Insulin Production and Resistance in CF: Effect of Age, Disease Activity and Genotype

J Endocrinol Invest. 2011 Apr 6. [Epub ahead of print]

INSULIN PRODUCTION AND RESISTANCE IN CYSTIC FIBROSIS: EFFECT OF AGE, DISEASE ACTIVITY, AND GENOTYPE.

Street ME, Spaggiari C, Ziveri MA, Rossi M, Volta C, Viani I, Grzincich GL, Sartori C, Zanzucchi M, Raia V, Terzi C, Pisi G, Zanetti E, Boguszewski MC, Kamoi TO, Bernasconi S.

Department of Paediatrics, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy.

Abstract

Aim: To assess the major determinants of glucose tolerance between age, genotype and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF related diabetes (CFRD). Subjects and Methods: 119 patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age also were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. HOMA-IR, fasting glucose/insulin ratio(FGIR) were calculated as indices of insulin resistance and insulinogenic index as a marker of pancreatic β cell function. All patients underwent an OGTT, and 57 underwent an IVGTT for the calculation of first phase(FPIR) and acute insulin responses(AIR).

 Results:The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMA-IR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses glucose tolerance was related to the age-group, and to the HOMA-IR ans insulinogenic indexes. Conclusions: IGT and CFRD were related mainly to genotype, although as expected the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, β-cell function and reduced insulin sensitivity to the onset of CFRD, however further studies are warranted to better elucidate this aspect.