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Eight male patients with cystic fibrosis, normal nutrition, normal physical activity, relatively mild pulmonary disease, no evidence of liver disease and no family history of diabetes mellitus underwent a series of carbohydrate tolerance tests in comparison with a group of 18 normal male subjects matched for age and body weight. Compared with the normal group, the patients with cystic fibrosis had significantly impaired glucose tolerance and significantly lower serum immunoreactive insulin levels during oral and intravenous glucose tolerance tests; serum insulin levels were also significantly lower after intravenous administration of tolbutamide in the patients with cystic fibrosis, but the reduction in blood glucose concentration in each group was not significantly different. During an intravenous insulin test, the decrease in blood glucose concentration was the same for both groups, in spite of significantly lower serum insulin levels in the patients with cystic fibrosis .The percentage fall in plasma free fatty acids was at least as great in the patients with cystic fibrosis as in normals during the test procedures; while a significant decrease in plasma alpha-amino nitrogen after intravenously administered insulin was seen only in the patients with cystic fibrosis. These studies suggest that the carbohydrate intolerance of cystic fibrosis is consequent upon an impaired insulin response to glucose, but that this insulin deficiency is partly compensated for by increased peripheral tissue sensitivity to insulin.
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PMID:Endogenous and exogenous insulin responses in patients with cystic fibrosis. 111 Aug 65

Early insulin response to rapid intravenous injection of glucose was studied in 7 cases of cystic fibrosis aged 8 months to 9 1/2 years. Plasma insulin was measured with a radioimmunological method. Blood glucose values were determined and the glucose disappearance rate (kG) calculated. In all children except the youngest one the early insulin response values were low compared with normal children. The kG-values were normal and correlated neither to the duration of clinical symptoms, nor to the patients' actual clinical condition measured by means of the Shwachman score. The explanation of the decreased insulin response is probably the progressive fibrosis of the pancreas. This may also explain the reported increased incidence of diabetes mellitus in cystic fibrosis. Comparison is made with the condition in pancreatic fibrosis in rabbits, produced through duct ligation.
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PMID:Insulin release in cystic fibrosis. 114 52

Adult patients with cystic fibrosis (CF) are at high risk for developing insulin-dependent diabetes mellitus. Therefore, the fast insulin release (FIR) to intravenously administered glucose was measured in 23 adult CF patients. The influence of the clinical parameters and type of gene deletion on the amplitude of the FIR, defined by the sum of the 1st- and 3rd-minute insulin concentrations was analyzed. In 11 of the 18 normoglycemic patients with exocrine pancreatic insufficiency and the 3 nontreated diabetic CF patients studied, an FIR value lower than the 3rd percentile was found. The female patients had higher mean FIR values than the male patients (62.8 +/- 39.6 vs. 27.9 +/- 17.9 mU/l; p < 0.05). No influence of age, body mass index, or pulmonary or liver involvement on the FIR was found. Subjects heterozygous for the delta F508 deletion had a similar insulin response as homozygous patients. The FIR level correlated negatively with the basal glucose level (r = 0.4; p < 0.001). In conclusion, 61% of the adult nondiabetic CF patients with exocrine pancreatic insufficiency presented a loss in acute insulin response, which could not be predicted by clinical or genetic parameters.
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PMID:First-phase insulin release in adult cystic fibrosis patients: correlation with clinical and biological parameters. 130 48

