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      Evaluation of Glycaemic Control, Glucose Variability and Hypoglycaemia on Long-Term Continuous Subcutaneous Infusion vs. Multiple Daily Injections: Observational Study in Pregnancies With Pre-Existing Type 1 Diabetes

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          Abstract

          Introduction

          We evaluated the effectiveness of long-term continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin (MDI) injections for glycaemic control and variability, hypoglycaemic episodes and maternal/neonatal outcomes in pregnant women with pre-existing type 1 diabetes (pT1D).

          Methods

          Our observational cohort study included 128 consecutive pregnant women with pT1D, who were treated from 1 January 2010 to 31 December 2017. Of 128 participants, 48 were on CSII and 80 were on MDI. Glycaemic control was determined by glycated haemoglobin (HbA1c) (captured in preconception and each trimester of pregnancy). Glucose variability (GV) was expressed as the coefficient of variation (CV) [calculated from self-monitoring of blood glucose (SMBG) values], and hypoglycaemia was defined as glucose values < 3.9 mmol/l. The data on maternal and neonatal outcomes were collected from obstetrical records.

          Results

          Duration of the treatment was 8.8 ± 5.3 years in the CSII and 12.6 ± 8.0 years in the MDI group. The CSII lowered HbA1c in preconception (7.1 ± 0.1 vs. 7.9 ± 0.2%, p = 0.03) and the first (6.9 ± 0.1 vs. 7.7 ± 0.2%, p = 0.02), second (6.6 ± 0.1 vs. 7.2 ± 0.1%, p = 0.003) and third (6.5 ± 0.1 vs. 6.8 ± 0.1%, p = 0.02) trimesters significantly better than MDI. Significantly lower CV was observed only for fasting glycaemia in the first trimester (17.1 vs 28.4%, p < 0.001) in favour of CSII. Moreover, the CSII group had significantly lower mean hypoglycaemic episodes/week/patient only during the first trimester (2.0 ± 1.7 vs 4.8 ± 1.5, p < 0.01). In early pregnancy, the majority of women on CSII had less hypoglycaemia than on MDI (0–3: 79.1 vs. 29.1%; 4–6: 18.8 vs. 65.8%; ≥ 7: 2.1 vs. 5.1%, p < 0.01, respectively). We found no difference in the incidence of adverse maternal/neonatal outcomes.

          Conclusions

          Treatment with CSII resulted in a favourable reduction of HbA1c in the preconception period and each trimester in pregnancy. Moreover, long-term CSII treatment demonstrated more stable metabolic control with less GV of fasting glycaemia and fewer hypoglyacemic episodes only during early pregnancy.

          Electronic supplementary material

          The online version of this article (10.1007/s13300-020-00780-7) contains supplementary material, which is available to authorized users.

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          Most cited references25

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          Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion.

          Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycaemia in Type 1 diabetes, but the change in hypoglycaemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta-analysis comparing severe hypoglycaemia and glycaemic control during CSII and MDI. Databases and literature (1996-2006) were searched for randomized controlled trials (RCTs) and before/after studies of > or = 6 months' duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years on MDI. In 22 studies (21 reports), severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycaemia rates on MDI (P < 0.001). The mean difference in glycated haemoglobin (HbA(1c)) between treatments was less for RCTs [0.21% (0.13-0.30%)] than in before/after studies [0.72% (0.55-0.90%)] but strongly related to the initial HbA(1c) on MDI (P < 0.001). The severe hypoglycaemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycaemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA(1c) was in those with the highest HbA(1c) on MDI.
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            Peri-Conceptional A1C and Risk of Serious Adverse Pregnancy Outcome in 933 Women With Type 1 Diabetes

            OBJECTIVE To study the association between peri-conceptional A1C and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). RESEARCH DESIGN AND METHODS Prospective data were collected in 933 singleton pregnancies complicated by type 1 diabetes. RESULTS The risk of serious adverse outcome at different A1C levels was compared with the background population. The risk was significantly higher when peri-conceptional A1C exceeded 6.9%, and the risk tended to increase gradually with increasing A1C. Women with A1C exceeding 10.4% had a very high risk of 16%. Congenital malformation rate increased significantly at A1C above 10.4%, whereas perinatal mortality was increased even at A1C below 6.9%. CONCLUSIONS These results support recent guidelines of preconceptional A1C levels <7% in women with type 1 diabetes.
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              Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus.

              To assess the relation between glycaemic control in early pregnancy and the risk of congenital malformations in offspring of mothers with Type I (insulin-dependent) diabetes mellitus. From 1988-1997, we prospectively collected data from 691 pregnancies and 709 offspring of 488 women with Type I diabetes in a specific geographic area in Southern Finland. Glycated haemoglobin A1c at less than 14 weeks of gestation was used as the indicator of glycaemic control. The malformations were diagnosed either by ultrasonography in pregnancy or during the neonatal period. We also studied 729 non-selected control pregnancies in women without diabetes. The numbers of major fetal malformations were 30 (4.2%) in patients with Type I diabetes and 10 (1.2%) in the control subjects (relative risk 3.1; 95% confidence interval: 1.6 to 6.2). Even women whose HbA1c was only slightly raised (5.6 to 6.8%, i.e. 2.0 to 5.9 standard deviation units) showed a relative risk of 3.0 (95% confidence interval: 1.2 to 7.5). Haemoglobin A1c retained its statistically significant association with the occurrence of malformations after adjusting for White's class, age at onset of diabetes, duration of diabetes, parity, smoking and participation in pre-pregnancy counselling. Even a slightly raised HbA1c during early pregnancy in women with Type I diabetes carries an increased risk for fetal malformations. Therefore normoglycaemia should be strived for during early pregnancy.
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                Author and article information

                Contributors
                aleksandra.z.jotic@gmail.com
                Journal
                Diabetes Ther
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare (Cheshire )
                1869-6953
                1869-6961
                15 February 2020
                15 February 2020
                April 2020
                : 11
                : 4
                : 845-858
                Affiliations
                [1 ]GRID grid.418577.8, ISNI 0000 0000 8743 1110, Clinic for Endocrinology, Diabetes and Metabolic Diseases, , Clinical Center of Serbia, ; Dr. Subotića 13, 11000 Belgrade, Serbia
                [2 ]GRID grid.7149.b, ISNI 0000 0001 2166 9385, Faculty of Medicine, , University of Belgrade, ; Dr. Subotića 8, 11000 Belgrade, Serbia
                [3 ]GRID grid.418577.8, ISNI 0000 0000 8743 1110, Clinic for Gynecology and Obstetrics, , Clinical Center of Serbia, ; Visegradska 26, 11000 Belgrade, Serbia
                [4 ]GRID grid.7149.b, ISNI 0000 0001 2166 9385, Department for Operations Research and Statistics, Faculty of Organizational Sciences, , University of Belgrade, ; Belgrade, Serbia
                Article
                780
                10.1007/s13300-020-00780-7
                7136374
                32060738
                5543839f-e947-4cdf-9b56-f51188c82d07
                © The Author(s) 2020
                History
                : 29 December 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004564, Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja;
                Award ID: Project 175097
                Award Recipient :
                Categories
                Original Research
                Custom metadata
                © The Author(s) 2020

                Endocrinology & Diabetes
                continuous subcutaneous insulin infusion,glucose variability,pregnancy,type 1 diabetes

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