Europid Women Research Articles

Reference intervals for glycated albumin during physiological pregnancy of Europid women: Evidences from a prospective observational study

Background and AimsGlycated albumin (GA) may assess glycometabolic control over a short period of time respect to HbA1c, and its use to screen for gestational diabetes in pregnancy has been suggested. To this regard few data on reference intervals (RI) for GA on Europid women have been collected, only from cross-sectional investigations. Aim of this work has been to collect trimester-specific RI for GA in physiological pregnancies, following a longitudinal prospective study. MethodsForty-five healthy pregnant Europid women have been enrolled for whom a GDM screening test was scheduled at 24–28 weeks, in 5 different Italian centers. Only those negative to the OGTT were included. The women had 4 successive visits at 6–10 weeks of gestation, at 16–18 weeks, at 24–28 weeks and at the end of pregnancy. ALT, AST, total bilirubin, C-reactive protein, cholinesterase, creatinine, GGT, glycated albumin, iron, total serum proteins, transferrin were measured in duplicate on aliquots of serum samples by a central laboratory. ResultsThe RI (2.5–97.5 percentiles) for GA were 11.1–14.8 % (I visit), 10.9–15.6 % (II visit), 10.6–14.1 % (III visit) and 10.7–14.3 % (IV visit). The RI of other biomarkers confirmed previously published data. The RI for serum cholinesterase we present are novel, and were 5049–9906 U/L (Iv), 4212–8965 U/L (IIv), 3518–8470 U/L (IIIv) and 3945–8727 U/L (IVv). ConclusionsTrimester-specific RI are important for using GA and serum cholinesterase in pregnancy. However, considering the high inter-individual variability of both markers, the use of longitudinal interpretations of the individual variations of both proteins during pregnancy should be preferred.

Type 2 diabetes after a pregnancy with gestational diabetes among first nations women in Australia: The PANDORA study

AimsTo determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. MethodsPANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. ResultsThe cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). ConclusionsFirst Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications.

1365-P: Type 2 Diabetes after Gestational Diabetes, a High-Risk Population

Aboriginal and Torres Strait Islander women have high rates of gestational diabetes (GDM). The Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study is a prospective longitudinal cohort of women with type 2 diabetes (T2D), GDM or normoglycemia in pregnancy in the Northern Territory, Australia. In this analysis we report progression to prediabetes and T2D at 2.5 years [range 2.1, 3] postpartum in a subgroup of Aboriginal and Europid women with GDM and normoglycemia in pregnancy (n=337). Women with pre-existing T2D were excluded. Data were analysed using Fisher’s exact tests. Among Aboriginal women with GDM we assessed predictions for progression using multivariate logistic regression. Aboriginal women with GDM (n=111) were younger than Europid women with GDM (n=104) (29 years (SD 5.9) vs. 32 (5.6) p&amp;lt;0.01), with similar first trimester BMI (28.9 kg/m2 (SD 7.2) vs. 28.5 (6.7) p=0.64). Of Aboriginal women with GDM, 24 (22%) progressed to T2D and 12 (11%) to prediabetes. Of Aboriginal women with normoglycemia (n=60), 1 (2%) progressed to T2D and 1 (2%) to prediabetes (p&amp;lt;0.01 for combined outcome vs. GDM women). Of Europid women with GDM, none progressed to T2D and 4 (4%) to prediabetes and of those with normoglycemia (n=62) none progressed to diabetes or prediabetes (p=0.09 vs. GDM women). Among Aboriginal women with GDM, factors associated with postpartum diabetes or prediabetes were age (OR 1.11, 1.03-1.2) and, after adjusting for age: severity of GDM (higher fasting plasma glucose (per 1 mmol/L OR 2.11, 1.23-3.62), use of insulin (OR 3.20, 1.35-7.6)) and higher first trimester BMI (per 3 kg/m2 OR 1.22, 1.01-1.47). Not smoking was protective (OR 0.35, 0.14-0.90), although any breastfeeding at 6-months postpartum was not (OR 0.95, 0.36-2.47). To our knowledge this is the only prospective study of Aboriginal and Torres Strait Islander women with GDM. We report the highest rates in the world of T2D after GDM at 2.5 years postpartum, highlighting a need for targeted interventions in this high-risk population. Disclosure A. Wood: None. J. Boyle: None. F. Barzi: None. E.L. Barr: None. M.J.I. Hare: None. A. Titmuss: None. E. Death: None. M. Kirkwood: None. A. Simmonds: None. E.M. Moore: None. J. Oats: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. P.Z. Zimmet: None. A.D. Brown: None. J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. L.J. Maple-Brown: None.

Maternal body mass index, excess gestational weight gain, and diabetes are positively associated with neonatal adiposity in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study.

