Parity increases insulin requirements in pregnant women with type 1 diabetes. Background Alterations in insulin requirements and insulin resistance during pregnancies complicated by diabetes constitute a challenge for both patients and clinicians. Pregnancies in women with type 1 diabetes are associated with an increased risk of congenital malformations, obstetric complications and neonatal morbidity, and this risk is directly correlated to glycemic control immediately before and during pregnancy. Thus, a tight glycemic control throughout pregnancy is crucial and can only be obtained if a successful collaboration between patients and clinicians is established. Aim The aim of the current study was to evaluate the insulin requirements in women with type 1 diabetes during pregnancy and to test whether parity affects insulin requirements. Method An observational cohort study was conducted. The cohort consisted of women with type 1 diabetes who gave birth at Aarhus University Hospital between January 2004 and December 2015. From the patients’ medical records, we obtained the following data at every visit: Daily insulin requirement (IU), current HbA1c, weight (kg), blood pressure, TSH level and weekly levothyroxine dose, if relevant. We also obtained the following pre-pregnancy data: weight (kg), height (cm), parity, daily insulin requirement (IU), last known HbA1c (not older than 6 months), duration of diabetes, use of insulin pump, medicine, smoking and alcohol habits, thyroid disease and measures of nephropathy and retinopathy. Daily insulin requirement was calculated by adding long-acting and short-acting insulin. The mean daily insulin requirement was determined at the following time points: pre-pregnancy (week 0), week 5-10, week 11-14, week 15-18, week 19-22, week 23-28, week 29-32, week 33-36 and week 37-40. Our primary outcome was: Mean daily insulin requirement (IU) at the above-mentioned time points. Secondary outcomes were i) Percentage decrease and increase from pre-pregnancy insulin requirement at the above-mentioned time points ii) The effect of parity on mean daily insulin requirement for the whole pregnancy iii) The effect of fetal gender on insulin requirement. Results 380 women with a total of 536 pregnancies were included in the study. The mean age was 31.1y and pre-pregnancy HbA1c 6,7 % (59,7 mmol/mol). Parity was: P0=43 %, P1=40 %, P2=14 % and P3+P4=3%. Insulin requirements from week 11-16 decreased significantly with 4% and rose significantly from week 19 to delivery with a peak of 70 % at week 33-36 (See Figure 1). Overall, insulin requirements increased significantly with parity; the unadjusted differences between P0 and P1, P2 and P3+4 were 9, 12 and 23% respectively and the adjusted (BMI, age, pre-pregnancy HbA1c and duration of diabetes) differences were 13, 20 and 36 %. We also observed difference between P1 and P3+4 at 20%. To confirm our results, we performed a subgroup analysis, where we only included the women who were in the cohort more than once (n=147). We compared mean daily insulin requirement in the woman's first pregnancy in the cohort with the following pregnancies. We found a significant difference in insulin requirement between the pregnancies of +11 % (9-13). This was across all parities. The Sex Ratio at Birth (live male newborns/total live newborns) was in our study 0,496 and we found no difference in mean daily insulin requirements when comparing women with male offspring and female offspring. Discussion In conclusion our data show that parity per se increases insulin requirements during pregnancy between 9 and 36 % in type 1 diabetes and confirm that insulin dosages exhibit a characteristic pattern with a modest early decrease and a pronounced late increase during pregnancy. Our study is to our knowledge the largest study on insulin requirements during pregnancy to date, which is an obvious strength and produces convincingly low p-values and narrow confidence intervals. This provides valuable information to achieve tight glycemic control throughout pregnancy. The large number of participants has yielded information on how the patients' parity affects insulin requirement and shows that the more times a women with type 1 diabetes gives birth the more insulin she needs. Being the first report to show this, our findings may have straight clinical implications for pregnant type 1 diabetes patients. Conflict of Interest Receipt of grants or research support: G.S and U.K. are supported by the Danish Diabetes Academy funded by the Novo Nordisk Foundation. P.O received financial support from the Novo Nordisk Foundation. The funding sources had no role in the study design, inclusion process, data analysis, statistical considerations or in the writing of this report.
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