Real-time continuous glucose monitoring reduces the duration of hypoglycemia episodes: a randomized trial in very low birth weight neonates
Florence Uettwiller, Aude Chemin, Elisabeth Bonnemaison, Géraldine Favrais, Elie Saliba, François Labarthe, Florence Uettwiller, Aude Chemin, Elisabeth Bonnemaison, Géraldine Favrais, Elie Saliba, François Labarthe
Abstract
Objectives: Hypoglycemia is frequent in very low birth weight (VLBW) neonates and compromises their neurological outcome. The aim of this study was to compare real-time continuous glucose monitoring system (RT-CGMS) to standard methods by intermittent capillary blood glucose testing in detecting and managing hypoglycemia.
Study design: Forty-eight VLBW neonates were enrolled in this prospective study. During their 3 first days of life, their glucose level was monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed hypoglycemia. Outcomes were the number and duration of hypoglycemic (≤ 50 mg/dl) episodes per patient detected by CGMS.
Results: Forty-three monitorings were analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia episodes than capillary blood glucose testing (1.2 ± 0.4 vs 0.4 ± 0.2 episode/patient, p<0.01). In the CGM-group, the use of RT-CGMS made it possible (i) to detect the same number of hypoglycemia episodes as blind-CGMS (1.2 ± 0.4 episode/patient), (ii) to adapt the glucose supply in neonates with hypoglycemia (increased supply during days 1 and 2), and (iii) to significantly reduce the duration of hypoglycemia episodes per patient (CGM 44[10-140] min versus IGM 95[15-520] min, p<0.05). Furthermore, it reduced the number of blood samples (CGM 16.9 ± 1.0 vs IGM 21.9 ± 1.0 blood sample/patient, p<0.001).
Conclusion: RT-CGMS played a beneficial role in managing hypoglycemia in VLBW neonates by adjusting the carbohydrate supply to the individual needs and by reducing the duration of hypoglycemia episodes. The clinical significance of the biological differences observed in our study need to be explored.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Figure 1. Flow chart.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4295867/bin/pone.0116255.g001.jpg)
![Figure 2. Number of hypoglycemic episodes per…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4295867/bin/pone.0116255.g002.jpg)
Figure 3. Comparison between IGM- and CGM-group:…
Figure 3. Comparison between IGM- and CGM-group: number of heel pricks, number and duration of…
Figure 4. Daily carbohydrate supplies in IGM-…
Figure 4. Daily carbohydrate supplies in IGM- and CGM-group.
Results, expressed as mean ± SE,…
- [Usefulness of continuous glucose monitoring system in detection of hypoglycaemic episodes in patients with diabetes in course of chronic pancreatitis].Ruxer J, Mozdzan M, Loba J, Barański M, Ruxer M, Markuszewski L. Ruxer J, et al. Pol Arch Med Wewn. 2005 Oct;114(4):953-7. Pol Arch Med Wewn. 2005. PMID: 16789520 Clinical Trial. Polish.
- Experience with Real-Time Continuous Glucose Monitoring in Newborns with Congenital Hyperinsulinemic Hypoglycemia.Anık A, Türkmen MK, Akcan AB, Ünüvar T, Öztürk S, Anık A. Anık A, et al. Z Geburtshilfe Neonatol. 2021 Apr;225(2):155-160. doi: 10.1055/a-1209-3861. Epub 2020 Aug 3. Z Geburtshilfe Neonatol. 2021. PMID: 32746476
- Monitoring the Frequency and Duration of Hypoglycemia in Preterm Infants and Identifying Associated Factors.Fernández Martínez MDM, Llorente JLG, de Cabo JM, López MAV, Porcel MDCO, Rubio JDD, Perales AB. Fernández Martínez MDM, et al. Fetal Pediatr Pathol. 2021 Apr;40(2):131-141. doi: 10.1080/15513815.2019.1692111. Epub 2019 Nov 18. Fetal Pediatr Pathol. 2021. PMID: 31738633
- Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring.Hay LC, Wilmshurst EG, Fulcher G. Hay LC, et al. Diabetes Technol Ther. 2003;5(1):19-26. doi: 10.1089/152091503763816427. Diabetes Technol Ther. 2003. PMID: 12725703
- Use of the Continuous Glucose Monitoring System to guide therapy in patients with insulin-treated diabetes: a randomized controlled trial.Tanenberg R, Bode B, Lane W, Levetan C, Mestman J, Harmel AP, Tobian J, Gross T, Mastrototaro J. Tanenberg R, et al. Mayo Clin Proc. 2004 Dec;79(12):1521-6. doi: 10.4065/79.12.1521. Mayo Clin Proc. 2004. PMID: 15595336 Clinical Trial.
