Glucose Tolerance, Insulin Secretion, and Insulin Sensitivity in Children and Adolescents with Cystic Fibrosis and No Prior History of Diabetes

Elder, Deborah A.; Wooldridge, Jamie L.; Dolan, Lawrence M.; D’Alessio, David A.

doi:10.1016/j.jpeds.2007.05.012

Cited by 48 publications

(46 citation statements)

References 33 publications

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“…However, quantitative aspects may not be comparable (8,37,40,46). The largest available adult series (37) displayed an average b-cell function as 70% of control values in the whole CF population and 50% of control values in the subgroup with NGT.…”

Section: Discussionmentioning

confidence: 97%

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Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Battezzati

Mari

Zazzeron

et al. 2011

European Journal of Endocrinology

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Background: Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance. Aim: To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population. Methods: A total of 165 CF subjects (80 females) aged 17G5 years and 18 age-and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas b-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration. Results: Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. b-cell function was reduced in CF patients compared with CON (70.0G4.1 vs 117.9G11.6 pmol/min per m 2 per mM, P!0.001) and decreased significantly with age by K2.7 pmol/min per m 2 per mM per year (confidence interval (CI) K4.5 to K0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower b-cell function and higher insulin sensitivity. Conclusion: The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining b-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

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Section: Discussionmentioning

confidence: 97%

“…These may be related to increased glucose production and gluconeogenesis during fasting (34,35). Heterogeneous data on insulin sensitivity spanning from increased (36), normal (37,38), and decreased (11,39,40) insulin sensitivity were obtained similarly using surrogate techniques.…”

Section: Introductionmentioning

confidence: 99%

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Battezzati

Mari

Zazzeron

et al. 2011

European Journal of Endocrinology

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“…As opposed to children without cystic fibrosis (CF), young individuals with CF are frequently affected by an abnormal glucose metabolism [1,2]. This, and its progression towards a CF-related diabetes (CFRD) is due to reduced or delayed insulin secretion, combined with insulin resistance [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

“…This, and its progression towards a CF-related diabetes (CFRD) is due to reduced or delayed insulin secretion, combined with insulin resistance [1,3,4]. Worsening of glucose metabolism leads to increased bacterial growth in the lungs and thus infections of the airways, which limit lung function and life expectancy [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function

Terliesner¹,

Vogel

Steighardt³

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents. Methods: A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient. Results: SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both p < 0.05) but years before the evidence of diabetes. Afterwards there was a significant decline in height (p < 0.001) and weight (p < 0.01) SDS in CFRD patients and an increasing difference between the height and weight of CF patients with or without diabetes. In contrast, no significant reduction of BMI-SDS was observed in CFRD patients. All analysed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to the diagnosis of diabetes. Conclusions: Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.

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“…Similar to our findings, other studies found no significant differences between glucose tolerance and nutrition. 1,13,34,35 In the pediatric and adult CF program at Hospital de Clínicas de Porto Alegre, patients are monitored by a nutritionist. The dietary management of CFrelated diabetes maintains a high-energy-content diet and patients are advised not to limit their intake of carbohydrates, high-fat foods, or proteins.…”

Section: Discussionmentioning

confidence: 99%

Glucose Intolerance in Patients With Cystic Fibrosis: Sex-Based Differences in Clinical Score, Pulmonary Function, Radiograph Score, and 6-Minute Walk Test

et al. 2011

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OBJECTIVE:To determine the sex-specific relationships between glucose intolerance and Shwachman-Kulczycki clinical score, lung function, Brasfield chest-radiograph score, and exercise capacity in patients with cystic fibrosis (CF). METHODS: We used a cross-sectional study design and included CF patients > 10 years old. All patients had clinical and nutritional evaluation, oral glucose tolerance test, spirometry, chest radiograph, and 6-min walk test (6MWT). Patients were classified as having normal glucose tolerance, impaired glucose tolerance, or CF-related diabetes mellitus. RESULTS: We included 88 patients: 59 with normal glucose tolerance, 15 with impaired glucose tolerance, and 14 with CF-related diabetes. Shwachman-Kulczycki clinical score (P ‫؍‬ .04), at-rest S pO 2 (P ‫؍‬ .001), S pO 2 difference before versus after 6MWT (P ‫؍‬ .001), and Brasfield chest-radiograph score (P ‫؍‬ .01) were significantly lower in the impaired-glucose-tolerance group than in the normal-glucosetolerance group, but did not differ from the CF-related-diabetes group. In female patients only, percentof-predicted FEV 1 was significantly lower in the impaired-glucose-tolerance group than in the normalglucose-tolerance group (P ‫؍‬ .02), but did not differ from the CF-related-diabetes group (P ‫؍‬ .10). There was a significant relationship between glucose intolerance and sex when clinical score, 6-min walk distance, FEV 1 , and radiograph score were combined in a multivariate analysis. CONCLUSIONS: In patients with CF, glucose intolerance was associated with poor clinical score, lower at-rest S pO 2 , greater S pO 2 difference before versus after 6MWT, poor lung function, and lower radiograph score. Overall, multivariate analysis indicated poorer performance in the latter variables in female patients with glucose intolerance than in male patients with glucose intolerance.

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Glucose Tolerance, Insulin Secretion, and Insulin Sensitivity in Children and Adolescents with Cystic Fibrosis and No Prior History of Diabetes

Cited by 48 publications

References 33 publications

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function

Glucose Intolerance in Patients With Cystic Fibrosis: Sex-Based Differences in Clinical Score, Pulmonary Function, Radiograph Score, and 6-Minute Walk Test

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