Evaluation of glycaemic profile variability as a basis for insulin therapy strategy in pregnant women with type 1 diabetes
https://doi.org/10.14341/DM10214
Abstract
BACKGROUND: Patients with any form of diabetes during pregnancy should achieve the target (close to physiological) values of glycaemia, the main condition for a safe course and outcomes of pregnancy. To accomplish this task, effective and safe methods of insulin therapy should be selected.
AIM: To determine the glycaemic profile and pregnancy outcomes in women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) and multiple insulin injections (MII).
METHODS: A continuous glucose monitoring (CGM) of 100 pregnant women with type 1 diabetes treated with CSII and 100 women treated with MII was conducted to assess the effectiveness of these insulin therapy regimens in achieving target blood glucose values.
RESULTS: HbA1c levels were significantly lower during the first, second, and third trimesters in patients treated with CSII than those treated with MII. Glucose variability has already improved since the second trimester of pregnancy in women treated with CSII, which was not observed in those treated with MII. The period of hyperglycaemia according to the results in pregnant women treated with CSII was 25 [13; 38] %, which was lower than those treated with MII, 41 [18; 54] %. No risk of obstetric and perinatal complications was observed with the duration of the hyperglycaemic state of <25% of the CGM time, whereas the risk of neonatal hypoglycaemia appeared with the duration of the hypoglycaemic state of a mother with type 1 diabetes of >0.2%. The relationship between glucose variability in terms of MAGE and MODD and the risk of developing macrosomia has been observed, and the dependence of glucose variability (MODD and CONGA) and the risk of neonatal hypoglycaemia and preeclampsia have also been confirmed.
CONCLUSION: Comprehensive assessment of the glycaemic profile when using CSII, confirmed the advantages of using CSII in pregnant women with type 1 diabetes to achieve the target glycaemia values, to reduce glucose variability and duration of hypoglycaemic episodes, which led to decreased frequency of obstetric and perinatal complications.
Keywords
type 1 diabetes mellitus,
pregnancy,
continuous subcutaneous insulin infusion,
continuous glucose monitoring,
glucose variability
Supporting agencies: The work was carried out as part of: “Intensive insulin therapy of various types of diabetes mellitus during pregnancy, childbirth and the postpartum period” No. AAAA-A18-118011140016-2 (fundamental topic, 2018); “The effect of various types of insulin therapy of type I diabetes on the course and outcome of pregnancy” No. AAAA-A17-117042510409-2 (search topic, 2018); “Development of a rational strategy for the management of the preconception, gestational and postnatal periods, as well as a model for predicting and preventing perinatal complications to ensure safe delivery in high-risk groups,” a fundamental topic of research for 2019/2021: state number. Registration AAAA-A19-119030490046-1.
About the Authors
Alena V. Tiselko
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott
Russian Federation
Russian Federation
MD, PhD, senior research associate
Maria I. Yarmolinskaya
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott
Russian Federation
Russian Federation
MD, PhD, Professor
Elena V. Misharina
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott
Russian Federation
Russian Federation
MD, PhD, senior research associate
Yuliya P. Milyutina
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott
Russian Federation
Russian Federation
PhD in Biology, senior research associate
References
1. Murphy HR, Bell R, Cartwright C, et al. Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study. Diabetologia. 2017;60(9):1668–1677. doi: https://doi.org/10.1007/s00125-017-4314-3
2. Patterson CC, Dahlquist GG, Gyürüs E, et al.; EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–2020: a multicentre prospective registration study. Lancet. 2009;373(9680):2027–2033. doi: https://doi.org/10.1016/S0140-6736(09)60568-7
3. Feig DS, Hwee J, Shah BR, et al. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996–2010. Diabetes Care. 2014;37(6):1590–1596. doi: https://doi.org/10.2337/dc13-2717
4. Баранов В.Г., Соколоверова И.М. Достижения советской клинической диабетологии за 50 лет // Проблемы эндокринологии. — 1967. — Т. 13. — №5. — С. 35–40. [Baranov VG, Sokoloverova IM. Dostizheniya sovetskoy klinicheskoy diabetologii za 50 let. Probl Endokrinol (Mosk). 1967;13(5):35–40. (In Russ.)]
5. Barnett DM, Barnett LP. The history of diabetes. In: Kahn BB, King GL, Moses AC, et al. editors. Joslin’s diabetes mellitus. Philadelphia: Lippincott Williams Wilkins; 2005. Р. 1–17.
6. Айламазян Э.К., Боровик Н.В., Потин В.В., Тиселько А.В. Подготовка женщин с сахарным диабетом к беременности // Доктор Ру. — 2014. — №12. — C. 34–38. [Ailamazian EK, Borovik NV, Potin VV, Tiselko AV. Preparing women with diabetes for pregnancy. Doktor.ru. 2014;(12):34–38. (In Russ.)]
