RESUMO
OBJECTIVES: We conducted a 1-year randomized controlled trial to test the hypothesis that growth hormone (GH) improves the clinical status of children with cystic fibrosis. STUDY DESIGN: Nineteen prepubertal children were randomized to control (NonTX, n = 9) or to daily injections of GH (0.3 mg/kg/wk) (GHTX, n = 10) for 1 year. Every 3 months height, weight, and lean tissue mass were measured. Caloric intake, resting energy expenditure, pulmonary function, and respiratory muscle strength were measured every 6 months, as were total number of hospitalizations and courses of outpatient intravenous antibiotics. RESULTS: The GHTX group had significantly greater height, height velocity (NonTX = 3.8 +/- 1.4 cm/y, GHTX = 8.1 +/- 2.4 cm/y; P =.002), weight, weight velocity (NonTX = 2.1 +/- 0.9 kg/y, GHTX = 4.5 +/- 1.1 kg/y; P =.004), and change in lean tissue mass (NonTX = 2.1 +/- 1.6 kg, GHTX = 4.7 +/- 1.7 kg; P =.01) analyzed by the Student t test. The GHTX group had significant improvement in delta forced vital capacity compared with the year before study, and respiratory muscle strength improved. The number of hospitalizations and outpatient intravenous antibiotic courses significantly decreased in the GHTX group but did not change in the NonTX group. No subject had development of cystic fibrosis-related diabetes. CONCLUSIONS: Results of the first randomized controlled trial of GH treatment in cystic fibrosis indicate that GH improves growth and clinical status.
Assuntos
Fibrose Cística/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Composição Corporal , Estatura , Peso Corporal , Criança , Fibrose Cística/fisiopatologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Testes de Função RespiratóriaRESUMO
Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patients was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m2 per minute). Results from the 120 mU/m2 per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 +/- 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 +/- 1.1, patients with CF = 10.2 +/- 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance (r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes.
Assuntos
Fibrose Cística/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Adulto , Glicemia , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Genótipo , Teste de Tolerância a Glucose , Humanos , MasculinoRESUMO
Seven patients with cystic fibrosis who had complications of gastroesophageal reflux including abdominal pain, peptic esophagitis, upper gastrointestinal hemorrhage, and esophageal stricture are described. We believe that these are gastrointestinal complications of CF and that they may be responsible for significant morbidity. The mechanical influence of a depressed diaphragm caused by hyperinflation, along with increased abdominal pressure with chronic coughing, may contribute to GER in CF. Early detection and treatment are important not only to prevent esophageal complications but also to increase the quality of life by relief of pain and by avoiding the resultant decrease in appetite, which can contribute to malnutrition.