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In the United States, the common approach to detecting gestational diabetes mellitus is the 2-step protocol recommended by the American College of Obstetricians and Gynecologists. A 50 g, 1-hour glucose challenge at 24 to 28 weeks' gestation is followed by a 100 g, 3-hour oral glucose tolerance test when a screening test threshold is exceeded. Notably, 2 or more elevated values diagnose gestational diabetes mellitus. The 2-step screening test is administered without regard to the time of the last meal, providing convenience by eliminating the requirement for fasting. However, depending upon the cutoff used and population risk factors, approximately 15% to 20% of screened women require the 100 g, 3-hour oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Groups recommends a protocol of no screening test but rather a diagnostic 75 g, 2-hour oral glucose tolerance test. One or more values above threshold diagnose gestational diabetes mellitus. The 1-step approach requires that women be fasting for the test but does not require a second visit and lasts 2 hours rather than 3. Primarily because of needing only a single elevated value, the 1-step approach identifies 18% to 20% of pregnant women as having gestational diabetes mellitus, 2 to 3 times the rate with the 2-step procedure, but lower than the current United States prediabetes rate of 24% in reproductive aged women. The resources needed for the increase in gestational diabetes mellitus are parallel to the resources needed for the increased prediabetes and diabetes in the nonpregnant population. A recent randomized controlled trial sought to assess the relative population benefits of the above 2 approaches to gestational diabetes mellitus screening and diagnosis. The investigators concluded that there was no significant difference between the 2-step screening protocol and 1-step diagnostic testing protocol in their impact on population adverse short-term pregnancy outcomes. An accompanying editorial concluded that perinatal benefits of the 1-step approach to diagnosing gestational diabetes mellitus "appear to be insufficient to justify the associated patient and healthcare costs of broadening the diagnosis." We raise several concerns about this conclusion. The investigators posited that a 20% improvement in adverse outcomes among the entire pregnancy cohort would be necessary to demonstrate an advantage to the 1-step approach and estimated the sample size based on that presumption, which we believe to be unlikely given the number of cases that would be identified. In addition, 27% of the women randomized to the 1-step protocol underwent 2-step testing; 6% of the study cohort had no testing at all. A subset of women assigned to 2-step testing did not meet the criteria for gestational diabetes mellitus but were treated as such because of elevated fasting plasma glucose levels, presumably contributing to the reduction in adverse outcomes but not to the number of gestational diabetes mellitus identified, increasing the apparent efficacy of the 2-step approach. No consideration was given to long-term benefits for mothers and offspring. All these factors may have contributed to obscuring the benefits of 1-step testing; most importantly, the study was not powered to identify what we understand to be the likely impact of 1-step testing on population health.

Objectives:To investigate associations of egg intake with blood pressure (BP) and the role of dietary variables and other macro- and micro-nutrients in the association.Design:We used cross-sectional data for the USA as part of the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). INTERMAP was surveyed between 1996 and 1999, including four 24-h dietary recalls, two 24-h urine collections and eight measurements of systolic BP and diastolic BP (SBP, DBP). Average egg intake (g/d) was calculated. Multivariable linear regression models were used to estimate the association between egg intake (per each 50 g/d or per quintile) and BP. The roles of dietary variables and other macro- and micro-nutrients in this association were also investigated.Setting:In the USA.Participants:In total, 2195 US INTERMAP men and women aged 40–59 years.Results:Participants were 50 % female, 54 % non-Hispanic White and 16 % non-Hispanic Black. Mean egg intake (sd) in men and women was 30·4(29·8) and 21·6(20·5) g/d, respectively. Adjusting for demographics, socio-economics, lifestyle and urinary Na:K excretion ratios, we found non-linear associations with BP in non-obese women (P-quadratic terms: 0·004 for SBP and 0·035 for DBP).The associations remained after adjusting for dietary variables, macro/micro nutrients or minerals. Dietary cholesterol was highly correlated with egg intake and may factor in the association. No association was found in obese women and in obese or non-obese men.Conclusion:Egg intake was non-linearly associated with SBP and DBP in non-obese women, but not in obese women or men. Underlying mechanisms require additional study regarding the role of obesity and sex.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

AIMS/HYPOTHESIS: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. METHODS: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. RESULTS: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (β = 1.388; 95% CI 0.870, 1.906; p

OBJECTIVE This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10–14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT. RESULTS Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased. CONCLUSIONS Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.

OBJECTIVE Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO Follow-up Study (FUS) included 4,160 children ages 10–14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index. RESULTS For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78–1.52) for IFG and 1.96 (1.41–2.73) for IGT. GDM was positively associated with child’s 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference −76.3 [95% CI −130.3 to −22.4] and −0.12 [−0.17 to −0.064]), respectively, but not insulinogenic index. CONCLUSIONS Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.

