|Year : 2020 | Volume
| Issue : 2 | Page : 86-89
Use of continuous glucose monitoring in diagnosis and management of cystic fibrosis-related diabetes in children
Sze M Ng, Akinsola Ogundiya
Department of Paediatrics, Southport and Ormskirk Hospital NHS Trust, Ormskirk, United Kingdom
|Date of Submission||18-Apr-2019|
|Date of Decision||25-Jun-2019|
|Date of Acceptance||22-Aug-2020|
|Date of Web Publication||24-Jun-2020|
Dr. Sze M Ng
Consultant Paediatric Endocrinologist Southport and Ormskirk NHS Trust.
Source of Support: None, Conflict of Interest: None
Background: Cystic fibrosis related diabetes (CFRD) is the most common comorbidity in children with cystic fibrosis (CF). Routine screening for CFRD is the oral glucose tolerance test (OGTT) where blood glucose levels are measured at 0 and 120 min. Studies have found that patients with CFRD often have an initial postprandial raised blood glucose level at 60 min while still achieving a normal 120-min blood glucose level from an OGTT, resulting in delayed diagnosis and treatment of CFRD. The aim of this study was to assess whether the use of continuous glucose monitoring (CGM) could aid in early diagnosis and treatment in children with CFRD. Methods: We included five patients diagnosed with CFRD. All the patients had a raised 1-h OGTT blood glucose level (>11.0 mmol/L), and consented for CGM for two weeks. Treatment was commenced initially as bolus fast-acting insulin (Novorapid), which targeted the initial postprandial rise in blood glucose level. If the CGM showed continued overnight hyperglycemia, basal long-acting insulin (Lantus) was later added to the treatment regimen. Results: All the patients showed improvement in their forced expiratory volume at 1s and weights following insulin treatment. Conclusions: Abnormalities of glucose metabolism have an adverse impact on morbidity and mortality in patients with CF. Early detection of glucose abnormalities using CGM and early targeted intervention is an important factor to consider in improving lung function and nutritional status. Further studies are warranted on the use of CGM in the early detection and management of CFRD in children.
Keywords: Children, continuous glucose monitoring, cystic fibrosis-related diabetes
|How to cite this article:|
Ng SM, Ogundiya A. Use of continuous glucose monitoring in diagnosis and management of cystic fibrosis-related diabetes in children. J Diabetol 2020;11:86-9
| Introduction|| |
Cystic fibrosis-related diabetes (CFRD) affects approximately 2% of children with cystic fibrosis (CF), and approximately 35% of patients will develop it by adulthood. With increased survival in patients with CF, the incidence of CFRD has been increasing. CFRD is a recognized factor for severe pulmonary disease and mortality in patients with CF.,, The International Society for Pediatric and Adolescent Diabetes in 2018 describes it as the most common comorbidity in CF. CFRD can be clinically silent, and several guidelines including the European Cystic Fibrosis Society and the American Diabetes Association advocate routine screening from the age of 10 years., Routine screening for CFRD is the oral glucose tolerance test (OGTT) in which a 75-g glucose load is given and blood glucose levels are measured in intervals at 0 and 120 min. United Kingdom (UK) surveys have found variation in screening processes for CFRD, from the age of screening to the methods of screening and criterion for diagnosis of CFRD.,
The World Health Organization recommends the OGTT as a diagnostic tool for CFRD based on blood glucose levels at 0 and 120 min, using the 120-min blood glucose reading as the gold standard for the diagnosis of CFRD., However, respiratory deterioration due to hyperglycemia may often occur before patients fulfil that criterion using the 120-min OGTT criterion. Studies have found that many patients with CFRD have initial postprandial raised blood glucose levels at 60 min while still achieving a normal 120-min blood glucose from an OGTT. Therefore, relying on the 120-min OGTT threshold may often miss those who have had a transiently large rise in postprandial blood glucose levels at 60 min. Hyperglycemia has adverse effects on the lung and can exacerbate weight loss, therefore early diagnosis and treatment is important to reduce morbidity and mortality in patients with CF. The aim of this study was to assess whether the use of continuous glucose monitoring (CGM) could aid in early diagnosis and treatment in children with CFRD.