7. Damm P, Mersebach H, Rastam J, et al. Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester. J Matern Fetal Neonatal Med. 2014;27(2):149–154. doi: https://doi.org/10.3109/14767058.2013.806896
8. Borg R, Kuenen JC, Carstensen B, et al.; ADAG Study Group. Associations between features of glucose exposure and A1C: the A1C-Derived Average Glucose (ADAG) Study. Diabetes. 2010;59(7):1585–1590. doi: https://doi.org/10.2337/db09-1774
9. Айламазян Э.К., Абашова Е.И., Аржанова О.Н., и др. Сахарный диабет и репродуктивная система женщины: руководство для врачей / Под ред. Э.К. Айламазяна. — М.: ГЭОТАР-Медиа, 2017. — 428 с. [Aylamazyan EK, Abashova EI, Arzhanova ON, et al. Sakharnyy diabet i reproduktivnaya sistema zhenshchiny: rukovodstvo dlya vrachey. Ed. by Aylamazyan EK. Moscow: GEOTAR-Media; 2017. 428 р. (In Russ.)]
10. Feldman AZ, Brown FM. Management of type 1 diabetes in pregnancy. Curr Diab Rep. 2016;16(8):76. doi: https://doi.org/10.1007/s11892-016-0765-z
11. Beck RW, Riddlesworth T, Ruedy K, et al.; DIAMOND Study Group. 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(4):371–378. doi: https://doi.org/10.1001/jama.2016.19975
12. Chen T, Xu F, Su JB, et al. Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance. Diabetol Metab Syndr. 2013;5:38. doi: https://doi.org/10.1186/1758-5996-5-38
13. Bolinder J, Antuna R, Geelhoed-Duijvestijn P, et al. Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial. Lancet. 2016;388 (10057):2254–2263. doi: https://doi.org/10.1016/S0140-6736(16)31535-5
14. Feig DS, Asztalos E, Corcoy R, et al.; CONCEPTT Collaborative Group. CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: a multi-center, multi-national, randomized controlled trial — study protocol. BMC Pregnancy Childbirth. 2016;16(1):167. doi: https://doi.org/10.1186/s12884-016-0961-5
15. Feig DS, Murphy HR. Continuous glucose monitoring in pregnant women with type 1 diabetes: benefits for mothers, using pumps or pens, and their babies. Diabet Med. 2018;35(4):430–435. doi: https://doi.org/10.1111/dme.13585
16. Dalfrà MG, Sartore G, Di Cianni G, et al. Glucose variability in diabetic pregnancy. Diabetes Technol Ther. 2011;13(8):853–859. doi: https://doi.org/10.1089/dia.2010.0145
17. Secher AL, Ringholm L, Andersen HU, et al. The effect of real-time continuous glucose monitoring in pregnant women with diabetes: a randomized controlled trial. Diabetes Care. 2013;36(7):1877–1883. doi: https://doi.org/10.2337/dc12-2360
18. Misso ML, Egberts KJ, Page M, et al. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010;(1):CD005103. doi: https://doi.org/10.1002/14651858.CD005103.pub2
19. Melidonis A, Kamaratos A, Angelidi A, et al. The impact of continuous subcutaneous insulin infusion therapy on efficacy and safety in a cohort of type 1 diabetes patients: a 3-year prospective study. Diabetes Technol Ther. 2016;18(3):159–163. doi: https://doi.org/10.1089/dia.2015.0309
20. Volpe L, Pancani F, Aragona M, et al. Continuous subcutaneous insulin infusion and multiple dose insulin injections in type 1 diabetic pregnant women: a case-control study. Gynecol Endocrinol. 2010;26(3):193–196. doi: https://doi.org/10.1080/09513590903215540
21. Farrar D, Tuffnell DJ, West J, West HM. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev. 2016;(6):CD005542. doi: https://doi.org/10.1002/14651858.CD005542.pub3
22. Mukhopadhyay A, Farrell T, Fraser RB, Ola B. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials. Am J Obstet Gynecol. 2007;197(5):447–456. doi: https://doi.org/10.1016/j.ajog.2007.03.062
23. Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 8-й вып. // Сахарный диабет. — 2017. — Т. 20. — №1S. — C. 1–121. [Dedov II, Shestakova MV, Mayorov AY, et al. Standards of specialized diabetes care. Ed. by Dedov II, Shestakova MV, Mayorov AY. 8th ed. Diabetes Mellitus. 2017;20(1S):1–121. (In Russ.)] doi: https://doi.org/10.14341/DM20171S8
24. Satya Krishna SV, Kota SK, Modi KD. Glycemic variability: clinical implications. Indian J Endocrinol Metab. 2013;17(4):611–619. doi: https://doi.org/10.4103/2230-8210.113751
25. McCall AL, Kovatchev BP. The median is not the only message: a clinician’s perspective on mathematical analysis of glycemic variability and modeling in diabetes mellitus. J Diabetes Sci Technol. 2009;3(1):3–11. doi: https://doi.org/10.1177/193229680900300102
26. Сухих Г.Т., Ходжаева З.С., Филиппов О.С., и др. Федеральные клинические рекомендации. Гипертензивные расстройства во время беременности, в родах и послеродовом периоде. Преэклампсия. Эклампсия. — М., 2013. — 85 с. [Sukhikh GT, Khodzhayeva ZS, Filippov OS, i dr. Federal clinical guidelines. Gipertenzivnyye rasstroystva vo vremya beremennosti, v rodakh i poslerodovom periode. Preeklampsiya. Eklampsiya. Moscow; 2013. 85 р. (In Russ).]
