Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

Mainguy, Catherine; Bellon, G.; Delaup, V.; Ginoux, Tiphanie; Kassai, Behrouz; Mazur, Stéphane; Rabilloud, Muriel; Remontet, Laurent; Reix, Philippe

doi:10.1515/jpem-2016-0184

Cited by 33 publications

(13 citation statements)

References 39 publications

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“…Longer-term outcome studies are currently underway. (96) may be more sensitive than OGTT to detect risk for progression to CFRD; however, evidence linking these results to long-term outcomes is lacking, and these tests are not recommended for screening (97). CFRD mortality has significantly decreased over time, and the gap in mortality between cystic fibrosis patients with and without diabetes has considerably narrowed (98).…”

Section: Future Considerationsmentioning

confidence: 99%

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2019

2018

Diabetes Care

2,290

987

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Background. Endothelial dysfunction, induced by some cardiovascular risk factors, is the early determinant of atherosclerotic cardiovascular disease. Moreover, it predicts incident type-2 diabetes that is associated with an increased risk of fatal and nonfatal cardiovascular events; however, no data demonstrating a possible interaction between them in predicting cardiovascular outcomes are available. Thus, we designed present study to evaluate the prognostic signi cance of the joint effect of endothelial dysfunction and new-onset type-2 diabetes in hypertensives. Methods. We enrolled 653 white never-treated hypertensive outpatients free of cardiovascular events from the CATanzaro Metabolic Risk factors (CATAMERI) study. All subjects were without type-2 diabetes, heart failure and chronic kidney disease. Endothelium-dependent vasodilation was investigated by intraarterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. Follow-up included periodic control visits every six months in our outpatients Clinic and ranged from 26-206 months (median 113). Patients were treated to reduce blood pressure <140/90 mmHg using standard lifestyle and pharmacological treatment. Incident type-2 diabetes and following cardiovascular events were monitored: fatal and nonfatal myocardial infarction and stroke, TIA, unstable angina, coronary revascularization procedures and symptomatic aortoiliac occlusive disease. Results. We documented 191 new cardiovascular morbid events (3.1%) at the cardiac (n=134), cerebrovascular (n=50), or peripheral (n=7) level. Dividing the study population in progressors and nonprogressors, progressors were older and had a higher baseline heart rate, fasting insulin, HOMA, creatinine, and hs-CRP mean values, while e-GFR and acetylcholine-stimulated forearm blood ow (FBF) were lower. Similarly, incident type-2 diabetes was higher in the progressors group. In the multiple Cox regression analysis, incident diabetes (HR=2.015, 95%CI=1.416-2.868), hs-CRP (HR=1.306, 95%CI=1.213-1.407) and acetylcholine-stimulated FBF (HR=0.729, 95%CI=0.633-0.839) maintained an independent association with the outcomes. The interaction between new-onset diabetes and FBF demonstrated that patients with new diabetes and maximal FBF under the median show a higher risk for subsequent cardiovascular events (HR=7.411, 95%CI=4.875-11.265). Conclusions. Endothelial dysfunction and new-onset diabetes predict cardiovascular events and their joint effect greatly increases this risk. These results highlight the importance of interaction between hemodynamic and metabolic alterations in predicting cardiovascular events.

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Section: Future Considerationsmentioning

confidence: 99%

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2019

2018

Diabetes Care

2,290

987

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“…The American Diabetes Association recommends testing CF patients from 10 years of age using the OGTT ( 97 ). The conventional OGTT, however, has been shown to have weak capacity to diagnose DM in CF individuals ( 98 ), as the inherent variability of the test and the variability observed in individual CF patients over time, means it does not accurately reflect glucose handling ( 99 ). The test itself is inconvenient and time consuming, thus adding to the patient’s already high burden of investigations, treatments, and hospital visits, causing low adherence to annual screenings ( 100 ).…”

Section: Diagnosis Of Cfrdmentioning

confidence: 99%

Cystic Fibrosis-Related Diabetes

2018

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Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD), which affects 40–50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR) also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

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“…Although OGTT is currently the recommended screening test for CFRD, it showed a great variability in CF patients with only 41% of the normal test confirmed in a subsequent test and a within‐subject coefficient of variation of 25% for 2‐h plasma glucose . Moreover, OGTT does not reflect glucose oscillation under real‐life conditions, and it seems to be less sensitive than continuous glucose monitoring . On the other hand, though LCI is a promising measure to monitoring early CF lung disease, its clinical utility remains to be defined …”

Section: Discussionmentioning

confidence: 99%

Ventilation inhomogeneity is associated with OGTT‐derived insulin secretory defects in cystic fibrosis

Colombo

Alicandro

Gambazza

et al. 2018

Pediatric Pulmonology

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Progressive deterioration of β-cell function is the main mechanism underlying diabetes in cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patients years before its onset. We aimed to evaluate if OGTT-derived indices of β-cell function are associated with early markers of lung disease. We carried out a cross-sectional study on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiple breath washout test. β-cell glucose sensitivity and the insulinogenic indices were used as markers of β-cell function and first-phase insulin response to glucose stimulus. We used sex-and age-adjusted multiple linear regression models to estimate the association between OGTT-derived indices and lung function measures. An increment of β-cell glucose sensitivity equal to its interquartile range was associated with an increase in ppFEV 1 of 7.6 points (95%CI: 0.8; 14.4) as well as with a decrease in LCI of −1.96 units (95%CI: −3.40; −0.51) and in S cond of −0.016 L −1 (95%CI: −0.026; −0.007).The corresponding figures for insulinogenic index were: 8.6 (95%CI: 3.4; 13.9) for ppFEV 1 , −2.03 (95%CI: −3.13; −0.94) for LCI, and −0.014 L −1 (95%CI: −0.021; −0.071) for S cond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with S cond . Deterioration of βcell function is related to early lung disease in young patients with mild to normal pulmonary function. This relationship is independent from hyperglycemia and mainly involves conductive airways.

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Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

Cited by 33 publications

References 39 publications

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2019

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2019

Cystic Fibrosis-Related Diabetes

Ventilation inhomogeneity is associated with OGTT‐derived insulin secretory defects in cystic fibrosis

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