Highlights
- •No randomised studies evaluating continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in the management of cystic fibrosis related diabetes (CFRD) exist.
- •In our systematic review and meta-analysis, we found the weighted mean difference in plasma HbA1c was 4.1 mmol/mol (0.4%) lower in CGM group compared to SMBG group over >6 weeks of follow-up.
- •Studies included in our meta-analysis demonstrated moderate-to-high risk of bias. Publication bias was also present.
- •Effects of CGM on pulmonary, non-pulmonary and psychosocial outcomes were lacking.
Abstract
Background
Treatment of cystic fibrosis related diabetes (CFRD) can improve outcomes and use
of continuous glucose monitoring (CGM) can positively impact glycemic control. We
conducted a systematic review to assess current evidence on CGM compared to self-monitoring
of blood glucose (SMBG) in the management of CFRD to determine its effect on glycemic,
pulmonary, non-pulmonary and quality of life outcomes.
Methods
Using pre-defined selection criteria, we searched MEDLINE, Embase, CENTRAL, Evidence-Based
Medicine Reviews, grey literature and six relevant journals for studies using CGM
and/or SMBG in CFRD with greater than 6 weeks of follow-up and reported change in
HbA1c. The primary outcome was weighted mean difference (WMD) in plasma HbA1c between
CGM and SMBG groups. Secondary outcomes included exploring interrelationships between
CGM metrics and effects on disease-specific pulmonary, non-pulmonary and quality of
life outcomes.
Results
A total of 1671 references were retrieved, 862 studies screened and 124 full-texts
assessed for eligibility. No studies directly compared CGM to SMBG. A meta-analysis
of seventeen studies of 416 individuals (CGM = 138, SMBG = 278) found CGM group had
4.1 mmol/mol (95% CI -7.9 to -0.30, p = 0.034) lower HbA1c compared to SMBG group. Most studies demonstrated moderate-to-high
risk of bias. Publication bias was also present. Heterogeneity was high and meta-regression
identified duration of follow-up in SMBG group as main contributor.
Conclusion
Our findings suggest use of CGM may be associated with improved glycemic control compared
to SMBG in CFRD, however evidence of benefit on pulmonary, non-pulmonary and psychosocial
outcomes are lacking.
Keywords
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References
- Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the cystic fibrosis foundation patient registry.Ann Intern Med. 2014; 161: 233-241
- Cystic fibrosis birth rates in Canada: a decreasing trend since the onset of genetic testing.J Pediatr. 2005; 147: 312-315
- Diabetes mellitus associated with cystic fibrosis.J Pediatr. 1988; 112: 373-377
- Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex.Am J Respir Crit Care Med. 2015; 191: 194-200
- Diabetes mellitus in patients with cystic fibrosis: the impact of diabetes mellitus on pulmonary function and clinical outcome.Eur J Med Res. 2001; 6: 345-350
- Cystic Fibrosis–related diabetes: current trends in prevalence, incidence, and mortality.Diabetes Care. 2009; 32: 1626
- Presence of cystic fibrosis-related diabetes mellitus is tightly linked to poor lung function in patients with cystic fibrosis: data from the European epidemiologic registry of cystic fibrosis.Pediatr Pulmonol. 2001; 32: 343-350
- Staphylococcus aureus and pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes.Eur J Clin Microbiol Infect Dis. 2016; 35: 947-953
