Donald Whitelaw

Outcomes of pregnancies in women with pre-existing type 1 or type 2 diabetes, in an ethnically mixed population.

Objective  To compare the outcomes of pregnancies in women with pre‐existing, type 1 and type 2, diabetes and to examine the influence of ethnicity on these outcomes.

The importance of postpartum glucose tolerance testing after pregnancies complicated by gestational diabetes

Diabet. Med. 27, 650–654 (2010)

The Role of Maternal Gestational Diabetes in Inducing Fetal Endothelial Dysfunction

Gestational diabetes mellitus (GDM) is known to be associated with fetal endothelial dysfunction, however, the mechanisms are not fully understood. This study examines the effect of maternal diabetes on fetal endothelial function and gene expression under physiological glucose conditions (5 mM). Human umbilical vein endothelial cell (HUVEC) isolated from diabetic mothers (d.HUVEC) grew more slowly than HUVEC isolated from healthy mothers (c.HUVEC) and had delayed doubling time despite increased levels of total vascular endothelial growth factor (VEGF) expression and protein production as determined by real‐time PCR and ELISA respectively. Using western blot, the levels of antiproliferative VEGF165b isoform were increased in d.HUVEC relative to c.HUVEC. Successful VEGF165b knockdown by small interfering RNA (siRNA) resulted in increased proliferation of d.HUVEC measured by MTT, compared with negative siRNA control, to similar levels measured in c.HUVEC. In addition, d.HUVEC generated excess levels of ROS as revealed by 2′,7′ Dichlorodihydrofluorescein Diacetate (DCFH‐DA) and Nitrotetrazolium blue (NBT). Using microarray, 102 genes were differentially overexpressed between d.HUVEC versus c.HUVEC (>1.5‐fold change; P < 0.05). Functional clustering analysis of these differentially expressed genes revealed participation in inflammatory responses (including adhesion) which may be related to pathological outcomes. Of these genes, ICAM‐1 was validated as upregulated, confirming microarray results. Additional confirmatory immunofluorescence staining revealed increased protein expression of ICAM‐1 compared with c.HUVEC which was reduced by vitamin C treatment (100 μM). Thus, maternal diabetes induces persistent alterations in fetal endothelial function and gene expression following glucose normalization and antioxidant treatment could help reverse endothelium dysfunction. J. Cell. Physiol. 9999: 2695–2705, 2015.

Evaluation of the impact of universal testing for gestational diabetes mellitus on maternal and neonatal health outcomes: a retrospective analysis

BackgroundGestational diabetes (GDM) affects a substantial proportion of women in pregnancy and is associated with increased risk of adverse perinatal and long term outcomes. Treatment seems to improve perinatal outcomes, the relative effectiveness of different strategies for identifying women with GDM however is less clear.This paper describes an evaluation of the impact of a change in policy from selective risk factor based offering, to universal offering of an oral glucose tolerance test (OGTT) to identify women with GDM on maternal and neonatal outcomes.MethodsRetrospective six year analysis of 35,674 births at the Women’s and Newborn unit, Bradford Royal Infirmary, United Kingdom.ResultsThe proportion of the whole obstetric population diagnosed with GDM increased almost fourfold following universal offering of an OGTT compared to selective offering of an OGTT; Rate Ratio (RR) 3.75 (95% CI 3.28 to 4.29), the proportion identified with severe hyperglycaemia doubled following the policy change; 1.96 (1.50 to 2.58). The case detection rate however, for GDM in the whole population and severe hyperglycaemia in those with GDM reduced by 50-60%; 0.40 (0.35 to 0.46) and 0.51 (0.39 to 0.67) respectively. Universally offering an OGTT was associated with an increased induction of labour rate in the whole obstetric population and in women with GDM; 1.43 (1.35 to 1.50) and 1.21 (1.00 to1.49) respectively. Caesarean section, macrosomia and perinatal mortality rates in the whole population were similar. For women with GDM, rate of caesarean section; 0.70 (0.57 to 0.87), macrosomia; 0.22 (0.15 to 0.34) and perinatal mortality 0.12 (0.03 to 0.46) decreased following the policy change.ConclusionsUniversally offering an OGTT was associated with increased identification of women with GDM and severe hyperglycaemia and with neonatal benefits for those with GDM. There was no evidence of benefit or adverse effects in neonatal outcomes in the whole obstetric population.

Focal nail dystrophy in a cutaneous nerve distribution after trauma

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Use of continuous intravenous insulin infusion in type 1 diabetic pregnancy complicated by nephrotic syndrome

We report a case of nephrotic syndrome complicating pregnancy in a woman with CSII-treated type 1 diabetes. This was associated with deteriorating glycaemic control which was successfully managed with continuous intravenous insulin for the two weeks before delivery.

Evaluation of the impact of universal screening for gestational diabetes mellitus on maternal and neonatal health outcomes

Background Rates of gestational diabetes mellitus (GDM) are increasing. Treatment seems to reduce perinatal mortality and morbidity,1 however the impact on outcomes of alternative strategies for both screening and diagnosing GDM are unclear. The aim of this study was to evaluate the impact on health outcomes of a change from selective to universal screening. Methods Data were compared for the 3 years before and after universal screening and are presented as rate ratios (RR) for percentages of all births and births to women with GDM. Births in 2007 were excluded as they included a mixture of women who had been selectively and universally screened. Results Women diagnosed with GDM increased significantly, RR 3.78 (CI 3.31 to 4.33), as did induction of labour for all births, RR 1.43 (CI 1.35 to 1.50) and for GDM births, 1.21 (CI 1.0 to 1.49). For all births, caesarean RR was unaffected, 1 (CI 0.96 to 1.05), but reduced for GDM births, 0.7 (CI 0.57 to 0.87). Admissions to the neonatal unit decreased significantly for all births, RR 0.82 (CI 0.77 to 0.88) and GDM births, 0.43 (CI 0.32 to 0.59). RR of infants greater than 4 kg for all births was unaffected, 1.04 (CI 0.95 to 1.12), but reduced significantly for GDM births, RR 0.25 (CI 0.16 to 0.37). Conclusion Universal screening significantly increased the identification of women with GDM. Although induction of labour increased this did not lead to an increase in caesarean birth. Universal screening seemed to improve perinatal outcomes; however increased identification of those women with less severe disease may lower adverse outcome rates for GDM births.