Glucose Tolerance in Patients with Cystic Fibrosis – Results from the German Cystic Fibrosis Registry

2020 ◽  
Vol 232 (04) ◽  
pp. 210-216
Author(s):  
Nicole Prinz ◽  
Julia Wosniok ◽  
Doris Staab ◽  
Manfred Ballmann ◽  
Christian Dopfer ◽  
...  

Abstract Background Oral glucose tolerance (OGT) deteriorates progressively in cystic fibrosis (CF). Clinical registries provide a unique basis to study real-world data. Patients & methods OGT tests (OGTTs) documented in the German CF-registry in 2016 were classified according WHO, modified by ADA: normal glucose tolerance (NGT), indeterminate glycaemia (INDET), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, diabetes mellitus (DM). To study the association with lung function, multivariable regression adjusted for age, sex, and CFTR mutation was performed. Results Overall, OGTT screening was done in 35% of CF patients ≧10 years. Of the 996 patients (46.4% females; median age (IQR): 19 (14–27) years) with evaluable OGTTs, 56.2% had either NGT or INDET, whereas 34% had a pre-diabetic OGTT (IFG; IGT; IFG+IGT) and 9.8% a diabetic OGTT. 7 patients had glucose tolerance abnormalities <10 years. DM was more common in females or patients with F508del homozygote mutation, whereas IFG was more frequent in males (all p<0.05). Nearly 75% of patients after transplantation and about half with enteral/parental nutrition and/or steroid use had either a pre-diabetic or diabetic glucose tolerance. In the adjusted model, age (p<0.001) and OGTT category (p=0.013) had both a significant impact on %FEV1. Conclusion Our data of the German CF-registry highlights incidence of glucose tolerance abnormalities in second decade of life in CF patients. However, it also underlines the need for improvement of the documentation and/or performance of OGTT screening in real-world CF care.

2017 ◽  
Vol 40 (2) ◽  
pp. 59 ◽  
Author(s):  
Adèle Coriati ◽  
Elizabeth Arslanian ◽  
Guillaume F Bouvet ◽  
Annik Prat ◽  
Nabil G Seidah ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250036
Author(s):  
Amy Darukhanavala ◽  
Filia Van Dessel ◽  
Jannifer Ho ◽  
Megan Hansen ◽  
Ted Kremer ◽  
...  

Background Cystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%–50% of people with CF eventually develop CF–related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states. Objective To determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs. Methods This retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states. Results Mean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250). Conclusion There is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.


1985 ◽  
Vol 68 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Richard T. Moxley ◽  
William Kingston ◽  
Robert C. Griggs

1. The concentration of amino acids in whole blood was measured before and during standard 5 h oral glucose tolerance testing in six male patients with myotonic dystrophy and five normal males. The plasma levels of insulin and glucose were also determined. 2. From 90 to 240 min after glucose ingestion there was a striking decline in venous alanine concentration in the patients with myotonic dystrophy in contrast to a slight rise in alanine in the normal group. 3. The patients displayed normal glucose tolerance, and there was a sustained fall in the venous concentration of the insulin-sensitive amino acids comparable with that seen in the normal controls. However, the patients showed a threefold increase of plasma insulin after glucose. 4. These data indicate an abnormal regulation of alanine in myotonic dystrophy which may be the result of an alteration in muscle synthesis of this amino acid. This defect in alanine synthesis may be due to a decreased availability of intracellular pyruvate caused by the insulin resistance that exists in these patients.


2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Chelsea Lawson ◽  
S Naseeruddin Ahmed ◽  
Cassandra Brady ◽  
Ashley H Shoemaker

Abstract Background Type 2 diabetes (T2D) in youth is increasing in prevalence. Diabetes screening is recommended for at-risk youth but best-practice strategies for management of pediatric prediabetes are unknown. This study leverages a pediatric prediabetes clinic to assess identification of high-risk patients, the rate of clinic follow-up and progression to T2D in youth over time. Methods Retrospective chart review of children referred to a single center for evaluation of prediabetes over a 3-year period. Measurements included hemoglobin A1c (HbA1C) and oral glucose tolerance testing. Patients were classified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or T2D based on 2019 American Diabetes Association criteria. Patients classified as IGT/T2D were prescribed metformin. Results Of the 254 patients included; 25.6% had IGT and 6.7% had T2D. The IGT/T2D groups were older and more obese than the NGT group. There was a moderate correlation between HbA1C and fasting glucose (r = 0.59, P &lt; 0.001); HbA1C and 2-hour glucose (r = 0.63, P &lt; 0.001). Over the 3-year study, 52 of 82 patients with IGT/T2D (63%) returned for follow-up. Four patients regained NGT; 3 of those had isolated impaired fasting glucose (100 to 102 mg/dL). Three patients (4.6%) progressed from IGT to T2D over an average of 13 ± 6.2 months. In those patients, body mass index had increased 1.7 ± 2.3 kg/m2 from baseline. Conclusions A pediatric prediabetes clinic may allow for identification of high-risk youth but lost to follow-up rates are high. Continued weight gain is a risk factor for progression to T2D and effective weight management programs are needed.


1983 ◽  
Vol 55 (2) ◽  
pp. 512-517 ◽  
Author(s):  
G. W. Heath ◽  
J. R. Gavin ◽  
J. M. Hinderliter ◽  
J. M. Hagberg ◽  
S. A. Bloomfield ◽  
...  

Physically trained individuals have a markedly blunted insulin response to a glucose load and yet have normal glucose tolerance. This phenomenon has generally been ascribed to long-term adaptations to training which correlate with maximal oxygen uptake (VO2max) and reduced adiposity. Our study was undertaken to test the hypothesis that residual effects of the last bouts of exercise play an important role in this phenomenon. Eight well-trained subjects stopped training for 10 days. There were no significant changes in VO2max (58.6 +/- 2.2 vs. 57.6 +/- 2.1 ml/kg), estimated percent body fat (12.5 +/- 0.7 vs. 12.5 +/- 0.8%), or body weight. The maximum rise in plasma insulin concentration in response to a 100-g oral glucose load was 100% higher after 10 days without exercise than when the subjects were exercising regularly. Despite the increased insulin levels, blood glucose concentrations were higher after 10 days without exercise. Insulin binding to monocytes also decreased with physical inactivity. One bout of exercise after 11 days without exercise returned insulin binding and the insulin and glucose responses to an oral 100-g glucose load almost to the initial “trained” value. These results support our hypothesis.


2014 ◽  
Vol 106 (2) ◽  
pp. e25-e29 ◽  
Author(s):  
Toshihiro Matsuo ◽  
Yoshiki Kusunoki ◽  
Tomoyuki Katsuno ◽  
Takashi Ikawa ◽  
Takafumi Akagami ◽  
...  

Author(s):  
Eiichiro Satake ◽  
Rie Matsushita ◽  
Kazuteru Kitsuda ◽  
Kohnosuke Ohtaka ◽  
Eiko Nagata ◽  
...  

AbstractUrinaryIn Study 1 (328 schoolchildren), fasting and postprandial UMI were measured, with ΔUMI defined as the difference between fasting and postprandial UMI levels. In Study 2, oral glucose tolerance tests and UMI measurements were conducted in 18 children with suspected having diabetes.For Study 1, ΔUMI was observed [−0.65 (−3.9, 1.35) mg/g creatinine]. For Study 2, children with diabetes or impaired glucose tolerance had a significantly higher ΔUMI than children with normal glucose tolerance.These studies demonstrated the normal range of UMI in children and possibility of a novel biomarker for early detection of glucose intolerance in children.


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