Elisabeth Qvigstad

Assessing body composition in healthy newborn infants: reliability of dual-energy x-ray absorptiometry.

Dual-energy X-ray absorptiometry (DXA) is used to measure body composition in newborns; however, data on DXA accuracy are limited. We investigated the reliability of body composition measurements by DXA. The present study included 207 normal-term newborn babies, recruited from a larger study on the determinants of birth weight in healthy pregnancies (STORK) between 2005 and 2008. Reliability analysis of total fat mass (FM(DxA)), fat-free mass, lean mass (LM(DxA)), bone mineral content (BMC), and bone mineral density (BMD) were based on 2 DXA scans of 50 neonates. We also performed a comparison analysis for DXA (FM(DxA)) measurements and caliper (CLP) or circumference (CF) measurements of trunk and extremities (performed on all neonates, n=207). Reliability: All intraclass correlation coefficients (ICC) were satisfactory to excellent for total body and the extremity-compartment FM(DxA), LM(DxA), BMD, and BMC; ICC ranged from 0.86 to 0.96 but with a lower ICC for trunk FM(DxA). For comparison analysis, the Pearson correlation coefficients for CLP vs DXA and CF vs DXA ranged from 0.48 to 0.79 and 0.41 to 0.77, respectively. Quadriceps CLP and CF measurements correlated best with the most reliable DXA results, whereas more modest correlations were found for the trunk region. DXA measurements of body composition demonstrated good reliability and can be used as a reference method in neonates. CLP and CF measurements are appropriate for larger cohorts or when DXA is unavailable, and they provide fair rough estimations of fat mass.

Increased risk of macrosomia among overweight women with high gestational rise in fasting glucose

Objectives. Maternal overweight is a risk factor for gestational diabetes (GDM) and for newborn macrosomia. Among women without GDM, it is not well understood why some women with high body mass index (BMI) give birth to macrosomic newborns while others do not. We wanted to explore the effect of BMI and fasting plasma glucose (FPG), fasting plasma insulin (FPI) and insulin resistance (HOMA-IR) on the risk of newborn macrosomia. Methods. A cohort of 553 Caucasian women was followed throughout pregnancy. The dependent variable was high birth weight (≥4200 g). Independent variables included gestational age, intake of macronutrients and energy, maternal BMI, weight gain, FPG, FPI and HOMA-IR. Results. FPG in late pregnancy (30–32 weeks) remained a significant determinant of newborn macrosomia in multiple regression analysis (OR: 1.9, 95% CI: [1.1, 3.4]), whereas FPI and HOMA-IR did not. The women in the highest BMI quartile (≥27 kg/m2) who gave birth to macrosomic newborns had higher increase in FPG and HOMA-IR from early to late pregnancy. Among women in this BMI category, the risk for delivering a macrosomic infant was higher among those with an increase in FPG above 0.60 mmol/l (upper quartile) (OR = 4.5, 95% CI: [1.7, 12.5]). Conclusion. Fasting plasma glucose at week 30–32, but not fasting plasma insulin or insulin resistance, is a determinant of newborn macrosomia. Overweight women with high increase in fasting plasma glucose from early to late pregnancy had a 4.5-fold increase in risk of newborn macrosomia compared to the remaining group with high BMI.

Newborn Body Fat: Associations with Maternal Metabolic State and Placental Size

Background Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. Methods The present work was performed in a subcohort (n = 207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30–32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. Results Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. Conclusion Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI-related metabolic factors on fetal fat accretion to a significant extent act by modifying placental weight.