- Incidence and risk factors for pulmonary exacerbation treatment failures in patients with cystic fibrosis chronically infected with pseudomonas aeruginosa.Chest. 2012; 141: 485-493
- Epidemiology, pathophysiology, and prognostic implications of cystic fibrosis–related diabetes.Diabetes Care. 2010; 33: 2677
- Cystic fibrosis-related diabetes is caused by islet loss and inflammation.JCI Insight. 2018; 3: e98240
- Impaired insulin action in puberty.N Engl J Med. 1986; 315: 215-219
- The metabolic effects of pregnancy in cystic fibrosis.Obstetr Gynecol. 2005; 106
- Hepatic insulin resistance and defects in substrate utilization in cystic fibrosis.Diabetes. 1999; 48: 1082
- Pancreatic endocrine function in cystic fibrosis.J Pediatr. 1991; 118: 715-723
- Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis.J Cyst Fibros. 2007; 6: 101-109
- Incidence and risk factors for multiple antibiotic-resistant Pseudomonas aeruginosa in cystic fibrosis.Chest. 2007; 132: 562-568
- Continuous glucose monitoring indices predict poor FEV(1) recovery following cystic fibrosis pulmonary exacerbations.J Cyst Fibros. 2021;
- Cystic fibrosis-related diabetes in adults: inpatient management of 121 patients during 410 admissions.J Diabetes Sci Technol. 2012; 6: 1038-1044
- Carbohydrate intake and insulin requirement in children, adolescents and young adults with cystic fibrosis-related diabetes: a multicenter comparison to type 1 diabetes.Clin Nutr. 2015; 34: 732-738
- Why is insulin pump treatment rarely used in adolescents and young adults with cystic fibrosis-related diabetes?.Pediatr Diabetes. 2015; 16: 10-15
- Continuous glucose monitoring in cystic fibrosis - a practical guide.J Cyst Fibros. 2019; 18 (Supplement 2): S25-S31
- Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial.JAMA. 2017; 317: 371-378
- Continuous glucose monitoring vs conventional therapy for glycemic control in adults With Type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial.JAMA. 2017; 317: 379-387
- The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial.Diabetes Care. 2017; 40: 736
- Clinical care guidelines for cystic fibrosis–related diabetes.Diabetes Care. 2010; 33: 2697
- Relationship between glycosylated haemoglobin and mean plasma glucose concentration in cystic fibrosis.J Cyst Fibros. 2006; 5: 27-31
- Hemoglobin accurately predicts continuous glucose monitoring–derived average glucose in youth and young adults with cystic fibrosis.Diabetes Care. 2018; 41: 1406
- Accelerated red blood cell turnover can invalidate the use of hemoglobin A1c as a diagnostic test for cystic fibrosis related diabetes.Pediatr Res. 1999; 45: 90
- Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus.Pediatr Int. 1999; 41: 357-362
- Iron deficiency in cystic fibrosis: a cross-sectional single-centre study in a referral adult centre.Nutrients. 2022; 14
- Anemia in cystic fibrosis: incidence, mechanisms, and association with pulmonary function and vitamin deficiency.Nutr Clin Pract. 2008; 23: 557-563
- Implications of iron deficiency/anemia on the classification of diabetes using HbA1c.Nutr Diabetes. 2015; 5 (-e): e166
- Hyperglycemia and death in cystic fibrosis-related diabetes.Diabetes Care. 2011; 34: 1577-1578
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097
Kumar S.P.M., Soldatos G., Teede H.. PROSPERO 2021 CRD42021245817 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021245817. 2021.
