Abnormal glucose tolerance and lung function in children with cystic fibrosis. Comparing oral glucose tolerance test and continuous glucose monitoring

BackgroundCystic fibrosis (CF) related diabetes (CFRD) is a common complication of CF. CFRD is associated with declining lung function even before its onset. Regular screening for CFRD using oral glucose tolerance test (OGTT) is recommended. Additionally, continuous glucose monitoring (CGM) has surfaced as a possible surveillance method, but evidence for its use and concordance with OGTT has not been established.MethodsChildren were prospectively recruited at CF center Lund to undergo both intermittent scan CGM (isCGM) and OGTT. Lung function was evaluated by spirometry and multiple breath washout. Demographic and clinical data were collected from the Swedish national CF registry.Results32 patients participated in the study, yielding 28 pairs of isCGMs and OGTTs. The OGTTs showed that two patients met the criteria of CFRD, seven had impaired glucose tolerance (IGT) and indeterminate glycemia (INDET) was found in eleven cases. The isCGM percent of measurements >8mmol/L and the number of peaks per day >11 mmol/L have correlations with intermediate OGTT glucose time points, but not the 2hour glucose value. Patients with abnormal glucose tolerance (AGT) had lower lung function than those with normal glucose tolerance demonstrated by both FEV1% predicted and lung clearance index (LCI).ConclusionCorrelations can be found between isCGM and OGTT in regards to the latter's intermediate time points. LCI demonstrates as well as FEV1% of predicted, worse lung function in children and adolescents with abnormal glucose tolerance in CF.     

Prevalence of hypoglycemia during oral glucose tolerance testing in adults with cystic fibrosis and risk of developing cystic fibrosis-related diabetes

Background

Hypoglycemia in cystic fibrosis (CF) patients during the oral glucose tolerance test (OGTT) has been reported; however, these patients have not been well-characterized. Few studies have examined whether hypoglycemia during the OGTT increases the risk of developing CF-related diabetes (CFRD). Objectives of this study were to describe the characteristics of CF patients with hypoglycemia during the OGTT and to determine the incidence and time to development of CFRD in those with hypoglycemia.

Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary exacerbation

BackgroundPatients with cystic fibrosis and normoglycemia (CF-NGT) have higher but still “normal” glucose levels in the Oral Glucose Tolerance Test (OGTT). Respiratory exacerbation is associated with metabolic stress. The objective of this study was to assess the glucose metabolism and its relation to the steady state pulmonary function (FEV1) in patients with CF-NGT, specifically during pulmonary exacerbations (PE).MethodsCF-NGT patients who were not on steroids, underwent OGTT and intravenous glucose tolerance tests (IVGTT) during PE and 4 weeks after complete recovery.ResultsOf the ten recruited patients two had diabetic OGTT and were excluded. The remaining normoglycemic patients displayed during PE a diabetic glucose tolerance with mean glucose levels of 233 ± 8 and 262 ± 11 mg/dl at 90 and 120 min respectively, compared with normal levels of 154 ± 21and 126 ± 20 mg/dl (p < 0.002) during the steady state. IVGTT showed a tendency to higher first phase insulin release during PE compared with the steady state.(min 3; 305 ± 80 vs. 216 ± 40 pmol\l p = 0.075). Finally, when relating the diabetic status to the general respiratory function we found a negative correlation between baseline FEV1 and glucose levels at 2 h after OGTT during PE (r = − 0.88, p = 0.002).ConclusionIn this pilot study we show that during PE patients with CF and normal glucose tolerance exhibited early latent diabetic glucose intolerance. As this hyperglycemia presents in the later parts of the OGTT it probably results from insufficient second phase insulin secretion during PE. The negative correlation observed here between the diabetic glucose tolerance and FEV1 indicate the need of interventional studies using insulin during PE in non-diabetic patients to determine its potential benefit on the outcome from recurrent PEs.     

Abnormal glucose tolerance and the 50-gram glucose challenge test in Cystic fibrosis

Diabetes has emerged as a major co-morbidity in cystic fibrosis (CF). The 75 g oral glucose tolerance test (OGTT) is used to screen for CF-related diabetes (CFRD) but is inconvenient, and adherence to screening is poor. The 50 g glucose challenge test (GCT) is shorter, performed non-fasting, and may serve to pre-screen the subset of individuals requiring confirmatory OGTT. We performed a pilot study in twenty-seven CF individuals across the glucose tolerance spectrum to test whether the GCT could identify subjects with abnormal glucose tolerance defined as 2-h OGTT glucose ≥7.8 mmol/L (2 h-AGT) or 1-h defined as 1-hr OGTT glucose ≥11.1 mmol/L (1 h-AGT). A GCT threshold of 8.1 mmol/L was 73% sensitive and 63% specific for 2hr-AGT and 80% sensitive and 65% specific for 1hr-AGT. Therefore, a screening GCT may reduce need for confirmatory OGTT for identifying AGT but a larger study is warranted to identify a robust cutoff for CFRD.     

