Real-World Insulin Treatment in Pregnant Women with Type 1 Diabetes Using an Advanced Hybrid Closed-Loop System

Abstract

To the Editor:

The achievement of strict glycemic control during pregnancy in women with type 1 diabetes (T1D) is essential to prevent pregnancy-related complications (such as congenital malformation, pre-eclampsia, and preterm delivery) and to reduce the risk of delivering infants large for gestational age (LGA).¹

Although continuous glucose monitoring (CGM) can help reaching targeted glucose levels,² only a minority of pregnant women achieved the glycemic and HbA_1c targets recommended by international guidelines.³

In recent years, the introduction of closed-loop insulin delivery systems has allowed a significant improvement in glycemic control in subjects with TID. The role that this new therapeutic modality may have in pregnant women with T1D is still uncertain.⁴

The aim of our retrospective single-center real-life analysis was to determine the outcomes on metabolic control, evaluated by CGM metrics, in eight pregnant women with long duration T1D (mean age 32.4 ± 4.5 years, duration of diabetes 19.6 ± 4.5 years, body mass index 23.7 ± 3.3 kg/m² and HbA_1c 6.8% ± 0.8%) treated with advanced hybrid closed-loop (aHCL) system Minimed™ 780G (Medtronic, Northridge, CA) and followed up in the diabetes unit of ASST Papa Giovanni XXIII (Bergamo, Italy) from August 2021 until October 2022. The study was approved by the ethics committee of ASST Papa Giovanni XXIII and informed written consent was obtained from all participants.

Of the eight enrolled patients, five women already using the aHCL system before pregnancy asked to continue with this therapy with the approval of the diabetes medical team, after detailed explanation of the off-label use of this system during pregnancy. Of the other three women, at the early stage of pregnancy (the switch to aHCL took place between the 8th and 13th gestational week), one was in therapy with hybrid closed-loop (HCL) system (Minimed 670G; Medtronic), one with continuous subcutaneous insulin infusion, and one with multiple daily injections (MDIs) therapy both with CGM (Dexcom G6 CGM System; Dexcom, San Diego, CA).

The indication for use of the aHCL system was the difficulty in achieving satisfactory glycemic control due to high glucose variability and frequent hypoglycemic episodes. The target glucose setpoint was 100 mg/dL (5.5 mmol/mol).

Data (obtained from the CareLink platform) regarding percentage of time spent in hypoglycemic (time below range [TBR] <63 mg/dL], euglycemic, and hyperglycemic (time above range >140 mg/dL) ranges, CGM-measured mean glucose concentration, glucose management indicator, and coefficient of variation were analyzed and discussed with all women monthly from 13 to 36 weeks. Nighttime was defined as the time between 00 and 06 a.m. and daytime defined as the time between 06 a.m. and 12 p.m.

CGM metrics and statistics in early pregnancy and throughout second to third trimesters are given in Table 1.

Table 1.

Monthly Changes in Continuous Glucose Monitoring Metrics in Eight Pregnant Women with Type 1 Diabetes Treated with an Advanced Hybrid Closed-Loop System from 13 to 36 Weeks of Pregnancy