- International consensus on use of continuous glucose monitoring.Diabetes Care. 2017; 40: 1631-1640
- ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.BMJ. 2016; 355: i4919
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634
- Use of an insulin pump combined with the FreeStyle Libre interstitial glucose monitor in a needle-phobic adolescent with cystic fibrosis-related diabetes.J Cyst Fibros. 2015; 14 (SUPPL): S142
- Cystic fibrosis related diabetes in an extremely young patient.J Cyst Fibros. 2007; 6: 247-249
- Sustained glycemic control with ivacaftor in cystic fibrosis-related diabetes.J Investig Med High Impact Case Rep. 2019; 72324709619842898
- Semaglutide in cystic fibrosis-related diabetes.J Clin Endocrinol Metab. 2020; 105
- Rapid progression to diabetes in a four-year-old girl with cystic fibrosis.Br J Biomed Sci. 2012; 69: 39-41
- Managing cystic fibrosis related diabetes patients on enteral feed: are we well equipped?.Diabet Med. 2011; 28 (SUPPL): 98
- Use of continuous subcutaneous insulin infusion in cystic fibrosis patients with cystic fibrosis-related diabetes awaiting transplantation.J Cyst Fibros. 2006; 5: 67-68
- Effectiveness of CHO-counting on glycometabolic control and comparison between the methods of I/CHO ratio calculation in subjects with cystic fibrosis-related diabetes (CFRD).Diabetes. 2019; : 68
- Glargine versus NPH insulin in cystic fibrosis related diabetes.J Cyst Fibros. 2008; 7: 134-136
- Continuous glucose monitoring as a useful decision-making tool for adults with cystic fibrosis.Internet J Pulm Med. 2014; 16
- Utility of an ultra-long acting insulin to treat cystic fibrosis related diabetes.J Cyst Fibros. 2015; 14 (SUPPL): S105
- A multi-disciplinary approach to glycaemic control in CFRD utilising continuous glucose monitoring (CGM): 571.Pediatr Pulmonol. 2013; 48: 417
- The impact of FreeStyle Libre flash glucose monitoring system on HbA1c in patients with cystic fibrosis-related diabetes.J Cyst Fibros. 2020; 19 (Supplement 2): S126
- The effects of a 10 week home-based supervised exercise training program in individuals with cystic fibrosis related diabetes.Pediatr Pulmonol. 2012; 47 (SUPPL): 372
- Use of continuous glucose monitoring in diagnosis and management of cystic fibrosis-related diabetes in children.J Diabetol. 2020; 11: 86-89
- WS15.4 early experience of flash glucose monitoring using the freestyle Libre system in adults with cystic fibrosis-related diabetes (CFRD) attending a large regional UK Centre.J Cyst Fibros. 2020; : 19
- The impact of continuous glucose monitoring on HbA1c in patients with cystic fibrosis related diabetes.J Cyst Fibros. 2017; 16 (Supplement): S148-S1S9
- Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosisrelated diabetes: a pilot study.Transpl Int. 2020; 33 (Supplement): 18
- Evolution of glycemia, insulinemia and glycosylated hemoglobin in a CF pediatric population.J Cyst Fibros. 2015; 14 (SUPPL): S103
- Use of the insulin pump in treat cystic fibrosis related diabetes.J Cyst Fibros. 2009; 8: 174-178
- The effect of CFTR modulators on the progression of cystic fibrosis-related diabetes.Pediatr Pulmonol. 2020; 55 (SUPPL): 84
- Effect of repaglinide therapy in adult patients with cystic fibrosis related diabetes.Pediatr Pulmonol. 2011; 46 (SUPPL): 405
- Improvement in diabetes control following the introduction of joint cystic fibrosis related diabetes clinics in adult patients.Diabet Med. 2017; 34 (Supplement): 10
- Impact of joint clinics on glycaemic control in individuals with cystic-fibrosis-related diabetes.Diabet Med. 2013; 30 (SUPPL.): 24
- Continuous glucose monitoring (CGM) for cystic fibrosis related diabetes (CFRD): sweet success or bitter disappointment?.Pediatr Pulmonol. 2012; 47 (SUPPL.): 420
- Efficacy and safety comparison of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes: systematic review and meta-analysis.Pol Arch Med Wewn. 2011; 121: 333-343
- Real-time continuous glucose monitoring in type 1 diabetes: a systematic review and individual patient data meta-analysis.Clin Endocrinol. 2017; 86 (Oxf): 354-360
- Beneficial effect of real-time continuous glucose monitoring system on glycemic control in type 1 diabetic patients: systematic review and meta-analysis of randomized trials.Eur J Endocrinol. 2012; 166: 567-574
