Pregnant women treated with continuous subcutaneous insulin infusion have better glycemic control

Daniela Barros, postgraduate student of the Surgical Clinic Program at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP). Ribeirão Preto, SP, Brasil. 

Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications, such as spontaneous abortions, fetal malformations, macrosomia, preeclampsia, prematurity, cesarean section, and the worsening of complications related to DM itself, in addition to long-term repercussions on their offspring, such as a higher incidence of DM, obesity and cognitive alterations. 

Intensive glycemic control before conception and during pregnancy is essential to reduce the occurrence of these adverse outcomes (JENSEM, D.M., et al.; MARESH, M.J., et al.; LEPERCQ, J., et al.). Continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI) in this context, but data about the best option during pregnancy are limited. 

Thus, the main objective of this study named Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy – A Brazilian health care referral center cohort study, conducted at Universidade Federal de São Paulo and led by Juliana Ogassavara et al., was to compare the occurrence of maternal-fetal outcomes in pregnant women with T1D who were treated with CSII or MDI at a referral center of the public health network in São Paulo, Brazil. 

The authors observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control (OGASSAVARA, J. et al.).

One hundred and seventy-four pregnancies ofT1D patients were evaluated. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. 

The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest (OGASSAVARA, J. et al.).

Despite CSII has a number of advantages compared to MDI, such as greater flexibility of use, a more precise titration of the basal insulin dose and the type and size of the prandial boluses, a greater reduction of hypoglycemic episodes, improved glycemic control and improved quality of life, the results of this study are in agreement with the findings of other authors, whose studies evaluating pregnant women with T1D showed conflicting results or did not demonstrate major differences in maternal–fetal outcomes between the two treatment modalities (MANTAJ, U., et al.; KÖLHEDE, K., et al.; ZURAWSKA-KLIS, M.  et al.). 

For example, the most recent meta-analysis showed a lower HbA1c level with CSII vs. MDI in the first trimester (WMD: -0.45%; 95% CI: -0.62, -0.27), but this difference decreased in subsequent trimesters. Compared to MDI, CSII resulted in higher gestational weight gain (WMD: 1.02 kg; 95% CI: 0.41, 1.62) and lower daily insulin dose requirements in the first (SMD: -0.46; 95% CI: -0.68, -0.24) and subsequent trimesters. Moreover, infants from mothers in the CSII group were more likely to be LGA (RR: 1.16; 95% CI:1.07, 1.24) and less likely to be SGA (RR: 0.66; 95% CI: 0.45; 0.97) (RYS, P.M., et al.).

Imagem: Pixabay.

Another recent study involving 209 pregnant women, with 95 being treated with MDI and 114 treated with CSII, demonstrated no differences in the daily dose of insulin (both total and per kg of body weight), body mass index or weight gain. The 1st and 2nd trimester HbA1c levels were lower among the CSII group [6.83 (1.38) vs. 7.52 (2.11) %, p = 0.01 and 6.17 (0.9) vs. 6.57 (1.12) %, p = 0.009, respectively], while the 3rd trimester HbA1c level as well as the total change in HbA1c were comparable. 

There were also no differences in the gestational age at delivery, the mode of delivery, neonatal birth weight, or the rates of macrosomia, LGA or SGA. A higher Apgar score was noted among infants born to women in the CSII group [8.63 (1.63) vs. 8.03 (2.49), p = 0.047); however, the proportion of neonates with an Apgar score lower than 7 points was similar (ZURAWSKA-KLIS, M.  et al.).

It’s worth noting that in Brazil, access to treatment with CSII is very limited due to socioeconomic conditions. Most patients in the public health system can only receive CSII via a high-cost drug process or judicial process, and even private health insurance plans do not cover this type of treatment. 

Thus, those who have CSII treatment approved and funded by the government generally have more severe DM, with glycemic variability and hypoglycemia that are difficult to control even after optimized treatment with insulin analogs (BRASIL, 2018; BRASIL, 2020). Considering this context, the fact that the CSII group had outcomes like those to the MDI group can be interpreted as positive, according to the authors (OGASSAVARA, J. et al.).

In this present cohort, it is important to bounce that patients were not in adequate glycemic control in early pregnancy in either group. Despite suboptimal glycemic control in the sample, there was an improvement throughout pregnancy in both groups, showing that adequate follow-up plays an essential role in this issue, regardless of the route of insulin administration (OGASSAVARA, J. et al.).

