EFFECT OF EARLY DERANGEMENTS IN GLUCOSE TOLERANCE MECHANISMS ON THE NUTRITIONAL STATUS AND RESPIRATORY FUNCTION OF CYSTIC FIBROSIS PATIENTS

The effects of early derangements in glucose tolerance mechanisms on the nutritional status and respiratory function of Cystic Fibrosis patients are currently investigated. Starting from year 2003 patients who received routinely OGTT at the regional Cystic Fibrosis center of Milan were followed prospectively. The OGTT at recruitment was analysed for glucose tolerance and insulin secretory (beta cell glucose sensitivity) and insulin sensitivity parameters derived from modelling of glucose, insulin and c-peptide profiles. One hundred-thyrty five patients aged 8-31 yr (mean age 16.9±0.4yr) were followed for 590 patient-years (median length of follow-up 4.5 years) and their weight, height and BMI z-scores were evaluated at entry and at end follow-up, with the FEV1 % values during the observation period. These data were related to the insulin secretory and insulin sensitivity parameters evaluated at entry. Twenty healthy subjects with a comparable age and sex distribution received a similar OGTT protocol and served as controls. Height z-score at entry was –0.6±0.1 in the subjects before puberty and turned to –0.8±0.1 at end follow-up (p=n.s) whereas weight z-score in all subjects was–0.5±0.1 at entry and turned –0.9±0.1 (p<0.001) at end follow-up. Beta-cell glucose sensitivity was reduced in CF compared to controls (70.0±4.1 vs 117.9±11.6 pmol min-1 m-2 mM-1, p>0.001) whereas insulin sensitivity was almost superimposable. Beta-cell glucose sensitivity was weakly but significantly related to weight z-score both at entry (r2=0.043, p<0.01)and at end follow-up (r2=0.048, p<0.01), whereas insulin sensitivity was not. In contrast, height z-score was significantly and inversely related to insulin sensitivity, both at entry and end follow-up(p<0.05). In addition, beta cell function was significantly related to FEV1 percent in each of the subsequent years of follow-up (p<0.01) but not to the rate of FEV1 decline during the whole observation period. In conclusion, beta cell function defects are significantly related to respiratory defects and to weight reduction over a subsequent four years period. However also insulin sensitivity defects are involved, and can be shown in relationship to statural growth defects