OBJECTIVE -The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood.RESEARCH DESIGN AND METHODS -Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995-2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data Group (NDDG) criteria. Measured weight in offspring (n ϭ 9,439) was ascertained 5-7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963-1994 standard) and then classified by maternal positive GCT (1 h Ն 7.8 mmol/l) and OGTT results (1 or Ն2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria).RESULTS -There was a positive trend for increasing childhood obesity at age 5-7 years (P Ͻ 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (Յ4,000 g). CONCLUSIONS-Our results in a multiethnic U.S. population suggest that increasing hyperglycemia in pregnancy is associated with an increased risk of childhood obesity. More research is needed to determine whether treatment of GDM may be a modifiable risk factor for childhood obesity. Diabetes Care 30:2287-2292, 2007D iabetes in pregnancy is associated with an increased rate of offspring childhood obesity, impaired glucose tolerance, and type 2 diabetes (1-7). The strongest single risk factor for obesity in Pima Indian children is exposure in utero to maternal diabetes, independent of maternal obesity and birth weight (3,4,8). Pettitt et al. (9) found an overall linear association between maternal glucose concentration (2-h glucose on the 75-g oral glucose tolerance test [OGTT]) and obesity in their offspring in Pima Indians, with the effect being most pronounced for a 2-h post-OGTT level Ն 7.8 mmol/l. Some, but not all, studies in populations other than Pima Indians reported an association of gestational diabetes mellitus (GDM) with increased obesity in offspring (7,10 -12).With normal growth, children's weight rises in proportion to height at an average age of 6 years. This period, called adiposity rebound (13)(14)(15), is thought to be a critical time of risk for adult obesity: obesity in this childhood period strongly predicts adult obesity (16 -19).We sought to determine whether increasing hyperglycemia in pregnancy, ranging from normal to GDM, is related to childhood obesity in offsp...

Objective-To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications ofnon-insulin dependent diabetes mellitus.Design-Cross sectional and longitudinal analysis of the relation between complications and concomitant results ofthe three tests.Setting-Gila River Indian Community, Arizona. Subjects-Pima Indians (cross sectional, n=960), aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination.Main outcome measures-Development of retinopathy and nephropathy.Results-Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12 0-26 7 and 3 9-4*2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12*6mmol/l; fasting plasma glucose concentration 9-3 mmol/l; glycated haemoglobin (HbAlc) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development ofretinopathy (P < 0.0001) and nephropathy (P<0.05). Receiver operating characteristic curves showed that two hour plasma glucose concentration was superior to fasting plasma glucose concentration (P< 0 05) for prevalent cases of retinopathy, but otherwise no variable had a significant advantage for detecting incident or prevalent cases ofeither complication.Conclusions-These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75 g glucose for the diagnosis ofdiabetes.

Exercise programmes designed to prevent falls in older adults also seem to prevent injuries caused by falls, including the most severe ones. Such programmes also reduce the rate of falls leading to medical care.

Obesity is one of the biggest challenges facing global reproductive health. Women in the UK and USA are today more likely to be obese or overweight at booking than normal weight, and many low-and middle-income countries (LMICs) seem destined to follow suit (Poston et al. Lancet Diabetes Endocrinol 2016;4:1025-36). Understanding how, and to what extent, maternal body mass index (BMI) and weight gain during pregnancy contribute to adverse outcomes for mothers and their offspring is therefore vital to informing future health policy.In an individual participant data meta-analysis of over 265 000 births, Santos et al. (BJOG 2019;126:984-95) confirm strong correlations between pre-pregnancy maternal BMI and the risks of gestational hypertension, preeclampsia and gestational diabetes. Over one-third of such complications in the study population were considered attributable to maternal overweight and obesity. The risk of large size for gestational age (LGA) at birth increased similarly across all categories of pre-pregnancy BMI and gestational weight gain, although these data should be interpreted in the context of a continuing debate regarding the customisation of fetal growth charts. It remains uncertain how maternal height and weight influence fetal growth potential, and whether LGA babies born to mothers who are obese or mothers with excessive weight gain carry the same short-and long-term health risks as LGA babies born to mothers who are normal weight. Preterm birth was also more common among women who are obese and past literature has suggested that this association is strongest for extremely preterm delivery (Cnattingius et al. JAMA 2013;309:2362-70), whether spontaneous or iatrogenic.Whereas women who are obese or have high weight gain are consistently shown to be at greatest risk, there is clear evidence of a continuum of risk across the full BMI range, which is emphasised by the authors' use of population attributable risk (PAR). Notably, the overall burden of pregnancy complications is similar in overweight and obese groups (PAR 11.4 and 12.5%, respectively). This calls into question traditional models of care targeting women with a booking BMI above 30 kg/m 2 or even higher thresholds. Minimising gestational weight gain in these women ameliorates but does not remove the excess risk, and ultimately may have less impact on outcomes at a population level than previously hoped.The authors acknowledge that the data were derived from cohorts who were largely white; however, comparable findings have been reported in LMICs with varied ethnic populations (Rahman et al. Obes Rev 2015;16:758-70).Being healthy entails more than just not being obese, and the study also draws important attention to the risks of small size for gestational age and preterm birth, particularly amongst underweight women with inadequate weight gain during pregnancy. These findings strengthen the argument for novel public health approaches to optimise maternal health with a shift in focus towards pre-conception and interpregnancy intervent...

BackgroundMaternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.Methods and findingsWe conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.ConclusionsIn this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large po...

Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight.Objective: Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns.Methods: We conducted a case–control study on male malformations of the genitalia nested in two French mother–child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases.Results: Adjusted birth weight decreased by 77 g [95% confidence interval (CI): –129, –25] and by 49 g (95% CI: –86, –13) in association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed concentrations were positively associated with weight (26 g; 95% CI: –2, 54) and head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in ln-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonic associations with birth weight.Conclusions: Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight.

We identified a childhood obesity locus on chromosome 6q16.3-q24.2 1 that includes 2.4 Mb common to eight genome scans for Type 2 diabetes (T2D) or obesity 1-8 . Analysis of the ENPP1 (PC-1) gene, a candidate for insulin resistance 9,10 in 6,147 subjects revealed association between a three allele risk haplotype (K121Q/IVS20 delT-11/A>G +1044 TGA, QdelTG) and childhood obesity (OR=1.69, p=0.0006), and in adults with morbid or moderate obesity (OR= 1.50, p= 0.006, OR= 1.37, p= 0.02) and also with T2D (OR=1.56, p=0.00002). The Genotype IBD Sharing Test suggested a contribution of this obesity-associated ENPP1 risk haplotype to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and to their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesityassociated A>G +1044 TGA SNP, was found to be specific for pancreatic islet beta-cells, adipocytes and liver. These findings suggest a primary role for several variants of ENPP1 in mediating insulinresistance, in the development of both obesity and type 2 diabetes, suggesting an underlying molecular mechanism common to both widespread afflictions. Competing interests statementThe authors declare that they have no competing financial interests. NIH Public Access Author ManuscriptNat Genet. Author manuscript; available in PMC 2007 October 4. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptInitially, the phenotypic characteristics of 62 "6q-evidence" families (defined by an individual pedigree Zscore > 1.0 in the 2-LOD drop interval flanked by markers D6S434 and D6S1704) were compared with the remaining 35 families from our previously published genome scan for childhood obesity 1 . The "6q-evidence" obese children have a trend towards higher area under the glycemia curve after glucose administration and a significantly lower insulinogenic index (Supplementary Table 1). Compared to none of the other families, 3.1% of the "6q-evidence" obese children are glucose intolerant or diabetic and 13.8% of 6q linked obese children parents have type 2 diabetes mellitus (T2D) compared to 3.2% of parents in other families (p=0.018). Thus, the obesity susceptibility gene(s) on chromosome 6q may be also involved in glucose homeostasis.The "6q-evidence" 2-LOD drop interval 1 covers 41.4 Mb and includes 166 referenced genes. This was narrowed to a 2.4 Mb interval between markers D6S1656 and D6S270 using overlapping published linkage results on chromosome 6q16.1-q27 with either obesity 2 , insulin secretion 3,4 or T2D 5-8 . Within this interval, the best candidate was ectonucleotide pyrophosphatase phosphodiesterase ENPP1 (also known as the Plasma Cell glycoprotein-1 PC-1). ENPP1 is believed to directly inhibit insulin-induced conformational changes of the insulin receptor, thereby affecting its activation and downstream signaling 9,11 .The microsatellite marker D6S1656 in...

Aims/hypothesis Evidence suggests that bacterial components in blood could play an early role in events leading to diabetes. To test this hypothesis, we studied the capacity of a broadly specific bacterial marker (16S rDNA) to predict the onset of diabetes and obesity in a general population. Methods Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) is a longitudinal J. Amar and M. Serino contributed equally to this study. Electronic supplementary material The online version of this article