In our observational study, which encompasses pregnant women with pT1D, we detected better glycaemic control on CSII than on MDI treatment, based on data evaluation from preconception through the trimesters till delivery. Moreover, the majority of pregnant women with pT1D achieved target glycaemic goals already in preconception and maintained them during the trimesters, using long-term CSII.
Data from previous studies focusing on glycaemic control in pregnant women with pT1D using different intensified insulin treatments (CSII or MDI) still remained inconsistent for superiority of either of them [4,5,6], partly because they did not focus on preconception monitoring or sustainability during the whole pregnancy. Moreover, glycaemic fluctuations, GV and hypoglycaemia, were suggested to influence the course of pregnancy in women with long-standing pT1D, but the effectiveness of different insulin treatments for glycaemic control and variability and hypoglycaemic episodes in pregnant women with pT1D has not been elucidated .
Some prior studies in this field revealed better glycaemic control with CSII treatment in complicated T1D during pregnancy , in line with our study results showing lower HbA1c levels among women with long-standing T1D and CSII.
A recently published meta-analysis comprising 47 predominantly non-interventional studies showed higher HbA1c reduction in early pregnancy, but this advantage was diminished in the second and third trimesters .
However, some previous investigations suggested a comparable effect of CSII and MDI on glycaemic control . Nevertheless, most of these available studies included pregnant women in the second trimester or the ones initiating pump treatment during actual pregnancy.
Moreover, a limited number of studies reported better preconception glycaemic control in women with pT1D on CSII compared with MDI treatment . Our results also confirmed a lower HbA1c level in preconception in women on CSII than in those on MDI treatment.
Although our women were not randomized to the MDI or CSII treatment arm, we tried to overcome potential bias by homogenizing groups in respect to age, duration of disease and treatment. In our study, in contrast to other studies on the topic, we followed pregnant women with long-standing T1D and a long-term use of either type of insulin treatment before pregnancy.
During pregnancy, we focused not only on HbA1c, having in mind it might not adequately reflect different aspects of glucose control, but also analysed acute glucose fluctuations or GV, which contribute to adverse pregnancy events . In addition, a better understanding of the pattern of blood glucose fluctuations in all three trimesters of pregnancy could make it easier to optimize glycaemic control in pregnant women with diabetes . In that context, in our study we used CV as an established parameter of GV. Pregnant women with pT1D on CSII treatment had a lower CV of fasting glycaemia in early pregnancy as well as after breakfast in late pregnancy (obtained from SMBG). In that context, our results might imply that assessing CV from SMBG, even without the use of a more sophisticated and recently established standard method of blood glucose measurement, might be useful and clinically relevant as a surrogate marker of GV. Furthermore, in a recently published meta-analysis a significant number of studies, nearly half of those included, used only SMBG as a glucose monitoring method .
In addition, our findings are in line with previously published studies showing no difference in mean FPG and PPG between CSII and MDI in the first and second trimesters [23,24,25]. However, according to our results, pregnant women with pT1D using CSII had lower mean PPG levels (after breakfast) in late pregnancy, which is an advantage in clinical settings. Moreover, besides better PPG regulation, a higher percentage of pregnant women with pT1D on CSII in our study reached the target value for the PPG goal in the third trimester after breakfast.
On the other hand, data on hypoglycaemic episodes in pregnant women with pT1D are quite limited. It has been shown that compared with MDI, CSII was associated with a slightly lower HbA1c level and a smaller risk of severe hypoglycaemia . Also, it is important to note that the effort to achieve better glycaemic control together with less GV could predispose to hypoglycaemia. Our results are in agreement with studies showing the superiority of CSII regarding fewer hypoglycaemic episodes during early pregnancy [1, 27], which is an important clinical challenge because pregnant women with pT1D are most vulnerable to hypoglycaemia in that period . As we have shown in this study, in respect to number of hypoglycaemia episodes per week, the majority of women on CSII were in the first tertile (rare hypoglycaemic events), which implies more stable glycaemic control with less GV and hypoglycaemia. In addition, the CSII group had lower TDD compared with MDI, in line with previously published data .
Current data on the relationship between glucose variability and adverse foetal outcome are still conflicting. Recent studies using CGM reported a correlation between parameters of glucose variability and foetal growth [29,30,31] in pregnant women with pT1D or gestational diabetes. Although earlier studies had conflicting results , in our study we demonstrated an availability of decreased glucose variability on CSII, even in clinical settings without the use of CGM, which might be of significant clinical relevance.
Concerning pregnancy outcomes, we could not demonstrate that CSII treatment induced a lower incidence of adverse pregnancy events compared with MDI therapy. The studies in this field gave conflicting results and, despite some positive results, most of the studies reported that optimal metabolic control during pregnancy does not always guarantee a favourable outcome [32, 33].
In addition, limitations of our study are the observational study design and use of a surrogate marker for glycaemic variability CV obtained by SMBG. Also, the relatively few adverse events are a limitation related to adequate evaluation of the incidence of adverse outcomes and do not allow formulating further conclusions.
Nonetheless, we demonstrated the advantages of long-term CSII on glucose control due to the lower level of HbA1c achieved already in preconception and maintained during the entire pregnancy. Also, we showed a diminished GV and less frequent hypoglycaemic episodes only in the first trimester on CSII, an aspect of glycaemic control insufficiently evaluated in previous investigations.