Insulin production and resistance in cystic fibrosis: effect of age, disease activity, and genotype.

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: One hundred and nineteen 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 were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic ß-cell function. All patients underwent an oral glucose tolerance test, 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. HOMAIR 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 agegroup, and to the HOMA-IR and 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, ß-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.

[Thirty years of activity at the center for cystic fibrosis in Parma]. / Trenta anni di attività del Centro per la fibrosi cistica di Parma.

One hundred fourteen patients (52 males, age range 1 to 40 yr, median age 16 yr) affected by Cystic Fibrosis (CF) are currently followed by the CF Centre of Parma. Forty two percent of them are adults. Most patients live in Emilia Romagna (59%) and Lombardia (19%). With respect to CF genotype, delta F508 mutation has been found in 54% of patients. Despite of the improvement in knowledge of CF, its diagnosis is still based on the clinical features and sweat test is usually used to confirm the diagnosis. Recent diagnostic tools, such as the genetic analysis and the potential difference measurement, could also be helpful in ambiguous situations. In the CF Centre of Parma, in agreement with the literature, the disease is now diagnosed earlier than in the past. Particularly, in the last year the median age of diagnosis was seven months, while it was 20 months in the 1980s. The early diagnosis and the improvement in the treatment of lung disease has significantly increased the median survival age of our patients, changing from 7.5 years in 1975 to 20 years in 1999. A significant improvement in CF prognosis could be further achieved by potential investigational agents, such as "protein-repair" addressed to CFTR activation. However, the gold standard for CF therapy is represented by gene therapy, although it is not yet available.

[Efficacy of long-term total parenteral nutrition treatment in a case of postoperative fistula of the gastric fundus]. / Considerazioni sull'efficacia del trattamento con NPT di lunga durata in un caso di fistola postchirurgica del fondo gastrico.

The Authors report their experience about an unusual case of gastro fundic fistula arisen after a surgical procedure and successfully treated with long term N.P.T. The Authors describe the modality of the long term treatment, underlining the importance and efficacy of N.P.T. which represents an efficient alternative to surgery.