Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary exacerbation (original) (raw)
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European Journal of Endocrinology, 2005
Objective: To evaluate insulin-secretion kinetics and insulin sensitivity in cystic fibrosis (CF) patients with normal glucose tolerance (CF-NGT), impaired glucose tolerance (CF-IGT) or CF-related diabetes (CFRD), and the potential effects of moderate hyperglycemia on clinical and nutritional status. Design and methods: Cross-sectional study including 50 outpatients with CF. Patients underwent both oral (OGGT) and intravenous (IVGTT) glucose tolerance tests in order to assess insulin secretion and peripheral insulin sensitivity. Homeostasis assessment model and OGGT were used to investigate insulin sensitivity. Forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) were measured to evaluate pulmonary function. Body mass index (BMI) was determined to assess nutritional status. Results: Insulin secretion was significantly decreased (and delayed at OGTT) in the CFRD group (n ¼ 9) versus the CF-IGT group (n ¼ 10) and the CF-IGT versus the CF-NGT group (n ¼ 31). Insulin sensitivity was significantly different in the CF-IGT and CFRD groups versus the CF-NGT group. FEV 1 , FVC and BMI presented a significant linear correlation with plasma glucose value at 120 min at OGTT and were significantly lower in both CF-IGT and CFRD versus the CF-NGT group, whereas no differences were found between the CF-IGT and CFRD groups. Conclusions: CF patients with IGT present diminished insulin secretion and increased peripheral insulin resistance, correlating with a worse clinical status, undernutrition and impaired pulmonary function. These findings open the question of whether early treatment of mild alterations of glucose metabolism with insulin secretagogues or short-action insulin may lead to improvement of clinical status in CF patients.
Scoping review: relationship between glucose tolerance and pulmonary decline in cystic fibrosis
Academia Medicine, 2024
Cystic fibrosis-related diabetes (CFRD) causes deterioration of cystic fibrosis (CF) lung disease, thereby increasing mortality. Lung function decline occurs at glycemic levels below current CFRD diagnostic thresholds. CFRD may be better defined by examining the relationship between lung function decline and elevated glucose levels in individuals without diabetes. This scoping review examines the existing literature on the relationship between oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) values, and percent predicted forced expiratory volume in one second (%FEV1) and forced vital capacity (FVC) to determine whether alternative glucose levels would be more appropriate for defining CFRD based on lung function decline. Electronic database searches were performed on Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials in June 2023. Studies that assessed glucose levels from glucose tolerance test (GTT) and/or CGM and their relationship to %FEV1 and FVC were included. A total of 10 studies were included. For OGTT, three studies found that one-hour OGTT plasma glucose levels > 11.0 mmol/L were inversely associated with %FEV1. Two studies found that peak GTT levels were inversely associated with %FEV1. For CGM, four studies found inverse associations between %FEV1 and percent predicted forced vital capacity (%FVC) and the number of glucose measurements ≥ 11.0 mmol/L, the percentage of time spent with glucose > 7.8 mmol/L, or the area under the curve > 7.8 mmol/L. Intermediate OGTT values and CGM metrics are associated with lung function decline in CF without diabetes. Correlations between CGM and OGTT values need to be established. Prospective studies are required to determine whether treating elevated intermediate OGTT values can prevent lung function decline before revising CFRDdiagnostic criteria.
Clinical Nutrition, 2012
Background & aims: Impaired growth and nutritional status in CF may be related to progressive insulin deficiency before CF-Related Diabetes has established. Aim of this study was to analyse the association of circulating insulin with nutritional status and lung function in CF patients with normal glucose tolerance (NGT). Methods: We performed OGTT in 152 consecutive CF patients aged 8e20 years: 115 of them had NGT and were included in the study. Areas under the curves (AUC) of glucose, insulin and c-peptide after 120 min were calculated. Quartiles (Q) of increasing fasting insulin (fINS-Q) and c-peptide (fCP-Q) levels were calculated in CF patients. Respiratory function parameters (FEV1, FVC), Standard Deviation Scores (SDS) of height, weight and BMI were compared between Q1 and the three higher Q. Multiple regression analysis was used to analyse the association of fasting insulin, c-peptide or OGTT derived indices with nutritional or respiratory parameters. Results: Compared to patients in fINS-Q4 or fCP-Q4, those in fINS-Q1 or in fCP-Q1 respectively showed lower levels of insulin AUC or c-peptide AUC (both P < 0.0001), weight-SDS (P ¼ 0.013, P ¼ 0.007), BMI-SDS (P ¼ 0.010, P ¼ 0.002), FEV1 (P ¼ 0.076, P ¼ 0.013) and FVC (P ¼ 0.101, P ¼ 0.009). Age-and genderadjusted regression analysis showed significant associations of fINS and fCP with SDS of BMI (P ¼ 0.023 and P ¼ 0.001 respectively), fCP was significant associated with FEV1 (P ¼ 0.01). AUC insulin/AUC glucose ratio (P < 0.0001) and AUC c-peptide/AUC glucose ratio (P ¼ 0.0001) were significantly associated with FEV1. Conclusions: Insulin deficiency in CF patients with NGT has a significant impact on clinical outcomes.
