Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance

Abstract

Diabetes mellitus is an increasing complication of cystic fibrosis (CF), as a result of the improved life expectancy. There is clear association between diabetes and increased morbidity and mortality. Lung function and clinical status deteriorate up to 2-4 yr before the diagnosis of CF-related diabetes (CFRD). The aim of our study was to evaluate the effects, on glucose homeostasis and clinical status, of the early treatment with insulin glargine in CF patients with impaired glucose tolerance (IGT). We selected six subjects with IGT diagnosed at oral glucose tolerance test (OGTT). Median age was 18.12 yr (range 9.2-27.8). Insulin glargine was administered at the median dosage of 0.3 U/kg/day (range 0.2-0.5). After the initial adjustment of the dosage, no patient manifested hypoglycemia during treatment. Median glycosylated hemoglobin (HbA1c) did not show any significant variation during treatment: it was 5.9% at baseline (range 5.5-6.2) and 6.1% (range 5.0-6.7) at the end of follow-up (p=0.496). Median body mass index (BMI) z-score significantly increased during treatment, from -0.95 (range -3.2-+0.6) at baseline to -0.5. (range -3.0-+0.9) at the end of follow-up (p=0.026). Lung function, measured by median forced expiratory volume in the first second (FEV1%), showed a mild but significant improvement during insulin treatment. It was 72.7% at baseline (range 41.5-98.4) and 76.7% (range 42.0-106.8) at the end of follow-up (p=0.027). No significant variation was found between the number of hospitalizations for clinical exacerbation (no./patient/yr) in the last 2 yr before treatment and during follow-up. Median number at baseline was 1.95/patient/yr (range 1-3) and 2.0/patient/yr (range 1-3) at follow-up (p=0.715). Our data seem to indicate that early insulin therapy can be safe, no patient manifested hypoglycemia or other adverse effects during treatment. Insulin is an anabolic hormone implicated in both lipid and protein metabolism. The appearance of IGT out of infections can indicate an early insulin deficiency, with a potential impact on the nutritional and clinical status of the patient, even before the appearance of overt diabetes. Larger controlled trials are necessary to verify if early insulin therapy is able to reduce the deterioration of nutritional status and lung function associated with the onset of IGT.

Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

“…However, in the study by Minicucci et al16 there was a 10% decrease in FEV1 in the year prior to the intervention, which may be a bias because even CFRD patients have no such decline in this parameter. Koloušková et al17 and Drummond et al12 , who had a more consistent number of cases, found that FEV1 was lower in the untreated group compared to those treated with insulin, which confirms the results described by Dobson et al6 Bizarri et al20 , and Hameed et al19 …”

“…The authors assumed that participation in the study made patients more aware of their change in glucose metabolism, leading to better nutritional behavior. Most other studies6 , 17 - 20 showed positive results, but the insulin doses used were higher.…”

“…Bizzarri et al,20 Mozzillo et al,18 and Hameed et al19 found a significant increase in FEV1 after the use of insulin. Koloušková et al17 found that, at the end of follow-up, intervention group had higher FEV1 compared to control group.…”

“…- 18 , 20 Bizzarri et al,20 Moran et al,15 and Koloušková et al17 demonstrated a significant increase in BMI after insulin intervention. Mozillo et al18 found a significant increase in BMI only in patients with initial BMI Z-score <-1.…”

Cystic fibrosis related diabetes—a new perspective on the optimal management of postprandial glycemia

“…Moreover, there is now persuasive evidence that the decline in nutritional and pulmonary status occurs 2-6 years before the diagnosis of CFRD, when postprandial hyperglycaemia is less marked [5,6]. This suggests that even 'early' carbohydrate intolerance, with relatively modest postprandial glycaemic excursions, is metabolically detrimental to pulmonary function.…”