Limitations of the study include the observational design and the low number of patients treated with CSII compared with those treated with MDI, which affects the power of the study. In addition, it was not possible to evaluate the total daily dose of insulin used, preconception HbA1c values and other parameters of glycemic control, such as time in range and the presence of hypoglycemia during pregnancy, since a small portion of patients had access to CGM in this sample. Furthermore, the evaluation was based on data from 2008 to 2021, and therefore, many patients used insulin pumps without sensor integration that are not comparable to the new models that are currently used (OGASSAVARA, J. et al.).

On the other hand, the strength of this study is that it represents a real-life cohort with fewer recall and information biases and is the first Brazilian study on this topic. Most of the published studies were carried out in Europe or in the United States, which does not represent the profile of our population and the public health system in Brazil (OGASSAVARA, J. et al.).

References

BRASIL. Ministério da Saúde. Protocolo Clínico e Diretrizes Terapêuticas do Diabete Melito Tipo 1 [online]. Biblioteca Virtual em Saúde – Ministério da Saúde. 2020 [viewed 24 November 2023]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/protocolo_clinico_terapeuticas_diabete_melito.pdf 

BRASIL. Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Gestão e Incorporação de Tecnologias em Saúde. Coordenação de Avaliação e Monitoramento de Tecnologias [online]. Portal Gov.br. 2018 [viewed 24 November 2023]. Available from: https://www.gov.br/conitec/pt-br/composicao/dgitis-departamento-de-gestao-e-incorporacao-de-tecnologias-em-saude/cmts-coordenacao-de-monitoramento-de-tecnologias-em-saude 

JENSEM, D.M., et al. Peri-conceptional A1C and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes. Diabetes Care [online]. 2009, vol. 32, no. 6, pp. 1046-8 [viewed 24 November 2023].  https://doi.org/10.2337/dc08-2061. Available from: https://pubmed.ncbi.nlm.nih.gov/19265024/ 

KÖLHEDE, K., et al. Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy – Pump vs multiple daily injections, a secondary analysis of an observational cohort study. Acta Obstet Gynecol Scand [online]. 2021, vol. 100, no. 5, pp. 927-33 [viewed 24 November 2023]. https://doi.org/10.1111/aogs.14039.  Available from: https://pubmed.ncbi.nlm.nih.gov/33176006/ 

LEPERCQ, J., et al. Determinants of a good perinatal outcome in 588 pregnancies in women with type 1 diabetes. Diabetes Metab [online]. 2019, vol. 45, no. 2, pp. 191-6 [viewed 24 November 2023].  https://doi.org/10.1016/j.diabet.2018.04.007. Available from:  https://pubmed.ncbi.nlm.nih.gov/29776801/ 

MARESH, M.J., et al. Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes. Diabetes Care [online]. 2015, vol. 38, no. 1, pp. 34-42 [viewed 24 November 2023].   https://doi.org/10.2337/dc14-1755. Available from: https://pubmed.ncbi.nlm.nih.gov/25368104/ 

OGASSAVARA, J. et al. Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy – A Brazilian health care referral center cohort study. Arch of Endocrinol Metab.  [online]. 2023, vol. 67, no. 6, pp. 1-8, e220483 [viewed 24 November 2023].  https://doi.org/10.20945/2359-4292-2022-0483. Available from: https://www.scielo.br/j/aem/a/9RnDgyvnJGw9HxGqdvJv44p/ 

RYS, P.M., et al. Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies. Eur J Endocrinol [online]. 2018, vol. 178, no. 5, pp. 545-563 [viewed 24 November 2023]. https://doi.org/10.1530/EJE-17-0804.  Available from: https://pubmed.ncbi.nlm.nih.gov/29545258/ 

ZURAWSKA-KLIS, M.  et al. Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes – Significance of pregnancy planning and pre pregnancy HbA1c. Diabetes Res Clin Pract [online]. 2021, vol. 172, pp. 108628 [viewed 24 November 2023].   https://doi.org/10.1016/j.diabres.2020.108628. Available from:  https://pubmed.ncbi.nlm.nih.gov/33358970/ 

To read the article, access

OGASSAVARA, J. et al. Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy – A Brazilian health care referral center cohort study. Arch of Endocrinol Metab [online]. 2023, vol. 67, no. 6, pp. 1-8, e220483 [viewed 24 November 2023].  https://doi.org/10.20945/2359-4292-2022-0483. Available from: https://www.scielo.br/j/aem/a/9RnDgyvnJGw9HxGqdvJv44p/

External links

Archives of Endocrinology and Metabolism – AEM: https://www.scielo.br/aem

Juliana Ogassavara – ORCID: https://orcid.org/0000-0003-4076-0963