Increased glucose excursion in cystic fibrosis and its association with a worse clinical status
Journal of Cystic Fibrosis, 2007
Background: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. Methods: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. Results: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV 1 ). Conclusion: 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.
Glucose Tolerance during Pulmonary Exacerbations in Children with Cystic Fibrosis
PLoS ONE, 2012
Background: Patients with Cystic Fibrosis (CF) are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. Methods: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. Results: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77). At the follow up OGTT, 8 of 9 (89%) remained within their respective glucose tolerance status groupings. Conclusion: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.
Journal of Pediatric Endocrinology and Metabolism, 1994
The aim of our study was to determine whether first-phase insulin response to intravenous (i.v.) glucose could be used as a simple and rapid test to identify cystic fibrosis (CF) patients at risk to develop diabetes mellitus. Forty consecutive CF patients with normal fasting blood glucose values but with different degrees of glucose tolerance on the standard oral glucose tolerance test (22 with normal glucose tolerance, 16 with impaired glucose tolerance, 2 with diabetes mellitus) and 12 normal subjects, matched for age and body mass index, underwent an i.v. glucose bolus to evaluate early phase insulin release. When compared to the normal subjects, CF patients had significantly reduced basal (76 ± 50 vs 108 ± 30 pM/1, 2p<0.02) and glucose stimulated insulin levels (1+3 min insulin=456 ± 275 vs 951 ± 170 pM/1, 2p<0.01). Early phase insulin release, however, did not differentiate between CF patients with normal and impaired glucose tolerance; also in the two diabetic patients insulin levels did not clearly differ from those observed in the other groups of CF subjects. In conclusion, first-phase insulin response may identify an impairment of B-cell function in CF subjects; however, it does not discriminate between different degrees of glucose tolerance, as determined by the oral glucose tolerance test and, therefore, it does not reliably identify those patients who will eventually develop overt diabetes mellitus.
The Journal of Pediatrics, 2010
Objective To determine prospectively the long-term natural history of glucose homeostasis in adult patients with cystic fibrosis (CF). Study design Between 1996 and 2005, a total of 971 modified oral glucose tolerance tests (OGTTs) were performed in 329 patients with CF without recognized CF-related diabetes (CFRD). Patients were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), CFRD without fasting hyperglycemia (FH), or CFRD with FH. Data were collected at baseline from the Toronto Cystic Fibrosis database.
Impaired Fasting Glucose in Cystic Fibrosis
Diabetes Care, 2010
OBJECTIVE -While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.
Acta Paediatrica, 2001
In patients with cystic brosis (CF), glucose intolerance preceding diabetes (prediabetes) may have adverse effects on nutritional status and respiratory function, which are reversible after the start of insulin therapy. Respiratory function (forced vital capacity and forced expiratory volume in one second) and body mass index (BMI) were compared retrospectively in a French cohort of 14 patients during the 5 y preceding insulin therapy for diabetes and in 14 age-and sex-matched controls with normal oral glucose tolerance tests. In the diabetic group, all three parameters deviated increasingly from the values in the controls; the differences became statistically different during the 6 mo before insulin therapy. The effect was more important in patients for whom diabetes mellitus was diagnosed on the basis of symptoms of hyperglycaemia than in patients for whom it was diagnosed by systematic screening, but still present in the latter. After insulin was started, respiratory function improved and the BMI returned to normal within 1 y. The annual insulin requirement increased from 0.62 during the rst year to 1.25 during the fth year. Glycosylated haemoglobin (HbA Ic) values ranged from 6.6 to 7.8%. Only 2 episodes of severe hypoglycaemia were recorded over 42 patient-years of follow-up. The insulin regimen most often used was two daily injections of a mixture of short-and intermediate-acting insulin (n = 10) given with an insulin pen. Conclusion: The clinical status of CF patients who will need insulin therapy deteriorates before the start of insulin. In patients with CF-related diabetes, with or without fasting hyperglycaemia, insulin therapy improves anabolism and provides good glycaemic control with few severe hypoglycaemic episodes.