Infancy-Onset Cystic Fibrosis–Related Diabetes

Cystic fibrosis is a genetic disorder characterized by hyperviscous secretions and progressive obstructive end organ damage. Common presentations include meconium ileus, recurrent pulmonary infections, and failure to thrive. Although cystic fibrosis–related diabetes (CFRD) usually presents in the 2nd decade of life, it has been reported in children as young as 2 years (1). Here we present a 7-month-old infant who had CFRD at the time of presentation with cystic fibrosis.

A 7-month-old Caucasian male presented for evaluation of failure to thrive despite adequate intake of high-calorie formula. He was born at term but small for gestational age (birth weight <3rd percentile). Review of systems was significant for a chronic nonproductive cough, three to five loose bowel movements per day, and no history of polydipsia or polyuria. Random blood glucose obtained during a hospitalization for bronchiolitis at 4 months of age was normal. His only medication was multivitamin solution.

At 7 months of age, his weight and length were below the 3rd percentile. Laboratory studies revealed sodium 134 mmol/l (135–145), glucose 119 mg/dl, albumin 2.9 g/dl (3.1–4.7), and sweat chloride 105 mmol/l (0–40). A diagnosis of cystic fibrosis was made. Cystic fibrosis gene analysis revealed homozygous ΔF508 mutation.

Pancreatic elastase was <50 mcg EI/g stool (normal >200), consistent with exocrine insufficiency. Salt and pancreatic enzyme supplementations were introduced. Total parenteral nutrition (TPN) with glucose infusion rate of 9.7 mg · kg⁻¹ · min⁻¹ was initiated. The infant developed a marked hyperglycemia (250–559 mg/dl), persistent despite the discontinuation of TPN administration. HbA_1c (A1C) was 6.4% (4.0–5.9), and C-peptide 0.6 ng/ml (0.9–4.2) with blood glucose 215 mg/dl. GAD 65, islet cell antibodies (ICA 512), human insulin antibodies, and urinary ketones were negative. Subcutaneous insulin was initiated. The patient was discharged on insulin (0.35 units · kg⁻¹ · day⁻¹) and pancreatic enzyme supplementations and displayed excellent catch-up of linear growth (Fig. 1). At 24 months of age, he required 0.4 units · kg⁻¹ · day⁻¹ of insulin and had A1C of 8.7%.

While transient glucose intolerance associated with steroid administration in an infant with cystic fibrosis has been reported (2), to our knowledge our case represents the youngest patient with permanent CFRD ever described. The lack of autoimmunity, continued insulin requirements beyond the age of 18 months, later age at diagnosis, and absence of phenotypic abnormalities (3) effectively exclude type 1 diabetes and transient and permanent neonatal diabetes, respectively.

In conclusion, this case expands the clinical spectrum of CFRD and emphasizes the importance of aggressive nutritional therapy and insulin replacement. Although rare in this age-group, CFRD needs to be considered in clinically unstable children with cystic fibrosis and should be included in the differential diagnosis of non–type 1 diabetes of infancy.