Elevation of 1-Hour Plasma Glucose During Oral Glucose Tolerance Testing Is Associated With Worse Pulmonary Function in Cystic Fibrosis

Abstract

OBJECTIVECystic fibrosis (CF)-related diabetes (CFRD) is associated with declining pulmonary function and increased mortality. During oral glucose tolerance testing (OGTT), CFRD is defined by 2-h plasma glucose (PG2). We hypothesized PG elevations during OGTT resolving by 2 h, not meeting CFRD criteria, influence pulmonary function in CF. Thus we investigated the frequency of elevated 1-h OGTT PG (PG1) and its relationship with pulmonary function.RESEARCH DESIGN AND METHODSRetrospective review of OGTTs was performed between August 2005 (annual screening initiation) and June 2008 at Children’s Hospital of Philadelphia CF Center. First-time, well state OGTTs (PG0, PG1, PG2) were analyzed. Additional data collected were: percent predicted forced expiratory volume in 1 s (FEV1), BMI percentile, lung bacterial colonization, age, and sex. OGTTs were categorized as normal (PG2 <140 mg/dL), impaired glucose tolerance (IGT) (PG2 140–199 mg/dL), CFRD (PG2 ≥200 mg/dL), and indeterminate glycemia (INDET) (PG1 ≥200 mg/dL and PG2 <140 mg/dL). Frequency of PG1 ≥140 but <200 mg/dL was also noted. Multivariable linear regression was used to assess associations between percent predicted FEV1, BMI percentile, and OGTT PG.RESULTSOGTTs (101) were available (59 male/42 female; age 5.8–22 years, percent predicted FEV1 = 94.5 ± 18%, BMI percentile = 52 ± 25%). With the use of PG2, 91 OGTT were normal, eight were IGT, and two were CFRD. With the use of PG1 (n = 89), 39 OGTT were normal, 36 were PG1 ≥140 <200 mg/dL, and 14 were PG1 ≥200 mg/dL. PG1 was negatively associated with percent predicted FEV1, adjusting for BMI percentile (P = 0.009, R2 0.13). Percent predicted FEV1 was not associated with PG0, PG2, age, sex, or lung bacterial colonization.CONCLUSIONSPG elevations at nontraditional OGTT times are common in CF. The association of increasing PG1 with worse pulmonary function suggests early PG abnormalities may be deleterious or an early marker for worsening disease and will be missed if CFRD diagnosis focuses on PG2.

Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function

“…This can be explained by the parallel decrease in weight as well as height scores. Previous studies have related the development of CFRD to deterioration in lung function [23][24][25]. This relation is confirmed by our results.…”

Prevalence and Predictors of Diabetes After Lung Transplantation: A Prospective, Longitudinal Study

“…We have previously shown that bronchiolitis obliterans syndrome is the main cause of death after LTx, irrespective of DM status (8). DM may directly impair lung function in LTRs, as it does in the general population (30,31), and in patients with CF (32,33). Supporting a lung-related mechanism of mortality are the ISHLT reports of donor DM conferring a significantly increased risk of 1-year mortality (2,34), since lungs from donors with DM may already have changes predisposing to graft dysfunction or fibrosis.…”

Screening for cystic fibrosis-related diabetes: a systematic review.

“…Brodsky et al 99 carried out OGTTs in 101 patients and found that isolated 1-hour hyperglycaemia (i.e. with normal 2-hour levels) was associated with reduced FEV 1 , although numbers were few, with only nine patients in this group.…”