Between September, 1984, and March, 1991, 79 patients underwent heart-lung transplantation for end-stage cystic fibrosis at the Harefield Hospital. Short-term outcome has already been reported, and we now present intermediate-term results. The overall actuarial patient survival was 69% at 1 year, 52% at 2 years, and 49% at 3 years. 17 patients had diabetes mellitus with a survival of 62% to 1 year and 51% to 2 years. 23 patients had one or more other possible high-risk factors, and survival of these patients was 64% at 1 year and 57% at 2 years, compared with 71% and 49%, respectively, in the low-risk group (n = 56). Pseudomonas aeruginosa infection was the most common respiratory infection encountered postoperatively. 92% of patients had at least one episode of acute rejection during the first 3 postoperative months. Lung function was greatly improved after transplantation, the mean forced expiratory volume in 1 s and forced vital capacity increasing from 22% and 35% predicted, respectively, preoperatively to 68% and 70% predicted, respectively, by the sixth postoperative month. This improvement was maintained at 1, 2, and 3 years after transplantation. Lymphoproliferative disorders (4 patients) were successfully treated. Obliterative bronchiolitis developed in 17 patients and the cumulative probability of getting this complication at 1, 2, and 3 years postoperatively was 17%, 23%, and 48%, respectively. Overall, 7 patients were retransplanted. There was no coronary artery disease in the 37 patients who underwent coronary angiography at 1 year, 14 at 2 years, and 9 at 3 years after surgery. 58 patients donated their hearts for subsequent "domino" heart transplantation. Our 5 1/2-year experience with heart-lung transplantation is encouraging but the shortage of donor organs and the complication of obliterative bronchiolitis are the two main obstacles to be overcome.
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PMID:Intermediate-term results of heart-lung transplantation for cystic fibrosis. 135 59

The impact of pre-diabetes on clinical status was retrospectively studied in 38 cystic fibrosis (CF) patients with diabetes mellitus (DM) and 38 non-diabetic CF patients (control patients), matched in pairs for age, sex, and chronic Pseudomonas aeruginosa lung infection. Quarterly parameters of CF clinical status were collected for 6 years prior to the diagnosis of DM in the index case. Compared to the control patients, decreases in body weight, body mass index (BMI), forced expiratory volume in 1s (FEV1), and forced vital capacity (FVC) and an increase in the daily intake of pancreatic enzyme capsules were found in the pre-diabetic patients. Statistically significant differences in body weight, BMI, FEV1, FVC, and intake of pancreatic enzyme capsules between pre-diabetic and control patients emerged 4, 4, 1.25, 3 and 4.5 years prior to the diagnosis of DM, respectively. The number of lung infections did not differ between the two groups of patients. Thus, when DM develops in CF patients, an insidious decline in overall clinical status is observed for years prior to its diagnosis. Whether clinical deterioration in CF leads to DM, or pre-diabetes results in declining CF clinical status is presently unknown. Accumulating evidence suggests that the latter may be the case since insulin therapy seems to improve lung function in CF.
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PMID:Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. 139 31

Mental disorders affect 18% to 20% of children and adolescents. The rate in children with chronic illness is probably higher. This study of chronically ill children addresses the discrepancy between parent and child reports of child psychiatric disorders and the extent to which pediatricians agree with reports by children and parents regarding such problems. Eighty-three subjects, aged 9 to 18 (mean = 12.6), were recruited; they had the following diagnoses: cystic fibrosis, diabetes, inflammatory bowel disease, and cancer. Subjects and one parent were interviewed separately, using the Diagnostic Interview Schedule for Children (DISC-2.1). The subject's physician completed a questionnaire asking about the presence of a range of mental disorders. Forty-one (49%) subjects reached threshold criteria for a psychiatric diagnosis, using both parent and child as informants. Psychiatric disorders were identified in only 22 subjects (54%) by the child and in 28 (68%) by parent alone. Thus, reliance on one informant resulted in failure to identify one third to one half of psychiatric disorders. Physicians' ratings agreed significantly with children's reports but not with parental reports, suggesting that physicians are sensitive to children's concerns but may underestimate the value and importance of parents' reports. Clinical and research evaluations of chronically ill children, as well as clinician identification of mental health problems, will be influenced by the choice of informant.
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PMID:Mental disorders in chronically ill children: parent-child discrepancy and physician identification. 140 41

