Incidence and prevalence of cystic fibrosis–related diabetes (CFRD) are rapidly increasing in recent years, according to the gradual increase in median survival age, which is now around 30 years (1). CFRD, with or without fasting hyperglycemia, may be chronic or intermittent, the latter in physically stressed patients. It is possible that the prediabetic state may have adverse effects on clinical status, nutrition, and lung function in patients with cystic fibrosis (2). As a matter of fact, impairment of lung function seems to appear up to 2–4 years before the clinical onset of diabetes. Insulin therapy was able to improve lung function in CFRD patients (3). Glargine is a recent long-acting insulin analog, which is a good candidate for basal insulinization, owing to a duration of action of 24 h without any peak and any hypoglycemic effect. Therefore, we speculated whether glargine treatment could exert beneficial effects in chronic or intermittent CFRD patients.
We analyzed eight CFRD patients (six females), aged 10–29 years, who were affected by pancreatic exocrine deficiency, had mean forced expiratory volume in 1 s (FEV1) of 77% (range 62–104), and were treated for 6 months with glargine. Four of eight patients were homozygous for the ΔF-508 mutation, two were heterozygous, one had a different CFTR mutation, and one was negative for known mutations. Patients were divided in two groups: Group A comprised four patients with chronic CFRD (three females, aged 15–29 years) treated with rapid insulin (0.9 units · kg−1 · day−1) in two or three doses in the last 1–3 years. Group B included four patients with intermittent CFRD (three females, aged 10–21 years) requiring insulin only during infections. Glargine was administered at 0.3 units · kg−1 · day−1 in all patients once a day. Group A patients continued their preprandial rapid insulin administrations besides glargine. At the end of the study, BMI, FEV1 percentage, HbA1c (A1C), and the number of lung infections were compared with baseline values. The control group comprised six patients with intermittent CFRD (four females, aged 14–18 years) who were affected by pancreatic exocrine deficiency and had a mean FEV1 of 71.8% (range 47–100); three of the patients were homozygous for the ΔF-508 mutation and three were heterozygous. All glargine-treated patients showed a good compliance with therapy; no hypoglycemic crises were recorded. The number of lung infections decreased in group A from 3.75 ± 0.5 to 1.75 ± 0.9 (P < 0.01) and in group B from 2.75 ± 0.50 to 1.25 ± 0.5 (P < 0.001), while no change was found in A1C and BMI. Moreover, the total dose of daily insulin did not change in group A. In the control group, the number of lung infections did not change during the same period of observation (3.3 ± 1.2 vs. 3.1 ± 0.4).
Our preliminary experience suggests that basal insulinization obtained not only in overt diabetic cystic fibrosis patients but also in prediabetic cystic fibrosis patients may play a pivotal role in reducing the number of lung infections. No hypoglycemic event occurred also in prediabetic patients, suggesting that—regardless of their fasting euglycemic status—they probably already required moderate basal insulin doses. The period of observation was probably too short to detect any positive change in BMI, FEV1, or any other health parameters. Further controlled studies should be encouraged in order to confirm the possible effects of glargine in preventing lung function impairment in cystic fibrosis patients.