| Materials and Methods|| |
We audited the case notes of all new CFRD diagnoses at the Southport and Ormskirk Hospital NHS Trust, UK, between January 2017 and June 2018, as the new department protocol for screening CFRD was to record OGTT at 0, 1, and 2h from 2017 from 10 years of age. Patients with abnormal 1-h OGTT then consented to wear a CGM device, Dexcom G6, (Dexcom, San Diego, California, United States) for two weeks. The blood glucose downloads were reviewed weekly by the diabetes team and the pediatric endocrinologist. All patients continued wearing the CGM once they were started on treatment for a further month due to the risk of hypoglycemic episodes and until blood glucose and insulin dosing were stable. Frequent reviews were undertaken monthly, which included blood glucose download from the CGM, spirometry, weight, and general well-being.
| Results|| |
We included five patients diagnosed with CFRD (five females, zero male) who were under follow-up care of the specialist CF team. Four patients with CF, who were older than 10 years, underwent routine annual OGTT, whereas a 6-year-old patient was noted to have a high blood glucose level (>11.0 mmol/L) on random testing during a ward admission and an OGTT was subsequently arranged. All five patients had a raised 1-h OGTT blood glucose level and they consented for CGM for two weeks. The CGM showed that blood glucose levels were persistently above 11.0 mmol/L and assisted in the diagnosis of CFRD.
All the patients who had been on routine steroids were off steroids at the diagnosis of CFRD. Treatment was commenced initially as bolus fast-acting insulin NovoRapid® (Novo Nordisk, Bagsværd, Denmark), which targeted the initial postprandial rise in blood glucose level. If the CGM showed continued overnight hyperglycemia, basal long-acting insulin Lantus® (sanofi-aventis, Paris, France) was later added to the treatment regimen. In three patients, sustained postprandial glucose abnormalities were detected, and they required only bolus insulin with meals. Two patients showed frequent elevated overnight, fasting, and postprandial glucose levels, and they were commenced on multiple daily insulin regimen. CGM data guided the decision to start insulin and the choice of insulin regimen and insulin dosing. All the patients continued with their routine care with the CF and diabetes teams for frequent monitoring. Summary of demographics and treatment regimen is shown in [Table 1]. CGM average glucose profiles are shown as examples for patient case 1 and 2 in [Figure 1]. Three patients showed improvement of 7%–12% in their forced expiratory volume at 1s (FEV1). All the patients showed weight gain improvement at six months between 0.8% and 6.0% from the diagnosis of CFRD. No patients had severe or recurrent hypoglycemia in the three months following initiation of insulin treatment. All the patients showed improvements in glycosylated hemoglobin (HbA1c) in six months of starting insulin therapy but did not reach statistical significance.,
|Figure 1: Continuous glucose monitoring average glucose profiles of patient case 1 and 2 before and after treatment|
Click here to view
| Discussion|| |
There is currently no uniformity to screening methods for CFRD in children. The OGTT has been the routine diagnostic test, and up to 10% of adult patients with CF develop a raised blood glucose level (>11.0 mmol/L) at 60-min during OGTT screening., Studies have reported that up to 20% of children with CF present with high blood glucose level (>11.0 mmol/L) at the 60-min OGTT are at high risk of CFRD. There is a reported female preponderence in incidence of CFRD and it is associated with duration of CF.,[ 18]
Studies have reported the use of CGM in assessing patients with CF for CFRD to evaluate postprandial and overnight hyperglycemia that may be masked using conventional screening.,, Compared to the OGTT alone, CGM increased pickup rates of CFRD from 11.9% to approximately 50% in a pediatric population. In our cohort, CGM played a role not only in early diagnosis of CFRD but in assisting the decisions to commence insulin therapy. Although we currently use the OGTT as a screening tool, there is scope to extend CGM as a part of a routine diagnostic tool for CFRD in children. The limitations of using CGM may include the cost and the mild discomfort of a wearable technology for some children.