Seasonal variation in maternal and umbilical cord 25(OH) vitamin D and their associations with neonatal adiposity

DESIGN Neonatal body fat is an important indicator of foetal energy supply and growth with potential importance for long-term health. In this study, we wanted to explore seasonal variation of 25-hydroxy-vitamin D (25(OH)D) in maternal and umbilical cord plasma (UCP) to examine whether maternal and foetal 25(OH)D levels were associated with maternal BMI and neonatal fat mass (FM), and to explore the relationship among maternal and neonatal 25(OH)D levels, maternal glucose/insulin levels and UCP C-peptide. METHODS An observational, prospective study of determinants of foetal growth and birth weight in healthy pregnant women. Total body composition in 202 newborns was measured by dual-energy X-ray absorptiometry. Circulating levels of biomarkers were assessed in mothers at gestational weeks 14-16 and 30-32 and UCP. RESULTS The mean 25(OH)D concentration in UCP was significantly lower than in maternal circulation (31 vs 45 nmol/l, P<0.001). Maternal and UCP 25(OH)D levels varied significantly with season. No significant association between maternal BMI (weeks 14-16) and UCP 25(OH)D concentration was found. We found a strong positive association between maternal 25(OH)D and UCP 25(OH)D (P<0.001). There was no significant linear association between maternal BMI (weeks 14-16) and maternal 25(OH)D. We found no association between maternal 25(OH)D levels and glucose/insulin levels, nor with maternal or UCP 25(OH)D on UCP C-peptide levels. Finally, neonatal total body FM was positively associated with UCP 25(OH)D, P=0.02. CONCLUSIONS We demonstrated seasonal variation in maternal and neonatal 25(OH)D levels at northern latitudes. UCP, but not maternal, 25(OH)D was a significant predictor of neonatal total FM. Maternal BMI and metabolic parameters such as glucose, insulin and UCP C-peptide levels were not associated with 25(OH)D in mothers or offspring.

Shape information from glucose curves: Functional data analysis compared with traditional summary measures

BackgroundPlasma glucose levels are important measures in medical care and research, and are often obtained from oral glucose tolerance tests (OGTT) with repeated measurements over 2–3 hours. It is common practice to use simple summary measures of OGTT curves. However, different OGTT curves can yield similar summary measures, and information of physiological or clinical interest may be lost. Our mean aim was to extract information inherent in the shape of OGTT glucose curves, compare it with the information from simple summary measures, and explore the clinical usefulness of such information.MethodsOGTTs with five glucose measurements over two hours were recorded for 974 healthy pregnant women in their first trimester. For each woman, the five measurements were transformed into smooth OGTT glucose curves by functional data analysis (FDA), a collection of statistical methods developed specifically to analyse curve data. The essential modes of temporal variation between OGTT glucose curves were extracted by functional principal component analysis. The resultant functional principal component (FPC) scores were compared with commonly used simple summary measures: fasting and two-hour (2-h) values, area under the curve (AUC) and simple shape index (2-h minus 90-min values, or 90-min minus 60-min values). Clinical usefulness of FDA was explored by regression analyses of glucose tolerance later in pregnancy.ResultsOver 99% of the variation between individually fitted curves was expressed in the first three FPCs, interpreted physiologically as “general level” (FPC1), “time to peak” (FPC2) and “oscillations” (FPC3). FPC1 scores correlated strongly with AUC (r=0.999), but less with the other simple summary measures (−0.42≤r≤0.79). FPC2 scores gave shape information not captured by simple summary measures (−0.12≤r≤0.40). FPC2 scores, but not FPC1 nor the simple summary measures, discriminated between women who did and did not develop gestational diabetes later in pregnancy.ConclusionsFDA of OGTT glucose curves in early pregnancy extracted shape information that was not identified by commonly used simple summary measures. This information discriminated between women with and without gestational diabetes later in pregnancy.

