What is the recommended screening method and frequency for type 1 diabetes mellitus (T1DM) in patients with cystic fibrosis (CF)?

Screening for Type 1 Diabetes in Cystic Fibrosis: OGTT Annually Starting at Age 10

The correct answer is D: OGTT annually, beginning at age 10 years in all patients with cystic fibrosis who have not been previously diagnosed with cystic fibrosis-related diabetes (CFRD). 1, 2

Recommended Screening Protocol

Annual oral glucose tolerance testing (OGTT) should begin by age 10 years in all patients with cystic fibrosis not previously diagnosed with CFRD. 1 This is a Level B recommendation from the American Diabetes Association Standards of Care, consistently maintained across multiple years (2015-2024). 1

Why OGTT is the Gold Standard

• OGTT is the only recommended screening test for CFRD, as it has superior sensitivity compared to other methods. 1, 2
• The test identifies both overt diabetes and intermediate glucose abnormalities that predict future CFRD development. 3, 4
• OGTT can detect abnormal glucose metabolism in approximately 59% of children with CF who would otherwise be missed. 5

Why Other Options Are Incorrect

A1C Every 6 Months (Option A) - NOT Recommended

A1C is explicitly NOT recommended as a screening test for CFRD due to low sensitivity. 1, 2 Key reasons include:

• A1C has poor sensitivity for detecting early glucose abnormalities in CF patients. 1, 2
• While an A1C ≥6.5% (≥48 mmol/mol) is consistent with a diagnosis of CFRD, it should not be used for screening. 1
• A1C cut-point thresholds of 5.5-5.8% might detect >90% of cases, but this approach is still under investigation and not yet recommended for routine screening. 1

Fasting Blood Glucose Annually (Option B) - Insufficient

Fasting glucose alone is inadequate for CFRD screening. 6 Evidence shows:

• Even using the lowered ADA cut-off for impaired fasting glucose (5.6 mmol/L), sensitivity is only 82% with specificity of 70% for identifying diabetic OGTTs. 6
• This approach is "definitely unsuitable" for early identification of CFRD and cannot replace annual OGTTs. 6
• Many CF patients have normal fasting glucose but abnormal post-challenge values. 3, 4

No Screening Until Age 18 (Option C) - Dangerous Delay

Delaying screening until age 18 misses critical early diagnosis opportunities. 1, 2 This is problematic because:

• CFRD occurs in approximately 20% of adolescents with CF. 1, 2
• Early diagnosis and treatment of CFRD is associated with preservation of lung function. 1
• Diabetes in CF patients is associated with worse nutritional status, more severe inflammatory lung disease, and greater mortality. 1, 2

Clinical Rationale for Early Screening

Pathophysiology of CFRD

• Insulin insufficiency is the primary defect in CFRD, related to partial fibrotic destruction of pancreatic islet mass. 1, 2
• Genetically determined β-cell function and insulin resistance from infection/inflammation also contribute. 1, 2
• The prevalence increases markedly with age, affecting 40-50% of adults with CF. 1

Impact on Outcomes

• Early diagnosis and treatment improves prognosis and preserves lung function. 1, 4
• CFRD is the most common comorbidity in CF patients. 1, 2
• The gap in mortality between CF patients with and without diabetes has narrowed with improved screening and aggressive insulin therapy. 1

Important Clinical Caveats

Earlier Screening Indications

Regardless of age, weight loss or failure of expected weight gain is a risk factor for CFRD and should prompt immediate screening. 1, 2 Do not wait until age 10 if these red flags are present.

Screening Before Age 10

• While screening before age 10 can identify risk for progression to CFRD, no benefit has been established with respect to weight, height, BMI, or lung function in asymptomatic children. 1
• Therefore, routine screening before age 10 is not recommended unless clinical concerns arise. 1

Follow-up After Diagnosis

• Annual monitoring for diabetes complications should begin 5 years after CFRD diagnosis. 1
• Patients with CFRD should be treated with insulin to attain individualized glycemic goals. 1

Common Pitfalls to Avoid

• Do not rely on A1C alone for screening—it will miss cases due to low sensitivity. 1, 2
• Do not use fasting glucose as the sole screening method—it is insufficient. 6
• Do not delay screening until adulthood—20% of adolescents already have CFRD. 1, 2
• Do not ignore weight changes—weight loss or failure to gain weight warrants immediate screening regardless of age. 1, 2