Diagnosis of cystic fibrosis related diabetes: a selective approach in performing the oral glucose tolerance test based on a combination of clinical and biochemical criteria

BACKGROUND: Cystic fibrosis related diabetes (CFRD) has become increasingly common with the increasing longevity of patients with cystic fibrosis. The diagnosis of CFRD is important as its development may lead to a clinical deterioration which may be reversed with treatment. The oral glucose tolerance test (OGTT) is the method of choice in the diagnosis of CFRD, but performing OGTTs on all patients is inconvenient for patients and labour intensive for staff. The aim of this study was to identify a more selective approach in performing OGTTs in the diagnosis of CFRD based on the use of a combination of clinical and biochemical criteria. METHODS: Clinically stable adult patients with cystic fibrosis not known to be diabetic attending the Royal Brompton Hospital Cystic Fibrosis Clinic for their annual review were invited to return within a month to have an OGTT. The result of the OGTT was compared with the results of tests performed during the annual review. The sensitivities and specificities of various methods used in the screening or diagnosis of CFRD were determined using OGTT as the "gold standard" diagnostic method. The combination of clinical and biochemical criteria which resulted in the highest sensitivity and specificity in the diagnosis of CFRD was determined. RESULTS: Between August 1996 and May 1997 122 patients became eligible for the study, 91 of whom agreed to take part. The number of patients with normal, impaired, and diabetic glucose tolerance was 58 (64%), 21 (23%), and 12 (13%), respectively. When used alone, abnormal glycosylated haemoglobin (HbA1c) was found to have the highest sensitivity (83%; 95% CI 62 to 100) in the diagnosis of CFRD. The combination of an abnormal random blood glucose and/or abnormal HbA1c and/or symptoms of hyperglycaemia or weight loss was found to have the highest sensitivity (92%; 95% CI 76 to 100) in the diagnosis of CFRD. The specificity of this combination in the diagnosis of CFRD was 79% (95% CI 70 to 88). By selectively performing OGTTs in patients with one or more of the criteria cited above, 11 of the 12 patients with OGTT defined diabetes would have been identified. CONCLUSIONS: Patients with cystic fibrosis already have to undergo a large number of routine investigations. The selective approach in performing OGTTs described here has the potential to identify the majority of patients with CFRD without the need to perform this investigation on all patients. This approach is likely to be welcomed by patients and will lead to significant savings in terms of time and resources for patients and staff. Further larger studies are warranted to validate this selective approach in the diagnosis of CFRD.     

The association between body composition,leptin levels and glucose dysregulation in youth with cystic fibrosis

BackgroundOptimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls.MethodsIn a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, β-cell insulin secretion and fasting leptin levels were obtained.ResultsOf the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group.ConclusionsThis study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD.     

口服葡萄糖耐量试验和胰岛素释放试验在多囊卵巢综合征患者中的临床应用

目的探讨口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)在筛查多囊卵巢综合征(PCOS)患者糖代谢异常中的应用情况,并分析不同糖代谢状态下的PCOS患者糖、脂代谢特点。方法纳入符合鹿特丹标准、未经治疗的PCOS患者191例,测定身高、体重、基础生殖内分泌激素、血脂水平,并行OGTT和IRT检测,计算体重指数(BMI)、胰岛素抵抗稳态指数模型(HOMA-IR)、β细胞功能指数(HOMA-β)等参数。根据血糖水平将PCOS分成糖代谢正常(NGT)组、空腹血糖受损(IFG)组、糖耐量受损(IGT)组、以及2型糖尿病(T2DM)组,筛查各组的检出情况,并比较各组糖、脂代谢的差异。结果 PCOS患者糖代谢异常的发生率24.61%(47/191),其中IFG为3.66%,IGT为18.85%,T2DM为4.19%(其中4例为IFG合并IGT,重复纳入IFG组和IGT组);随着糖代谢紊乱加重,年龄、BMI有上升的趋势(P0.05)。血胰岛素高峰值出现在2h,滞后于血糖高峰值出现的1h。随着糖代谢的恶化,各时相的血糖及胰岛素水平逐渐升高,各组血脂紊乱也逐渐加剧(P0.05)。结论 PCOS患者糖代谢异常发生率较高,利用OGTT和IRT筛查PCOS患者糖代谢异常是十分必要和重要的。     

The effects of long-term therapy with oral hypoglycemic agents on the oral glucose tolerance test dynamics in male chemical diabetics.