OBJECTIVE Excessive childhood adiposity is a risk factor for adverse metabolic health. The objective was to investigate associations of newborn body composition and cord C-peptide with childhood anthropometrics and explore whether these newborn measures mediate associations of maternal mid-pregnancy glucose and BMI with childhood adiposity. RESEARCH DESIGN AND METHODS Data on mother/offspring pairs (N=4832) from the epidemiological Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow Up Study (HAPO FUS) were analyzed. Linear regression was used to study associations between newborn and childhood anthropometrics. Structural equation modeling was used to explore newborn anthropometric measures as potential mediators of the associations of maternal BMI and glucose during pregnancy with childhood anthropometric outcomes. RESULTS In models including maternal glucose and BMI adjustments, newborn adiposity as measured by sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, p-value) BMI(0.26,0.12-0.39, CONCLUSIONS Newborn adiposity is independently associated with childhood adiposity and, along with fetal hyperinsulinemia, mediates, in part, associations of maternal glucose and BMI with childhood adiposity.

OBJECTIVE Excessive childhood adiposity is a risk factor for adverse metabolic health. The objective was to investigate associations of newborn body composition and cord C-peptide with childhood anthropometrics and explore whether these newborn measures mediate associations of maternal midpregnancy glucose and BMI with childhood adiposity. RESEARCH DESIGN AND METHODS Data on mother/offspring pairs (N = 4,832) from the epidemiological Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow-up Study (HAPO FUS) were analyzed. Linear regression was used to study associations between newborn and childhood anthropometrics. Structural equation modeling was used to explore newborn anthropometric measures as potential mediators of the associations of maternal BMI and glucose during pregnancy with childhood anthropometric outcomes. RESULTS In models including maternal glucose and BMI adjustments, newborn adiposity as measured by the sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, P value) BMI (0.26, 0.12–0.39, CONCLUSIONS Newborn adiposity is independently associated with childhood adiposity and, along with fetal hyperinsulinemia, mediates, in part, associations of maternal glucose and BMI with childhood adiposity.

BackgroundPlant-based diets are associated with a lower risk of cardiovascular diseases; however, little is known how the healthiness of the diet may be associated with blood pressure (BP). We aimed to modify three plant -based diet indices: overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) according to country-specific dietary guidelines to enable use across populations with diverse dietary patterns – and assessed their associations with BP.DesignWe used cross-sectional data including 4,680 men and women ages 40–59y in Japan, China, the United Kingdom, and the United States from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). During four visits, eight BP measurements, and four 24-h dietary recalls were collected. Multivariable regression coefficients were estimated, pooled, weighted, and adjusted extensively for lifestyle/dietary confounders.ResultsModified PDI was not associated with BP. Consumption of hPDI higher by 1SD was inversely associated with systolic (-0.82 mm Hg;95% CI:-1.32,-0.49) and diastolic BP (-0.49 mm Hg; 95% CI:-0.91, -0.28). In contrast, consumption of an uPDI was directly associated with systolic (0.77 mm Hg;95% CI:0.30,1.20). Significant associations between hPDI with BP were attenuated with separate adjustment for vegetables and whole grains; associations between uPDI and BP were attenuated after adjustment for refined grains, sugar-sweetened beverages, and meat.ConclusionAn hPDI is associated with lower BP while a uPDI is adversely related to BP. Plant-based diets rich in vegetables and whole grains and limited in refined grains, sugar-sweetened beverages, and total meat may contribute to these associations. In addition to current guidelines, the nutritional quality of consumed plant foods is as important as limiting animal-based components.Trial registration numberThe observational INTERMAP study was registered at www.clinicaltrials.gov as NCT00005271.

Context An obesogenic perinatal environment contributes to adverse offspring metabolic health. Previous studies have been limited by lack of direct adiposity measurements and failure to account for potential confounders. Objective Examine the joint associations of maternal midpregnancy body mass index (BMI) and glycemia with direct adiposity measures in 10-14 year old offspring. Design and Setting International, epidemiological study: Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and HAPO Follow-up Study, conducted between 2000-2006 and 2013-2016, respectively. Participants and Main Outcome Measures In 4832 children, adiposity measures for body mass index (BMI), body fat with air displacement plethysmography, skinfold thickness, and waist circumference were obtained at mean age 11.4 years. Results Maternal BMI and glucose, as continuous and categorical variables, were the primary predictors. In fully adjusted models controlling for child age, sex, field center, and maternal characteristics, maternal BMI had significant, positive associations with all childhood adiposity outcomes, while maternal glycemia had significant, positive associations with childhood adiposity outcomes except BMI. In joint analyses, and compared with a nonobese, nongestational diabetes mellitus (GDM) reference group, maternal obesity and GDM were associated with higher odds (maternal obesity odds ratio; OR [95% confidence interval; CI], GDM OR [95% CI]; combined OR [95% CI]) of childhood overweight/obese BMI (3.00 [2.42-3.74], 1.39 [1.14-1.71], 3.55 [2.49-5.05]), obese BMI (3.54 [2.70-4.64], 1.73 [1.29-2.30], 6.10 [4.14-8.99]), percent body fat >85th percentile (2.15 [1.68-2.75], 1.33 [1.03-1.72], 3.88 [2.72-5.55]), sum of skinfolds >85th percentile (2.35 [1.83-3.00], 1.75 [1.37-2.24], 3.66 [2.55-5.27]), and waist circumference >85th percentile (2.52 [1.99-3.21], 1.39 [1.07-1.80], 4.18 [2.93-5.96]). Conclusions Midpregnancy maternal BMI and glycemia are independently and additively associated with direct adiposity measures in 10-14 year old children. The combination of maternal obesity and GDM is associated with the highest odds of childhood adiposity.