	CGM data in early pregnancy		Second trimester			Third trimester
	0–8 Weeks	13–16 Weeks	17–20 Weeks	21–24 Weeks	25–28 Weeks	29–32 Weeks	33–36 Weeks
CGM metrics
Glucose management indicator %	6.6 ± 0.2	6.4 ± 0.3	6.4 ± 0.2	6.4 ± 0.3	6.4 ± 0.2	6.4 ± 0.3	6.3 ± 0.2
Sensor mean glucose (mg/dL)	142.6 ± 13.3	129 ± 10.1	128.8 ± 10	129.9 ± 12.6	128.3 ± 8.8	129.5 ± 11.2	124.3 ± 9.7
TIR % (63–140 mg/dL)	54.4 ± 7.7	64.3 ± 9.3	63.6 ± 8.6	63.4 ± 10	64.8 ± 8.5	64.8 ± 10.4	69.1 ± 8.5^a
TAR % (>140 mg/dL)	44 ± 8.5	33.6 ± 9.9	34.3 ± 9.4	34.9 ± 11.1	33.4 ± 8.5	33.9 ± 10.9	29.4 ± 9^a
TBR % (<63 mg/dL)	1.6 ± 1.8	2.1 ± 1.9	2.1 ± 1.9	1.7 ± 1.4	1.8 ± 2.2	1.3 ± 2	1.5 ± 2
Coefficient of variation, %	32.2 ± 3.8	33 ± 4.1	32.4 ± 3.2	31 ± 2.7	30.6 ± 4.6	30.2 ± 3	30.3 ± 4.5
Auto mode (Smart guard) %	n.a.	88.6 ± 17.7	98.1 ± 2.5	97.1 ± 6.1	98.5 ± 2.3	98.3 ± 2.7	95.8 ± 5.2
Insulin daily dose (U/kg)	0.6 ± 0.2	0.7 ± 0.2	0.7 ± 0.2	0.8 ± 0.3	0.9 ± 0.3	1 ± 0.4	1.1 ± 0.3
Insulin boluses %	58.6 ± 7.5	65.3 ± 4.9	62.4 ± 6.3	65.8 ± 5.6	67.8 ± 6.2	68.2 ± 6.9	69.8 ± 6.9
Insulin basal %	41.4 ± 7.5	34.7 ± 4.9	37.6 ± 6.3	34.2 ± 5.6	32.2 ± 6.2	31.8 ± 6.9	30.2 ± 6.9
Fingersticks calibrations (daily)	n.a.	3.3 ± 0.8	3 ± 1.2	3.1 ± 1.3	3.1 ± 1.2	3 ± 1.2	3.1 ± 1.5
CGM metrics—nighttime 00–06 a.m.
Sensor mean glucose (mg/dL)	n.a.	119.4 ± 14.1	124.8 ± 15.5	126.4 ± 16.2	121.6 ± 11.5	122.4 ± 15.5	115.5 ± 15.1
TIR % (63–140 mg/dL)	n.a.	73.3 ± 15	68.1 ± 16	68.8 ± 16.5	73.6 ± 11.6	73.9 ± 15.4	77.8 ± 13.9
TAR % (>140 mg/dL)	n.a.	24.5 ± 15.2	30.7 ± 16.8	30.3 ± 17.2	24.3 ± 12.1	24.3 ± 16.4	19.5 ± 14,4
TBR % (<63 mg/dL)	n.a.	2.2 ± 2.8	1.2 ± 1.2	0.9 ± 1.1	2.1 ± 4.1	1.8 ± 2.8	2.7 ± 3.7
Coefficient of variation, %	n.a.	28.7 ± 7.8	28.2 ± 3	25.7 ± 3.4	27.4 ± 6	26.5 ± 4.9	27 ± 6.9
CGM metrics—daytime 06 a.m.–12 p.m.
Sensor mean glucose (mg/dL)	n.a.	132.3 ± 10^b	130 ± 9.1	131.2 ± 12	130.5 ± 9.2^b	132 ± 10.5^b	127.2 ± 8.8^b
TIR % (63–140 mg/dL)	n.a.	61.1 ± 9^b	62.2 ± 7.6	61.2 ± 2.2	61.9 ± 9^b	61.3 ± 9.3^b	66.1 ± 8^b
TAR % (>140 mg/dL)	n.a.	36.9 ± 9.5	35.5 ± 8	36.5 ± 10.3	36.3 ± 9.1^b	37.1 ± 9.9^b	32.5 ± 8.1^b
TBR % (<63 mg/dL)	n.a.	2 ± 1.5	2.3 ± 2	2.3 ± 1.9	1.8 ± 1.6	1.6 ± 1.5	1.4 ± 1.6
Coefficient of variation, %	n.a.	33.9 ± 3.5	33.6 ± 3.6^b	32.1 ± 3^b	31.2 ± 4.3^b	30.9 ± 2.7^b	30.4 ± 4

Data are expressed as mean ± SD. Differences between CGM metrics were analyzed by ANOVA for repeated measure.

P < 0.05 versus all the previous months.

P < 0.05 during daytime versus nighttime in the corresponding pregnancy period.

CGM, continuous glucose monitoring; TAR, time above range; TBR, time below range.

TBR was very low throughout all trimesters and TIR was always >60% and close to 70% in the period between 33 and 36 weeks. No episodes of ketoacidosis were registered.

Regarding obstetric and fetal outcomes, mean neonatal weight was 3537 ± 483 g, and only one woman delivered preterm before 37 gestational weeks. The percentage of LGA newborns was 50% similar to that reported in previous studies for pregnant women on MDIs or sensor-augmented pump therapy.⁵

Our real-world retrospective analysis, despite the small size examined, shows that the aHCL system was safe with a very low TBR throughout pregnancy. The use of the aHCL system may improve CGM metrics in pregnant women with long-lasting T1D unwilling to stop aHCL therapy during pregnancy or with an unsatisfactory glycemic control with other insulin therapies. However, there are still several challenges with the use of the aHCL system Minimed 780G (Medtronic). It would be important to be able to set the glycemic target <100 mg/dL, and a more aggressive automatic corrections with insulin boluses may be helpful to maintain the very tight range of glycemic levels essential to reduce adverse pregnancy outcomes.

Footnotes

Authors' Contributions

A.R.D. designed and coordinated the study, analyzed data, and wrote and revised the article; N.D.B. analyzed data and wrote the article; G.L. and S.B. analyzed data; A.C., C.S., and R.B. enrolled patients and analyzed data; R.T. edited and revised the article. All authors have contributed to and approved the final version of the article.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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