- Dilemmas in parenteral glucose delivery and approach to glucose monitoring and interpretation in the neonate.Blanco CL, Smith V, Ramel SE, Martin CR. Blanco CL, et al. J Perinatol. 2023 Mar 24. doi: 10.1038/s41372-023-01640-5. Online ahead of print. J Perinatol. 2023. PMID: 36964206 Review.
- Geometry design for a fully insertable glucose biosensor with multimodal optical readout.Fine J, Coté GL, McShane MJ. Fine J, et al. J Biomed Opt. 2022 Nov;27(11):117001. doi: 10.1117/1.JBO.27.11.117001. J Biomed Opt. 2022. PMID: 36401344 Free PMC article.
- Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability.Musso V, Panfoli I, Battaglini M, Brigati G, Minghetti D, Andreato C, Ramenghi LA. Musso V, et al. Antioxidants (Basel). 2022 Sep 29;11(10):1945. doi: 10.3390/antiox11101945. Antioxidants (Basel). 2022. PMID: 36290668 Free PMC article.
- Neurocognitive Outcomes at Age 2 Years After Neonatal Hypoglycemia in a Cohort of Participants From the hPOD Randomized Trial.Edwards T, Alsweiler JM, Gamble GD, Griffith R, Lin L, McKinlay CJD, Rogers JA, Thompson B, Wouldes TA, Harding JE. Edwards T, et al. JAMA Netw Open. 2022 Oct 3;5(10):e2235989. doi: 10.1001/jamanetworkopen.2022.35989. JAMA Netw Open. 2022. PMID: 36219444 Free PMC article. Clinical Trial.
- Congenital hyperinsulinism in clinical practice: From biochemical pathophysiology to new monitoring techniques.Martino M, Sartorelli J, Gragnaniello V, Burlina A. Martino M, et al. Front Pediatr. 2022 Sep 23;10:901338. doi: 10.3389/fped.2022.901338. eCollection 2022. Front Pediatr. 2022. PMID: 36210928 Free PMC article. Review.
-
- Cornblath M, Schwartz R (1993) Hypoglycemia in the neonate. J Pediatr Endocrinol 6: 113–129. - PubMed
- Randomized Controlled Trial
- Blood Glucose / analysis*
- Blood Glucose Self-Monitoring / methods*
- Female
- Humans
- Hypoglycemia / diagnosis*
- Hypoglycemia / prevention & control
- Infant, Newborn
- Infant, Very Low Birth Weight
- Male
- Prospective Studies
- Treatment Outcome
- Blood Glucose
- Full Text Sources
- Other Literature Sources
- Medical
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![Figure 3. Comparison between IGM- and CGM-group:…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4295867/bin/pone.0116255.g003.jpg)
Figure 4. Daily carbohydrate supplies in IGM-…
Figure 4. Daily carbohydrate supplies in IGM- and CGM-group.
Results, expressed as mean ± SE,…
- [Usefulness of continuous glucose monitoring system in detection of hypoglycaemic episodes in patients with diabetes in course of chronic pancreatitis].Ruxer J, Mozdzan M, Loba J, Barański M, Ruxer M, Markuszewski L. Ruxer J, et al. Pol Arch Med Wewn. 2005 Oct;114(4):953-7. Pol Arch Med Wewn. 2005. PMID: 16789520 Clinical Trial. Polish.
