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Holmes V.A.,Queens University of Belfast | Young I.S.,Queens University of Belfast | Patterson C.C.,Queens University of Belfast | Pearson D.W.M.,Royal Infirmary | And 3 more authors.
Diabetes Care | Year: 2011

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). HbA1c (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. © 2011 by the American Diabetes Association. Source


McCance D.R.,Regional Center for Endocrinology and Diabetes
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

Despite improved obstetric surveillance and better management of maternal hyperglycaemia over the last few decades, perinatal mortality and congenital malformation rates remain several fold higher in pregnancy complicated by diabetes than in the background population. A worldwide increase in the prevalence of type 2 diabetes is now being realized in the pregnancy context with apparently similar or even worse outcomes to type 1 diabetes. While the relevance of periconceptual glycaemic control to maternal fetal outcome is clearly established, only around half of women with type 1 diabetes plan their pregnancy and rates are even lower in type 2 diabetes. In the last 5-10 years, several landmark trials have pointed to the validity of gestational diabetes mellitus as a diagnostic entity, however translation of recently published consensus guidelines for diagnosis and screening into routine clinical practice may prove challenging. An expanding therapeutic armamentarium and increasing awareness of the long-term implications of diabetic pregnancy for both mother and child present new challenges for clinical care, research and public health. © 2011 Elsevier Ltd. All rights reserved. Source


Maresh M.J.A.,University of Manchester | Holmes V.A.,Center for Public Health | Patterson C.C.,Center for Public Health | Young I.S.,Center for Public Health | And 3 more authors.
Diabetes Care | Year: 2015

RESULTS : An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks' gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9% (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3-4.8]), preeclampsia (4.3 [1.7-10.8]), need for a neonatal glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3-8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks' gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]).OBJECTIVE: To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets.RESEARCH DESIGN AND METHODS: Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks' gestationwere categorized into five groups, the lowest, <6.0% (42 mmol/mol), being the reference. Average pre-and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being the reference.CONCLUSIONS: LGA increased significantly with an A1C ‡6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ‡6.5% (48 mmol/mol). The data suggest that there is clinical utility in regularmeasurement of A1C during pregnancy. © 2015 by the American Diabetes Association. Source


McCance D.R.,Regional Center for Endocrinology and Diabetes | Holmes V.A.,Nursing and Midwifery Research Unit | Maresh M.J.A.,St Marys Hospital for Women and Children | Patterson C.C.,Center for Public Health | And 3 more authors.
The Lancet | Year: 2010

Background Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. Methods We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (α-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. Findings Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported. Interpretation Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. Source


Graham U.M.,Regional Center for Endocrinology and Diabetes | McCance D.R.,Regional Center for Endocrinology and Diabetes | Young I.S.,Queens University of Belfast | Mullan K.R.,Regional Center for Endocrinology and Diabetes
Journal of Human Hypertension | Year: 2014

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone. © 2014 Macmillan Publishers Limited. Source

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