Our data show that pregnant women with pregestational T2DM have a higher incidence of spontaneous abortion (within the 24th week of gestation) than women with pregestational T1DM and that it is correlated with the pregestational BMI and the ∆_total insulin requirement of the first trimester. In addition, we found that women with pregestational T1DM have a higher incidence of perinatal complications, such as LGA, than T2DM and it is correlated with the higher weight gain during pregnancy.
The differences in patient backgrounds, such as longer duration of diabetes, higher insulin requirement at early gestation, higher incidence of retinopathy and nephropathy in women with T1DM, and higher pregestational BMI and weight in women with T2DM are in line with those reported in other studies [8, 9].
In the current study women with T2DM had a higher incidence of spontaneous abortion and it was correlated with pregestational BMI and ∆_total insulin requirement of the first trimester. These findings suggest that obesity and consequent decrease of insulin sensitivity during the first trimester of pregnancy increase the risk of obstetrical complications. As known, women with T1DM need a net reduction in insulin dose in early and late gestation and about a 20% increase in the second and third trimesters . By contrast, women with T2DM require a much greater increase in insulin dose from the start to the end of each trimester with a progressive increase. Although the increase in insulin requirement is presumably due to the effects of the placental hormones, some factors may have an influence in determining insulin requirement during pregnancy, such as pregestational BMI. An increase in adiposity is associated with higher production of pro-inflammatory cytokines and adipokines, which are responsible for the changes in insulin sensitivity .
Previous studies have shown that T2DM is associated with higher incidence of early and late spontaneous abortion and in turn spontaneous abortion is associated with a high risk of developing T2DM . T2DM, like other cardiovascular risk factors, is associated with endothelial dysfunction and therefore with placenta abnormalities [12, 13]. The pregnancies of women with T2DM are known to be more prone to a higher risk of perinatal death, as well as congenital malformations, than those of women with T1DM . In a study conducted by Clausen and colleagues, 61 women with T2DM were compared with 240 women with T1DM, demonstrating a 4 to 9 times higher incidence of foetal perinatal death in women of the first group compared to the second, although the latter had worse metabolic compensation . These data were also confirmed by a recent meta-analysis of 33 observational studies published in the last 20 years, where women with T2DM have a higher incidence of perinatal death despite having a lower duration of diabetes, lower HbA1c values and lower rates of diabetic complications at the time of pregnancy than T1DM . By contrast, McGrogan and colleagues found a similar frequency of spontaneous abortion in women with T2DM and women with T1DM, despite being greater than 20% compared to the general population . In the current study, pregestational HbA1c was not associated with perinatal complications in women with T2DM and T1DM, even though pregestational maternal glycaemic control is known to reduce perinatal complications in pregnant women with diabetes, and current guidelines recommend a similar treatment strategy for both women with T1DM and T2DM . A recent meta-analysis has shown that despite less severe glycaemic disturbance, women with T2DM did not have better perinatal outcomes than those with T1DM, suggesting that factors other than glycaemic control also affect perinatal complications in women with T2DM . Indeed, pregnancy-induced insulin resistance adds to the pre-existing insulin resistance, typical of T2DM, and the pre-existing pancreatic β-cell defect compromises the ability to enhance insulin secretion during pregnancy, leading to marked hyperglycaemia . Pregnancy-induced metabolic changes in women with T2DM require more intensive monitoring and closer titration of treatment. Unlike normal pregnancies, which in the first trimester tend to have lower glucose values, in pregnant women with T2DM higher glucose spikes are generally observed and strict insulin therapy adjustment is required .
Taken together, the above findings regarding pregnancy in T2DM on a background of metabolic syndrome suggest that obesity and insulin resistance before and during the first trimester of pregnancy may greatly influence the risk of perinatal complications, more than glycaemic control [13, 16, 18].
With regard to women with T1DM, in the present study about 50% of them had perinatal/neonatal complications such as LGA and consequently higher birth weight percentiles and this percentage was higher than in women with T2DM, in line with other studies . We found LGA was correlated with maternal weight gain during pregnancy, rather than pregestational HbA1c. Similar results were obtained in a Danish observational study, carried out on a group of 115 women with T1DM, which demonstrated that weight gain was an independent risk factor for foetal overgrowth . In addition, a retrospective analysis of pregnant women with T1DM showed that excess weight gain was correlated with high risk of LGA . Other studies showed that, in addition to weight increase, HbA1c values also correlated with the risk of LGA. In a study conducted by Morrens and colleagues, out of 180 pregnant women with T1DM, there was an increased frequency of LGA equal to about 42.5% of cases, certainly a higher incidence than that of the general population, correlating this finding with both weight gain and HbA1c values in early gestation and at delivery . This result can be explained by longer duration of diabetes, greater glycaemic instability  and, according to other studies, greater weight of the placenta  in women with T1DM compared to women with T2DM. Also worthy of note is the need for greater surveillance for hypoglycaemias in LGA infants of women with T1DM given the 2.5-fold greater risk for these infants of hypoglycaemia. This factor can be considered a better predictor of neonatal hypoglycaemia, compared to maternal glycaemic control . It has been suggested that glycaemic fluctuations and hypoglycaemia may influence the course of pregnancy in women with long-standing T1DM, but the effectiveness of different insulin treatments for glycaemic control and variability and hypoglycaemic episodes in pregnant women with T1DM has not been elucidated [25, 26]. In the current study no differences were found in the prevalence of hypoglycaemia between women with T1DM and T2DM.
The present study has limitations. First, our study had a retrospective cross-sectional design. Second, the sample size was small. Because of these limitations, the results of the present study should be carefully interpreted. Nonetheless, we believe that our findings have an important implication for clinical management and treatment of pregnant women with diabetes. To confirm our findings, future studies with a prospective design and larger sample size including women with and without perinatal complications are warranted.
In conclusion, women with T1DM have a higher risk of LGA than T2DM due to the weight gain throughout pregnancy. By contrast, women with T2DM have a higher risk of spontaneous abortion than T1DM, due to pregestational BMI and ∆_total insulin requirement in the first trimester. Management of pregnancy complicated by diabetes mellitus is challenging for both the health care provider and the patient. Despite the efforts and results obtained over the past decades, maternal foetal outcomes still continue to be worse than those not complicated by diabetes mellitus.