HbA1c is not a recommended screening tool for CFRD as it is unreliable and has been reported to underestimate the presence of CFRD in 70% of patients diagnosed by the OGTT. In this cohort, HbA1c improved within six months of insulin treatment but this did not reach statistical significance.
Insulin is the recommended treatment for CFRD and international guidelines such as the American and the European Cystic Fibrosis society advocate early intervention., Studies have reported on deterioration of pulmonary function tests, weight, and other clinical parameters before detection of hyperglycemia and CFRD,, whereas early insulin therapy improves lung function and nutritional status even in the absence of fasting hyperglycemia. The exact mechanisms for lung function improvements are unclear. It may be hypothesized that glycemic status resulted in better protective immunity, therefore lowering the chances of pathogenic lung infections such as Staphylococcus and Pseudomonas infections, resulting in better lung function.
Hypoglycemia remains a significant risk for insulin therapy in patients with CFRD, and families must be taught about the management of hypoglycemia. All our five patients were carefully monitored using CGM and regularly reviewed by the diabetes team. We commenced our patients on rapid-acting insulin Novorapid with meals initially to deal with postprandial blood glucose rises and later added basal long-acting insulin (Lantus) for patients with fasting or overnight hyperglycemia. All the patients showed improvement in weight and FEV1 in concordance with reported studies., Bizzarri et al. showed improvement in body mass indices, and several other studies have reported improvements in nutritional status and lung function on starting insulin treatment.,, It is possible that weight gain may have been improved in general because of insulin therapy.
A limitation of this case series study was the small number of patients reviewed, and each case was unique, which did not allow overall statistical comparisons. Further large-scale randomized studies with adequate sample sizes would be warranted in the future.
| Conclusion|| |
Early insulin therapy in CFRD improves weight and pulmonary function in children with CF. CGM should become an integral part of assessment of patients of CF with abnormal OGTT results. Our study shows that early detection of glucose abnormalities using CGM and early targeted insulin treatment improve lung function and nutritional status. Further large studies are warranted on the use of CGM in the early detection and management of CFRD in children.
We thank the pediatric CF team and diabetes team for collating audit data during this period.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Whitehouse J AA, Haworth C. The prevalence of cystic fibrosis-related diabetes in a large screened adult CF population. Pediatr Pulmonol 2007;42:395-6.
Brennan AL, Geddes DM, Gyi KM, Baker EH. Clinical importance of cystic fibrosis-related diabetes. J Cystic Fibrosis 2004;3:209-22.
Jones GC, Sainsbury CAR. A practical approach to glucose abnormalities in cystic fibrosis. Diabetes Ther 2016;7:611-20.
Terliesner N, Vogel M, Steighardt A, Gausche R, Henn C, Hentschel J, et al
. Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function. J Pediatr Endocrinol Metab 2017;30:815-21.
Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ. Epidemiology of cystic fibrosis-related diabetes. J Pediatr 2005;146:681-7.
Moran A, Pillay K, Becker D, Granados A, Hameed S, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: Management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes 2018;19:64-74.
Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, et al
.; European Cystic Fibrosis Society. European cystic fibrosis society standards of care: Best practice guidelines. J Cystic Fibrosis 2014;13:S23-42.
Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, et al
. Clinical care guidelines for cystic fibrosis—Related diabetes. Diabetes Care 2010;33:2697-708.
Wickens-Mitchell KL, Gilchrist FJ, McKenna D, Raffeeq P, Lenney W. The screening and diagnosis of cystic fibrosis-related diabetes in the United Kingdom. J Cystic Fibrosis 2014;13:589-92.
Mohan K, Miller H, Burhan H, Ledson MJ, Walshaw MJ. Management of cystic fibrosis related diabetes: A survey of UK cystic fibrosis centers. Pediatr Pulmonol 2008;43:642-7.