- Experience with Real-Time Continuous Glucose Monitoring in Newborns with Congenital Hyperinsulinemic Hypoglycemia.Anık A, Türkmen MK, Akcan AB, Ünüvar T, Öztürk S, Anık A. Anık A, et al. Z Geburtshilfe Neonatol. 2021 Apr;225(2):155-160. doi: 10.1055/a-1209-3861. Epub 2020 Aug 3. Z Geburtshilfe Neonatol. 2021. PMID: 32746476
- Monitoring the Frequency and Duration of Hypoglycemia in Preterm Infants and Identifying Associated Factors.Fernández Martínez MDM, Llorente JLG, de Cabo JM, López MAV, Porcel MDCO, Rubio JDD, Perales AB. Fernández Martínez MDM, et al. Fetal Pediatr Pathol. 2021 Apr;40(2):131-141. doi: 10.1080/15513815.2019.1692111. Epub 2019 Nov 18. Fetal Pediatr Pathol. 2021. PMID: 31738633
- Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the results of continuous glucose monitoring.Hay LC, Wilmshurst EG, Fulcher G. Hay LC, et al. Diabetes Technol Ther. 2003;5(1):19-26. doi: 10.1089/152091503763816427. Diabetes Technol Ther. 2003. PMID: 12725703
- Use of the Continuous Glucose Monitoring System to guide therapy in patients with insulin-treated diabetes: a randomized controlled trial.Tanenberg R, Bode B, Lane W, Levetan C, Mestman J, Harmel AP, Tobian J, Gross T, Mastrototaro J. Tanenberg R, et al. Mayo Clin Proc. 2004 Dec;79(12):1521-6. doi: 10.4065/79.12.1521. Mayo Clin Proc. 2004. PMID: 15595336 Clinical Trial.
- Dilemmas in parenteral glucose delivery and approach to glucose monitoring and interpretation in the neonate.Blanco CL, Smith V, Ramel SE, Martin CR. Blanco CL, et al. J Perinatol. 2023 Mar 24. doi: 10.1038/s41372-023-01640-5. Online ahead of print. J Perinatol. 2023. PMID: 36964206 Review.
- Geometry design for a fully insertable glucose biosensor with multimodal optical readout.Fine J, Coté GL, McShane MJ. Fine J, et al. J Biomed Opt. 2022 Nov;27(11):117001. doi: 10.1117/1.JBO.27.11.117001. J Biomed Opt. 2022. PMID: 36401344 Free PMC article.
- Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability.Musso V, Panfoli I, Battaglini M, Brigati G, Minghetti D, Andreato C, Ramenghi LA. Musso V, et al. Antioxidants (Basel). 2022 Sep 29;11(10):1945. doi: 10.3390/antiox11101945. Antioxidants (Basel). 2022. PMID: 36290668 Free PMC article.
- Neurocognitive Outcomes at Age 2 Years After Neonatal Hypoglycemia in a Cohort of Participants From the hPOD Randomized Trial.Edwards T, Alsweiler JM, Gamble GD, Griffith R, Lin L, McKinlay CJD, Rogers JA, Thompson B, Wouldes TA, Harding JE. Edwards T, et al. JAMA Netw Open. 2022 Oct 3;5(10):e2235989. doi: 10.1001/jamanetworkopen.2022.35989. JAMA Netw Open. 2022. PMID: 36219444 Free PMC article. Clinical Trial.
- Congenital hyperinsulinism in clinical practice: From biochemical pathophysiology to new monitoring techniques.Martino M, Sartorelli J, Gragnaniello V, Burlina A. Martino M, et al. Front Pediatr. 2022 Sep 23;10:901338. doi: 10.3389/fped.2022.901338. eCollection 2022. Front Pediatr. 2022. PMID: 36210928 Free PMC article. Review.
-
- Cornblath M, Schwartz R (1993) Hypoglycemia in the neonate. J Pediatr Endocrinol 6: 113–129. - PubMed
- Randomized Controlled Trial
- Blood Glucose / analysis*
- Blood Glucose Self-Monitoring / methods*
- Female
- Humans
- Hypoglycemia / diagnosis*
- Hypoglycemia / prevention & control
- Infant, Newborn
- Infant, Very Low Birth Weight
- Male
- Prospective Studies
- Treatment Outcome
- Blood Glucose
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 4. Daily carbohydrate supplies in IGM-…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4295867/bin/pone.0116255.g004.jpg)
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