Scoping review: relationship between glucose tolerance and pulmonary decline in cystic fibrosis

Cystic fibrosis-related diabetes (CFRD) causes deterioration of cystic fibrosis (CF) lung disease, thereby increasing mortality. Lung function decline occurs at glycemic levels below current CFRD diagnostic thresholds. CFRD may be better defined by examining the relationship between lung function decline and elevated glucose levels in individuals without diabetes. This scoping review examines the existing literature on the relationship between oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) values, and percent predicted forced expiratory volume in one second (%FEV1) and forced vital capacity (FVC) to determine whether alternative glucose levels would be more appropriate for defining CFRD based on lung function decline. Electronic database searches were performed on Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials in June 2023. Studies that assessed glucose levels from glucose tolerance test (GTT) and/or CGM and their relationship to %FEV1 and FVC were included. A total of 10 studies were included. For OGTT, three studies found that one-hour OGTT plasma glucose levels > 11.0 mmol/L were inversely associated with %FEV1. Two studies found that peak GTT levels were inversely associated with %FEV1. For CGM, four studies found inverse associations between %FEV1 and percent predicted forced vital capacity (%FVC) and the number of glucose measurements ≥ 11.0 mmol/L, the percentage of time spent with glucose > 7.8 mmol/L, or the area under the curve > 7.8 mmol/L. Intermediate OGTT values and CGM metrics are associated with lung function decline in CF without diabetes. Correlations between CGM and OGTT values need to be established. Prospective studies are required to determine whether treating elevated intermediate OGTT values can prevent lung function decline before revising CFRD diagnostic criteria.