World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF consultation. Geneva, Switzerland: WHO;2006. p. 1-50.
Waugh N, Royle P, Craigie I, Ho V, Pandit L, Ewings P, et al
. Screening for cystic fibrosis-related diabetes: A systematic review. In:NIHR Health Technology Assessment Programme: Executive Summaries. Southampton, UK: NIHR Journals Library; 2012.
Rosenecker J, Höfler R, Steinkamp G, Eichler I, Smaczny C, Ballmann M, et al
. Diabetes mellitus in patients with cystic fibrosis: The impact of diabetes mellitus on pulmonary function and clinical outcome. Eur J Med Res 2001;6:345-50.
Waugh N, Royle P, Craigie I, Ho V, Pandit L, Ewings P, et al
. Screening for cystic fibrosis-related diabetes: A systematic review. Health Technol Assess 2012;16:iii-iv, 1-179.
Brodsky J, Dougherty S, Makani R, Rubenstein RC, Kelly A. Elevation of 1-hour plasma glucose during oral glucose tolerance testing is associated with worse pulmonary function in cystic fibrosis. Diabetes Care 2011;34:292-5.
Ode KL, Frohnert B, Laguna T, Phillips J, Holme B, Regelmann W, et al
. Oral glucose tolerance testing in children with cystic fibrosis. Pediatr Diabetes 2010;11:487-92.
Moran A, Doherty L, Fau-Wang X, Thomas W. Abnormal glucose metabolism in cystic fibrosis. J Pediatr 1998;133:10-17.
Franzese A, Valerio G, Buono P, Spagnuolo MI, Sepe A, Mozzillo E, et al
. Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis. J Pediatr Endocrinol Metab 2008;21:109-16.
Leclercq A, Gauthier B, Rosner V, Weiss L, Moreau F, Constantinescu AA, et al
. Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients. J Cystic Fibrosis 2014;13:478-84.
Khammar A, Stremler N, Dubus JC, Gross G, Sarles J, Reynaud R. [Value of continuous glucose monitoring in screening for diabetes in cystic fibrosis]. Arch Pediatr 2009;16:1540-6.
Jefferies C, Solomon M, Perlman K, Sweezey N, Daneman D. Continuous glucose monitoring in adolescents with cystic fibrosis. J Pediatr 2005;147:396-8.
Lanng S, Hansen A, Thorsteinsson B, Nerup J, Koch C. Glucose tolerance in patients with cystic fibrosis: Five year prospective study. BMJ 1995;311:655-9.
Lanng S, Thorsteinsson B, Nerup J, Koch C. Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. Eur J Pediatr 1992;151:684-7.
Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Resp Crit Care Med 2000;162:891-5.
Moran A, Pekow P, Grover P, Zorn M, Slovis B, Pilewski J, et al
.; Cystic Fibrosis Related Diabetes Therapy Study Group. Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: Results of the cystic fibrosis related diabetes therapy trial. Diabetes Care 2009;32:1783-8.
Rolon MA, Benali K, Munck A, Navarro J, Clement A, Tubiana-Rufi N, et al
. Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and effects of insulin therapy. Acta Paediatr 2001;90:860-7.
Bizzarri C, Lucidi V, Ciampalini P, Bella S, Russo B, Cappa M. Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance. J Endocrinol Invest 2006;29:RC1-4.
Dobson L, Hattersley AT, Tiley S, Elworthy S, Oades PJ, Sheldon CD. Clinical improvement in cystic fibrosis with early insulin treatment. Arch Dis Child 2002;87:430-1.
Nousia-Arvanitakis S, Galli-Tsinopoulou A, Karamouzis M. Insulin improves clinical status of patients with cystic-fibrosis-related diabetes mellitus. Acta Paediatr 2001;90:515-9.
Hameed S, Morton JR, Field PI, Belessis Y, Yoong T, Katz T, et al
. Once daily insulin detemir in cystic fibrosis with insulin deficiency. Arch Dis Child 2012;97:464-7.