In-utero exposures likely influence the onset and severity of obesity in youth. With increasing rates of type 2 diabetes mellitus (T2DM) and maternal adiposity in pregnancy globally, it is important to assess the impact of these factors on neonatal adipose measures. To evaluate the contribution of maternal ethnicity, body mass index (BMI), gestational weight gain, and hyperglycaemia to neonatal adiposity. Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) is a longitudinal cohort study of Australian mother and neonate pairs. In this analysis, Indigenous (n=519) and Europid (n=358) women were included, of whom 644 had hyperglycaemia (type 2 diabetes [T2DM], diabetes in pregnancy [DIP], or gestational diabetes [GDM]). Associations between maternal ethnicity, hyperglycaemia, BMI and gestational weight gain, and the neonatal outcomes of length, head circumference, sum of skinfolds, total body fat, and percentage body fat were examined. Models were adjusted for maternal age, smoking status, parity, education, neonatal gender, and gestational age. Among those with hyperglycaemia in pregnancy, Indigenous women had a higher proportion of T2DM and DIP (36%, 13%) compared with Europid women (4%, 3%). In multivariate analysis, maternal T2DM (compared with no hyperglycaemia), BMI during pregnancy, and excess compared with appropriate gestational weight gain, were significantly associated with greater neonatal measures. DIP was associated with greater sum of skinfolds, total body fat, and percentage body fat. Indigenous ethnicity was associated with greater sum of skinfolds. Maternal BMI, excess gestational weight gain, and hyperglycaemia operated as independent factors influencing neonatal adiposity. Interventions addressing these factors are needed to reduce neonatal adiposity.

TUB is a candidate gene for late-onset obesity in women

We recently reported significant associations between BMI and three TUB single nucleotide polymorphisms (SNPs) in two Dutch cohorts enriched for type 2 diabetes. Here, we attempted a replication of these associations in a large population-based cohort of female twins comprehensively phenotyped for measures of general and central obesity. Two TUB SNPs (rs2272382, rs2272383) and a third (rs1528133), 22 kb distal to RIC3, were genotyped in 2694 Europid women from the St Thomas' UK Adult Twin Registry (Twins UK) (mean age +/- SD: 47.6 +/- 12.7 years; 42.8% postmenopausal). We explored the hypothesis that TUB is a candidate gene for late-onset obesity in humans through testing the interaction of the SNPs by menopausal status. In the whole cohort, none of the three SNPs showed a significant main effect on measures of general or central obesity. However, for central obesity the rs2272382 SNP showed a significant interaction with menopausal status (p = 0.036). Postmenopausal women homozygous for the minor allele of rs2272382 showed significantly more general obesity (p = 0.022) and central obesity (p = 0.009) than carriers of the major allele. Differences (beta [95% CI]) between the two genotype groups were 0.92 kg/m2 (0.03-1.81) for BMI (p = 0.036), 2.73 cm (0.62-4.84) for waist circumference (p = 0.013) and 2.43% (0.27-4.60) for per cent central fat (p = 0.027). These associations were confirmed by a sibling transmission disequilibrium test for central obesity, waist circumference and per cent central fat. We have replicated associations of TUB SNP rs2272382 with measures of general and central obesity in normal postmenopausal women. These findings confirm TUB as a candidate gene for late-onset obesity in humans.

Association of Glucocorticoid Receptor Polymorphism A3669G in Exon 9β with Reduced Central Adiposity in Women

The glucocorticoid receptor (GR) may be a common link between human obesity/metabolic syndrome and Cushing's syndrome. The effects of glucocorticoids are mediated through the functional isoform, GRalpha. An alternative isoform, GRbeta, behaves as a dominant negative inhibitor of GRalpha and has been implicated as a contributing factor to glucocorticoid resistance. A naturally occurring ATTTA to GTTTA single nucleotide polymorphism (A3669G) located in the 3' end of exon 9beta results in increased stability of GRbeta mRNA and increased GRbeta protein expression. Enhanced GRbeta expression may result in greater inhibition of GRalpha transcriptional activity, resulting in glucocorticoid insensitivity. To test the hypothesis that the 3669G allele would result in a phenotype less likely to express features of glucocorticoid excess, we studied the prevalence of this polymorphism and its relationship with obesity and features of the metabolic syndrome in 322 Europid and 262 South-Asian subjects in northeast England. We report evidence that 3669G allele is associated with reduced central obesity in Europid women and a more favorable lipid profile in Europid men. These data suggest that the 3669G allele may attenuate the undesirable effects of glucocorticoids on fat distribution and lipid metabolism, although its penetrance may vary in different ethnic groups.

Low levels of cardiovascular risk factors and coronary heart disease in a UK Chinese population.

OBJECTIVE: To compare the prevalence of cardiovascular risk factors and coronary heart disease in Chinese and Europid adults. DESIGN: Population based, cross sectional survey. SETTING: Newcastle upon Tyne, UK, 1991-93....

The 1-h 50-g Glucose Challenge Does Not Predict Large-for-Gestational-Age Infants

The relationship between the 1-h 50-g glucose challenge performed at 24-28 weeks and subsequent birth of a large-for-gestational-age infant was examined in a cohort of 368 Europid women who had no pre-existing medical condition and experienced no pregnancy complications. The results established that the 1-h 50-g glucose challenge blood glucose level had no predictive power with respect to the birth of a large-for-gestational-age infant. However, the 1-h blood glucose value was found to be significantly related to maternal height, weight and age, indicating that its level also represents processes unconnected to glucose intolerance. The study findings also re-confirmed the importance of parity, height, sex, and weight as determinants of large-for-gestational-age infants.