27. Дементьева Г.М. Оценка физического развития новорожденных: пособие для врачей. — М., 2000. — 25 с. [Dement’yeva GM. Otsenka fizicheskogo razvitiya novorozhdennykh: posobiye dlya vrachey. Moscow; 2000. 25 р. (In Russ.)]
28. Monnier L, Wojtusciszyn A, Colette C, Owens D. The contribution of glucose variability to asymptomatic hypoglycemia in persons with type 2 diabetes. Diabetes Technol Ther. 2011;13(8):813–818. doi: https://doi.org/10.1089/dia.2011.0049
29. Hirsch IB. Glycemic variability and diabetes complications: does it matter? Of course it does! Diabetes Care. 2015;38(8):1610–1614. doi: https://doi.org/10.2337/dc14-2898
Supplementary files
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2. Fig. 1. Daily doses of insulin in the I, II, and III trimesters of pregnancy in women with type 1 diabetes mellitus, using continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0.05; *** - p <0.001 - differences between MII and FDI in the corresponding trimesters of pregnancy). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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3. Fig. 2. Dynamics of glycated hemoglobin level during pregnancy in women with type 1 diabetes mellitus, using the regimes of continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0.05; ** - p <0.01 ; *** - p <0.001 - differences between MII and FDI in the corresponding trimesters of pregnancy). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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4. Fig. 3. Indicators of the duration of hyperglycemia in the I, II and III trimesters of pregnancy according to the results of continuous monitoring of glucose in women who used the regimes of continuous subcutaneous insulin infusion (PPII) and multiple injections of insulin (MII) (* - p <0.05; ** - p <0.01 - the difference between the indicator in the MII group and the FDI in the corresponding trimester; # - p <0.05 - the difference between the indicator and its value in the I trimester in the corresponding group). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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5. Fig. 4. Indicators of the duration of hypoglycemic conditions in the I, II and III trimesters of pregnancy based on continuous monitoring of glucose in women with type 1 diabetes mellitus, using the regimes of continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0, 05; ** - p <0.01 - difference between the indicator in the MII group and the FDI in the corresponding trimester). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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6. Fig. 5, A. Indicators of the MAGE index in I, II, and III trimesters of pregnancy in women with type 1 diabetes mellitus, using the regimes of continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0.05 - difference between the indicator in the MII group and the FDI in the corresponding trimester). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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7. Fig. 5, B. MODD index values in the I, II, and III trimesters of pregnancy in women with type 1 diabetes mellitus, using continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0.05 - difference in group of MII from FDI in the corresponding trimester). (For comparison, the Mann – Whitney test was used. The data are presented as medians; the boundaries of the “box” are 25 and 75 percentiles; the “mustache” is the minimum and maximum values in the sample.) | |
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8. Fig. 5, B. The indicators of the CONGA index in I, II and III trimesters of pregnancy in women with type 1 diabetes mellitus, using continuous subcutaneous insulin infusion (PPII) and multiple insulin injections (MII) (* - p <0.05 - difference in MII group from the group of FDI in the corresponding trimester; # - p <0.05 - the difference between the indicator and its value in the first trimester in the corresponding group). (For comparison, the Mann – Whitney test was used. The data are presented as medians, the boundaries of the “box” are 25 and 75 percentiles, and the “mustache” is the minimum and maximum values in the sample.) | |
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9. Таблица1 | |
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For citations:
Tiselko A.V., Yarmolinskaya M.I., Misharina E.V., Milyutina Yu.P. Evaluation of glycaemic profile variability as a basis for insulin therapy strategy in pregnant women with type 1 diabetes. Diabetes mellitus. 2019;22(6):526-535. (In Russ.) https://doi.org/10.14341/DM10214
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