥25 kg/m² – This cutoff is used to identify features of type 2 diabetes, but in a 20-year-old with other MODY features, it should not override the diagnosis 1
• Young age does not automatically mean type 1 diabetes – With negative antibodies and normal C-peptide, consider MODY before defaulting to type 1 diabetes 1
• MODY can coexist with type 1 diabetes – Rarely, patients with MODY can develop autoimmune type 1 diabetes later, so monitor for metabolic deterioration 5

Treatment Implications

• MODY patients often respond to oral agents (particularly sulfonylureas for HNF1A/HNF4A mutations) rather than requiring insulin 3
• Genetic diagnosis changes management – Confirming MODY allows for targeted therapy and family screening 1, 3
• If genetic testing is negative or unavailable, treat based on clinical phenotype and monitor response to therapy 1

Monitoring Strategy

• Follow glycemic control closely – If control worsens unexpectedly despite appropriate therapy, recheck autoimmune markers as type 1 diabetes can develop later 5
• Screen family members – If MODY is confirmed genetically, cascade screening of first-degree relatives is indicated 1, 3