There is a high prevalence of diabetes mellitus in patients with CF and this is likely to increase in the future as more patients are surviving into adult life. In view of this all CF clinics should routinely screen for diabetes mellitus. The prevalence of diabetes mellitus in adult CF patients is higher than in children, and the onset is commonly insidious. The diabetes seen in CF is not classical Type 1 diabetes or Type 2 diabetes and could more helpfully be called cystic fibrosis-related diabetes (CFRD). Treatment is by oral hypoglycaemic agents or insulin. It is not appropriate to control patients by diet alone. Dietary advice to CF diabetic patients is not the same as that given to non-CF diabetic patients. Microvascular complications have now been reported and careful monitoring of all CF patients with diabetes should be undertaken.
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PMID:Diabetes mellitus and cystic fibrosis. 144 69

Differences in the lipid composition of human milk have been described in maternal diseases known to affect fat metabolism. Diseases such as diabetes, cystic fibrosis, hypobetalipoproteinemia and Type I hyperlipoproteinemia affect the quantity and quality of human milk fat. Increased fatty acid chain elongation and changes in desaturation (especially delta 6 desaturase), as well as changes in lipid class composition, have been shown in diabetes and cystic fibrosis, whereas compensatory increases in medium-chain fatty acids have been described in hypobetalipoproteinemia and Type I hyperlipoproteinemia. It is important to realize that these observations were made either on single women or on very small groups of women. In infant diseases, such as breast milk jaundice and ectopic eczema, changes in polyunsaturated fatty acids in maternal milk have been described.
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PMID:Human milk in disease: lipid composition. 149 2

Glucose tolerance has been assessed in cystic fibrosis (CF) children using HbA1C and plasma glucose and insulin determinations during an oral glucose tolerance test (OGTT), along with the determination of HLA-DR and islet-cell (ICA) and anti-insulin (IAA) antibodies. Of 49 patients (25 males, 24 females), aged 2 to 21 years (mean = 10.9 years), 29 had normal glucose tolerance (WHO criteria) during OGTT, 14 had impaired glucose tolerance (IGT) and 6 had an isolated hyperglycemia at 120 min. Fasting plasma glucose and HbA1C were significantly higher in IGT than in normoglycemic patients. However, these two parameters showed poor individual predictive value of disturbance in glucose tolerance. Of 14 patients with abnormal OGTT, 7 were aged below 10 years, with 2 as young as 5 years; 8 patients were females. HLA antigens characteristic of type I diabetes tended to be found less frequently in CF patients than in the general population: 9% were DR3, 7% were DR4 and none was DR3/DR4. There were no HLA differences according to glucose tolerance. ICA and IAA were respectively detected in only one patient. Stimulated plasma insulin was low but did not correlate with glucose tolerance. In conclusion, impaired glucose tolerance is common in cystic fibrosis and can be found early in life. Although insulin secretion is decreased in this population, it does not seem to be the only factor responsible for impaired glucose intolerance. The absence of the genetical and immunological characteristics of type I diabetes confirms that glucose intolerance in cystic fibrosis is due to other pathogenetic mechanisms.
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PMID:[Research of factors for glucose intolerance in mucoviscidosis]. 155 Apr 46

Assessed patterns of stress in families of children with pediatric conditions that varied on 2 dimensions: (a) fatal vs. nonfatal outcome and (b) presence vs. absence of cognitive impairment. Families of children with cystic fibrosis (n = 23), diabetes (n = 24), and moderate mental retardation (n = 24) were compared to families of well children (n = 24) in 3 age groups. Maternal responses to a multidimensional measure of family stress, the Questionnaire on Resources and Stress--Short Form (QRS-S), indicated that families of children with chronic conditions did not differ from families of well children on scales assessing generic aspects of family stress, such as family conflict. However, diagnostic groups differed on QRS-S scales assessing stressors specific to the child's disability (e.g., families of children with mental retardation were characterized by concerns about caring for the child as an adult). There was no evidence of higher levels of stress for families of older children. Data on the internal consistency of QRS-S scales and their relation to measures of maternal and child adjustment are presented.
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PMID:Family resources and stress: a comparison of families of children with cystic fibrosis, diabetes, and mental retardation. 164 Mar 16


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