Insulin Therapy to Improve BMI in Cystic Fibrosis–Related Diabetes Without Fasting Hyperglycemia

Abstract

OBJECTIVECystic fibrosis–related diabetes (CFRD) without fasting hyperglycemia (CFRD FH−) is not associated with microvascular or macrovascular complications, leading to controversy about the need for treatment. The Cystic Fibrosis Related Diabetes Therapy (CFRDT) Trial sought to determine whether diabetes therapy improves BMI in these patients.RESEARCH DESIGN AND METHODSA three-arm multicenter randomized trial compared 1 year of therapy with premeal insulin aspart, repaglinide, or oral placebo in subjects with cystic fibrosis who had abnormal glucose tolerance.RESULTSOne hundred adult patients were enrolled. Eighty-one completed the study, including 61 with CFRD FH− and 20 with severly impaired glucose tolerance (IGT). During the year before therapy, BMI declined in all groups. Among the group with CFRD FH−, insulin-treated patients lost 0.30 ± 0.21 BMI units the year before therapy. After 1 year of insulin therapy, this pattern reversed, and they gained 0.39 ± 21 BMI units (P = 0.02). No significant change in the rate of BMI decline was seen in placebo-treated patients (P = 0.45). Repaglinide-treated patients had an initial significant BMI gain (0.53 ± 0.19 BMI units, P = 0.01), but this effect was not sustained. After 6 months of therapy they lost weight so that by 12 months there was no difference in the rate of BMI change during the study year compared with the year before (P = 0.33). Among patients with IGT, neither insulin nor repaglinide affected the rate of BMI decline. No significant differences were seen in the rate of lung function decline or the number of hospitalizations in any group.CONCLUSIONSInsulin therapy safely reversed chronic weight loss in patients with CFRD FH−.

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

“…Mozillo et al18 found a significant increase in BMI only in patients with initial BMI Z-score <-1. Although Moran et al15 identify improvements in BMI in the group as a whole, in particular IGT group they did not notice a significant increase in this parameter. Dobson et al,6 Drummond et al,12 and Hameed et al19 chose to assess body weight.…”

“…Dobson et al6 showed an apparent increase in this parameter with the use of insulin, as it was only a case report. In studies by Moran et al,15 Drummond et al12 and Minicucci et al,16 FEV1 remained unchanged after the intervention. But Drummond et al12 evaluated separately only patients diagnosed with IGT and found a significant reduction in FEV1 decline rate in patients using insulin.…”

“…- 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.…”

“…Three studies used control groups to compare the effects of insulin. Moran et al15 selected corresponding controls who underwent other types of intervention (repaglinide or placebo), while Minicucci et al16 used controls with IGT and Koloušková et al17 used controls with normal OGTT by ADA criteria (NGT). In these last two studies, controls did not undergo pharmacological interventions.…”

“…Minicucci et al16 included patients with at least one of the following conditions: (I) body mass index BMI<10th percentile (p 10 ); (II) loss of one BMI percentile for age and sex in the previous year; (III) forced expiratory volume in one second (FEV1) ≤80% of predicted; and (IV) decreased FEV1≥10% in the previous year. Lung function deterioration and weight loss were also criteria for inclusion of subjects in the study by Dobson et al6 In contrast, Moran et al15 chose to intervene in a more clinically stable group of patients and used the following inclusion criteria: (I) end of linear growth; (II) weight stability in the last three months; (III) absence of acute infection in the last two months. Exclusion criteria for this study were: (I) use of oral or intravenous corticosteroids in the last six months; (II) fasting hyperglycemia in the previous year; (III) liver dysfunction; (IV) pregnancy.…”