Increased glucose excursion in cystic fibrosis and its association with a worse clinical status

Costa, Marcella Albaine Farias da; Potvin, Stéphanie; Hammana, I.; Malet, Arnaud; Berthiaume, Yves; Jeanneret, Alphonse; Lavoie, Annick; Lévesque, Renée; Perrier, Joëlle; Poisson, D; Karelis, Antony D.; Chiasson, Jean‐Louis; Rabasa‐Lhoret, Rémi

doi:10.1016/j.jcf.2007.02.005

Cited by 69 publications

(75 citation statements)

References 41 publications

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“…Alterations in glucose tolerance are characterized by marked glycemic peaks often followed by rapid normalization (11)(12)(13). Fasting glycemia is generally lower than in other forms of diabetes and fasting hypoglycemia has been reported (14).…”

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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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: 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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“…In the CF population, patients with and without CFRD all display significantly reduced insulin secretion [29]. There is mounting evidence that mutant CF Transmembrane Conductance regulator (CFTR), the CF disease-causing gene, is expressed in islet cells and is associated with abnormal cell function [30,31].…”

Section: Discussionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin type 9 affects insulin but not lipid metabolism in cystic fibrosis

Coriati

Arslanian

Bouvet

et al. 2017

CIM

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Proprotein Convertase Subtilisin/ Kexin type 9 affects insulin but not lipid metabolism in cystic fibrosis Abstract Purpose: Cystic Fibrosis (CF) is the most common genetic disorder and, with improved survival, glucose abnormalities have emerged as a major comorbidity. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of plasma LDL-cholesterol homeostasis, is associated with lipid and glucose metabolism in healthy individuals. Here we report on the link between PCSK9 and markers of metabolism in CF.Methods: Cross-sectional analysis was performed on CF patients (≥ 18 years, N=94) from the Montreal Cohort, without known diabetes, and on healthy individuals (N=19). The levels of PCSK9 and lipid markers were quantified and all subjects underwent a 2 h oral glucose tolerance test.Results: No significant differences in PCSK9 levels were found between healthy individuals and patients with CF, or between the groups with different degrees of glucose tolerance. No association was found between PCSK9 and markers of lipid metabolism; however, a positive correlation was found between PCSK9 and total insulin secretion and a negative one with insulin sensitivity in CF patients who had normal glucose tolerance. Conclusion:Circulating levels of PCSK9 in the CF population are comparable to those in the healthy population. There are no associations between PCSK9 levels and either glucose or lipid homeostasis parameters. Nevertheless, a statistically significant link was observed between PCSK9 and markers of insulin homeostasis, solely in CF patients who presented normal glucose tolerance. Further exploration of the relationship between PCSK9 and insulin homeostasis in CF patients with normal glucose tolerance is warranted.

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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%

“…1 CF patients with impaired glucose tolerance have reduced pancreatic ␤ cell number and a loss of insulin secretion. 2 The prevalence of glucose intolerance in CF patients has risen in recent decades, owing to increased longevity; older individuals are more likely to have glucose intolerance.…”

Section: Introductionmentioning

confidence: 99%

“…10 However, the impact of glucose intolerance on exercise capacity has not been determined. 1,3,6,[11][12][13][14][15] Female CF patients have worse lung function, earlier acquisition of chronic mucoid Pseudomonas aeruginosa, 16 and worse survival 17 than male CF patients. Sex is also known to influence pulmonary function in patients with CF-related diabetes.…”

Section: Introductionmentioning

confidence: 99%

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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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Increased glucose excursion in cystic fibrosis and its association with a worse clinical status

Abstract: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.

Cited by 69 publications

References 41 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

Proprotein Convertase Subtilisin/Kexin type 9 affects insulin but not lipid metabolism in cystic fibrosis

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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