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

OBJECTIVE To monitor beta-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy. DESIGN AND METHODS Five hundred and fifty-three pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at weeks 14-16 and 30-32. Insulin sensitivity (Matsuda index) and beta-cell function (ratio of AUC(insulin) to AUC(glucose), AUC(ins/glc)) were calculated from 520 complete tests, and subsequently beta-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (DI(o)). RESULTS Eleven women (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14-16, and 49 (9.4%) at weeks 30-32 (GDM2), which is higher than that previously reported in this region. In the subdivision of OGTT, more overweight (body mass index>25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT) 38 versus GDM2 women 58 and GDM1 women 82%, P<0.005). In early pregnancy, insulin sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. beta-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, DI(o) levels fell by 40% (P<0.001). DI(o) was significantly attenuated relative to glucose intolerance (GDM1 25% and GDM2 53%) during pregnancy. In overweight women, DI(o) levels were lower throughout pregnancy (P<0.001 versus normal weight women), this reduction was significant (P<0.01) in both NGT (21-25%) and GDM2 subjects (26-49%). CONCLUSION beta-cell function adjusted for insulin sensitivity (DI(o)) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.

MECHANISMS IN ENDOCRINOLOGY: Epigenetic modifications and gestational diabetes: a systematic review of published literature

OBJECTIVE To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research. DESIGN Systematic review. METHODS We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016. RESULTS We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring. CONCLUSION The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.

Shape information in repeated glucose curves during pregnancy provided significant physiological information for neonatal outcomes.

Objective To use multilevel functional principal component analysis to exploit the information inherent in the shape of longitudinally sampled glucose curves during pregnancy, and to analyse the impact of glucose curve characteristics on neonatal birth weight, percentage fat and cord blood C-peptide. Study Design and Setting A cohort study of healthy, pregnant women (n = 884). They underwent two oral glucose tolerance tests (gestational weeks 14–16 and 30–32), which gave two glucose curves per woman. Results Glucose values were higher, and peaked later in third trimester than in early pregnancy. The curve characteristic “general glucose level” accounted for 91% of the variation across visits, and 72% within visits. The curve characteristics “timing of postprandial peak”, and “oscillating glucose levels” accounted for a larger part of the variation within visits (15% and 8%), than across visits (7% and <2%). A late postprandial peak during pregnancy, and high general glucose levels in third trimester had significant, positive effects on birth weight (p<0.05). Generally high glucose levels during pregnancy had a significant, positive impact on neonatal percentage fat (p = 0.04). High general glucose level in third trimester had a significant, positive impact on cord blood C-peptide (p = 0.004). Conclusion Shape information in entire OGTT curves provides significant physiological information of importance for several outcomes, and may contribute to the understanding of the metabolic changes during pregnancy.

Are serum concentrations of vitamin B-12 causally related to cardiometabolic risk factors and disease? A Mendelian randomization study

Background Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality. Objectives The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2). Design We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic. Results We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol. Conclusions We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn.com/ISRCTN47414943 as ISRCTN47414943.

Prediction of Gestational Diabetes Mellitus and Pre-diabetes 5 Years Postpartum using 75 g Oral Glucose Tolerance Test at 14–16 Weeks’ Gestation

Early detection and treatment of women at risk for gestational diabetes mellitus (GDM) could improve perinatal and long-term outcomes in GDM women and their offspring. We explored if a 75 g oral glucose tolerance test (OGTT) at 14–16 weeks of gestation could identify women who will (1) develop GDM or give birth to large-for-gestational-age (LGA) babies in 1031 pregnant women from the STORK study using different diagnostic criteria (WHO1999, IADPSG2010, WHO2013, NORWAY2017) and (2) develop pre-diabetes 5 years postpartum focusing on first trimester β-cell function in a separate study of 300 women from the STORK cohort. The sensitivity of the 14–16 week OGTT to identify women who would develop GDM or have LGA babies was low, and we could not identify alternative cut-offs to exclude women not at risk or identify women that could benefit from early intervention. First trimester β-cell function was a stronger determinant than third trimester β-cell function of predicting maternal pre-diabetes. In conclusion, in our normal low-risk population, the 75 g OGTT at 14–16 weeks is insufficient to identify candidates for early treatment of GDM or identify women not likely to develop GDM or have LGA babies. First trimester β-cell function may predict pre-diabetes 5 years postpartum.