The effect of fixed doses of oral hypoglycemic agents and placebo (diet alone) on the blood glucose, serum insulin, triglyceride, and cholesterol responses during oral glucose tolerance tests done annually for up to four years' follow-up was studied, in a double-blind manner, in five groups of mild male chemical diabetics. The drugs used were chlorpropamide (100 mg. O.D.), tolbutamide (500 mg. b.i.d.), phenformin (50 mg. O.D.), acetohexamide (250 mg. O.D.), and placebo. Each subject was given an individualized diet aimed at attaining and maintaining ideal weight. Comparison by chi-square analysis between the placebo group and each of the drug groups showed (a) no significant differences with regard to the number of subjects with normal glucose tolerance in each of the tests and (b) no change in the insulin secretion dynamics. Comparison between the initial test and each of the subsequent tests within each group showed (a) a greater number of subjects with normal glucose tolerance in the first follow-up test in the chlorpropamide group only, (b) no change in the insulin secretion dynamics except in the chlorpropamide group, where there was an increased insulin/glucose ratio in the first follow-up test, and (c) no change in the fasting serum triglyceride and cholesterol levels.     

Agreement and discrepancy in the evaluation of normal and diabetic oral glucose tolerance test.

Systematic analysis with a five-hour OGTT of 340 subjects representative of people likely to be examined in a center specialized in diabetes detection was performed by multiple discriminant analysis, which provides indices of discrimination for different sets of blood glucose (BG) values. The relative sensitivity and the relative specificity of six different diagnostic methods: Fajans and Conn, Wikerson, WHO, British Diabetic Association, UGDP, and European Study Group of Diabetes Epidemiology were computed, giving a quantitative determination for the degree of discrepancy in the definition of diabetes: only 48 per cent of the subjects are classified in the same way by any of the diagnostic criteria. The time(s) of sampling and the index or indices of OGTT which are the most efficient in screening diabetes were estimated from homogeneous groups of subjects universally recognized as nondiabetic (URND) or as diabetic (URD) according to the different diagnostic methods. Better discriminating power (DP) between URD and URND compared with the maximum DP as measured by D2 of Mahalanobis from the seven BG values of the OGTT is given by the two-hour (70.2 per cent) than by the one-hour (49.5 per cent) BG value when a single value is used; the one-two-hour BG value is the best set of two times (80.7 per cent). The different indices now in use for the classification of the OGTT have been found less effective than the weighted sum of one-two-hour BG values. The difficulty in obtaining highly specific diagnostic tests is discussed in relation to the consequences on a partly automated screening in large populations.     

Differences in the lower airway microbiota of infants with and without cystic fibrosis

BackgroundCystic fibrosis (CF) lung disease commences in infancy, and understanding the role of the microbiota in disease pathogenesis is critical. This study examined and compared the lower airway microbiota of infants with and without CF and its relationship to airway inflammation in the first months of life.MethodsInfants newly-diagnosed with CF were recruited into a single-centre study in Melbourne, Australia from 1992 to 2001. Bronchoalveolar lavage was performed at study entry. Healthy infants undergoing bronchoscopy to investigate chronic stridor acted as controls. Quantitative microbiological culture was performed and inflammatory markers were measured contemporaneously. 16S ribosomal RNA gene analysis was performed on stored samples.ResultsThirteen bronchoalveolar samples from infants with CF and nine from control infants, collected at median ages of 1.8-months (25th–75th percentile 1.5 to 3.1-months) and 5-months (25th–75th percentile 2.9 to 8.2-months) respectively, provided 16S rRNA gene data. Bacterial biomass was positively associated with inflammation. Alpha diversity was reduced in infants with CF and between-group compositional differences were apparent. These differences were driven by increased Staphylococcus and decreased Fusobacterium and were most apparent in symptomatic infants with CF.ConclusionIn CF lung disease, differences in lower airway microbial community composition and structure are established by age 6-months.