- Systematic review and meta-analysis of the effectiveness of continuous glucose monitoring (CGM) on glucose control in diabetes.Diabetol Metab Syndr. 2013; 5: 39
- Effects of continuous glucose monitoring on metrics of glycemic control in diabetes: a systematic review with meta-analysis of randomized controlled trials.Diabetes Care. 2020; 43: 1146
- Real-time continuous glucose monitoring system for treatment of diabetes: a systematic review.Diabet Med. 2011; 28: 386-394
- Comparative analysis of the efficacy of continuous glucose monitoring and self-monitoring of blood glucose in type 1 diabetes mellitus.J Diabetes Sci Technol. 2012; 6: 1094-1102
- Systematic review of randomized controlled trials evaluating glycemic efficacy and patient satisfaction of intermittent-scanned continuous glucose monitoring in patients with diabetes.Diabetes Technol Ther. 2019; 22: 337-345
- Glucose depletion in the airway surface liquid is essential for sterility of the airways.PLoS One. 2011; 6: e16166
- Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients.J Cyst Fibros. 2014; 13: 478-484
- Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate with pulmonary function decline.J Cyst Fibros. 2018; 17: 783-790
- Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain.Diabetes Care. 2010; 33: 221-226
- Clinical Targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range.Diabetes Care. 2019; 42: 1593-1603
- Validation of time in range as an outcome measure for diabetes clinical trials.Diabetes Care. 2019; 42: 400-405
- Microvascular complications in cystic fibrosis–related diabetes.Diabetes Care. 2007; 30: 1056-1061
- Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.J Cyst Fibros. 2017; 16: 418-424
- Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H(+) secretion.Sci Rep. 2016; 6: 37955
- Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function.J Cyst Fibros. 2016; 15 (official journal of the European Cystic Fibrosis Society): 681-688
- Continuous glucose monitoring guided insulin therapy is associated with improved clinical outcomes in cystic fibrosis-related diabetes.J Cyst Fibros. 2018; 17: 798-803
- Continuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump.Diabetes Metab. 2010; 36: 409-413
Haliloglu B., Gokdemir Y., Atay Z., Abali S., Guran T., Karakoc F., et al. Hypoglycemia is common in children with cystic fibrosis and seen predominantly in females. 2017;18(7):607-13.
- Patterns and impact of hypoglycemia, hyperglycemia, and glucose variability on inpatients with insulin-treated cystic fibrosis-related diabetes.Diabetes Ther. 2016; 7: 575-582
- Effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes.Diabetes Care. 2011; 34: 795-800
- Continuous glucose monitoring: a review of successes, challenges, and opportunities.Diabetes Technol Ther. 2016; 18: S2.3-S2.13
- Continuous glucose monitoring systems for monitoring cystic fibrosis-related diabetes.Cochrane Database Syst Rev. 2021; 11Cd013755
- The effect of control IQ hybrid closed loop technology on glycemic control in adolescents and adults with cystic fibrosis-related diabetes.Diabetes Technol Ther. 2022; 24: 446-452
- Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: a pilot study.J Cyst Fibros. 2020; 19: 159-161
Article info
Publication history
Published online: July 27, 2022
Accepted:
July 20,
2022
Received in revised form:
June 20,
2022
Received:
April 7,
2022
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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- Early Glucose abnormalities in cystic fibrosis – how best to measure them, and what is to be done about them?Journal of Cystic FibrosisVol. 22Issue 1
- PreviewIn recent decades, two concepts have grown to increasing prominence in the field of cystic fibrosis related diabetes (CFRD). The first notion is that glucose abnormalities can be detected well before the diagnosis of CFRD can be made using current diagnostic criteria. The second concept is that it is biologically plausible that these glucose abnormalities may be of clinical importance to people with cystic fibrosis (via mechanisms that include increasing glucose in airway secretions [1], thereby promoting respiratory infections, as well as through catabolism from reduced secretion of insulin, a potent anabolic hormone [2].
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