Optimal glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes in the diabetes and pre-eclampsia intervention trial. Holmes Valerie A,Young Ian S,Patterson Christopher C,Pearson Donald W M,Walker James D,Maresh Michael J A,McCance David R, Diabetes care OBJECTIVE:To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes. RESEARCH DESIGN AND METHODS:Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA(1c) (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks' gestation (n = 592), and at 34 weeks' gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1-6.9%), moderate (7.0-7.9%), and poor (≥8.0%) glycemic control, respectively. RESULTS:Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥ 8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17-11.6]) compared with optimal control. At 26 weeks' gestation, A1C values ≥ 6.1% (good: 2.09 [1.03-4.21]; moderate: 3.20 [1.47-7.00]; and poor: 3.81 [1.30-11.1]) and at 34 weeks' gestation A1C values ≥ 7.0% (moderate: 3.27 [1.31-8.20] and poor: 8.01 [2.04-31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks' gestation, and at 34 weeks' gestation were 0.88 (0.75-1.03), 0.75 (0.64-0.88), 0.57 (0.42-0.78), and 0.47 (0.31-0.70), respectively. Glycemic control was not significantly associated with gestational hypertension. CONCLUSIONS:Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes. 10.2337/dc11-0244

Pregnancy Outcomes in Women With Diabetes-Lessons Learned From Clinical Research: The 2015 Norbert Freinkel Award Lecture. Mathiesen Elisabeth R Diabetes care Among women with diabetes, the worst pregnancy outcome is seen in the subgroup of women with diabetic nephropathy. Development of severe preeclampsia that leads to early preterm delivery is frequent. Predictors and pathophysiological mechanisms for the development of preeclampsia among women with diabetes and observational studies that support antihypertension treatment for pregnant women with microalbuminuria or diabetic nephropathy preventing preeclampsia and early preterm delivery are presented here. Obtaining and maintaining strict glycemic control before and during pregnancy is paramount to prevent preterm delivery. The cornerstones of diabetes management are appropriate diet and insulin, although the risk of severe hypoglycemia always needs to be taken into account when tailoring a diabetes treatment plan. Pathophysiological mechanisms of the increased risk of hypoglycemia during pregnancy are explored, and studies evaluating the use of insulin analogs, insulin pumps, and continuous glucose monitoring to improve pregnancy outcomes and to reduce the risk of severe hypoglycemia in pregnant women with type 1 diabetes are reported. In addition to strict glycemic control, other factors involved in fetal overgrowth are explored, and restricting maternal gestational weight gain is a promising treatment area. The optimal carbohydrate content of the diet is discussed. In summary, the lessons learned from this clinical research are that glycemic control, gestational weight gain, and antihypertension treatment all are of importance for improving pregnancy outcomes in pregnant women with preexisting diabetes. An example of how to use app technology to share the recent evidence-based clinical recommendations for women with diabetes who are pregnant or planning pregnancy is given. 10.2337/dc16-1647

Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis. Farrar Diane,Simmonds Mark,Bryant Maria,Sheldon Trevor A,Tuffnell Derek,Golder Su,Dunne Fidelma,Lawlor Debbie A BMJ (Clinical research ed.) OBJECTIVES: To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. DESIGN: Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. DATA SOURCES: Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. APPRAISAL AND DATA EXTRACTION: Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. RESULTS: 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses. CONCLUSIONS: This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013004608. 10.1136/bmj.i4694