Background Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent. Objective To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations. Methods We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40–59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers. Results No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P

Available data indicate that dietary sodium (as salt) relates directly to blood pressure (BP). Most of these findings are from studies lacking dietary data; hence, it is unclear whether this sodium–BP relationship is modulated by other dietary factors. With control for multiple nondietary factors, but not body mass index, there were direct relations to BP of 24-hour urinary sodium excretion and the urinary sodium/potassium ratio among 4680 men and women 40 to 59 years of age (17 population samples in China, Japan, United Kingdom, and United States) in the INTERMAP (International Study on Macro/Micronutrients and Blood Pressure), and among its 2195 American participants, for example, 2 SD higher 24-hour urinary sodium excretion (118.7 mmol) associated with systolic BP 3.7 mm Hg higher. These sodium–BP relations persisted with control for 13 macronutrients, 12 vitamins, 7 minerals, and 18 amino acids, for both sex, older and younger, blacks, Hispanics, whites, and socioeconomic strata. With control for body mass index, sodium–BP—but not sodium/potassium–BP—relations were attenuated. Normal weight and obese participants manifested significant positive relations to BP of urinary sodium; relations were weaker for overweight people. At lower but not higher levels of 24-hour sodium excretion, potassium intake blunted the sodium–BP relation. The adverse association of dietary sodium with BP is minimally attenuated by other dietary constituents; these findings underscore the importance of reducing salt intake for the prevention and control of prehypertension and hypertension. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005271.

BACKGROUND: Several studies have reported that dietary salt intake may be an independent risk factor for overweight/obesity, but results from previous studies are controversial, reflecting study limitations such as use of a single spot urine or dietary recall to estimate daily salt intake rather than 24-h urine collections, and population samples from only a single country or center. OBJECTIVE: The aim of this study was to use data from the International Study of Macro-/Micro-nutrients and Blood Pressure (INTERMAP Study) to explore the relation between dietary salt intake estimated from 2 timed 24-h urine collections and body mass index (BMI; in kg/m(2)) as well as prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States. METHODS: Data were from a cross-sectional study of 4680 men and women aged 40–59 y in Japan (n = 1145), China (n = 839), the United Kingdom (n = 501), and the United States (n = 2195). General linear models were used to obtain the regression coefficients (β) of salt intake associated with BMI. Multivariable logistic regression models were used to determine the ORs and 95% CIs of overweight/obesity associated with a 1-g/d higher dietary salt intake. RESULTS: After adjustment for potential confounding factors including energy intake, salt intake 1 g/d higher was associated with BMI higher by 0.28 in Japan, 0.10 in China, 0.42 in the United Kingdom, and 0.52 in the United States, all P values

The Na/K ratio may be more strongly related to blood pressure and cardiovascular disease than sodium or potassium. The casual urine Na/K ratio can provide prompt on-site feedback, and with repeated measurements, may provide useful individual estimates of the 24-h ratio. The World Health Organization has published guidelines for sodium and potassium intake, but no generally accepted guideline prevails for the Na/K ratio. We used standardized data on 24 h and casual urinary electrolyte excretion obtained from the INTERSALT Study for 10,065 individuals aged 20–59 years from 32 countries (52 populations). Associations between the casual urinary Na/K ratio and the 24-h sodium and potassium excretion of individuals were assessed by correlation and stratification analyses. The mean 24-h sodium and potassium excretions were 156.0 mmol/24 h and 55.2 mmol/24 h, respectively; the mean 24-h urinary Na/K molar ratio was 3.24. Pearson’s correlation coefficients (r) for the casual urinary Na/K ratio with 24-h sodium and potassium excretions were 0.42 and −0.34, respectively, and these were 0.57 and −0.48 for the 24-h ratio. The urinary Na/K ratio predicted a 24-h urine Na excretion of

Background: Magnesium (Mg) and other mineral intakes are vital contributors to a healthy diet and appear to have a modest effect on the risk of hypertension. Studies suggest that supplemental Mg can significantly lower blood pressure (BP). Here, we investigate associations of total Mg consumption with the level of its urinary metabolomic biomarkers, and BP. Method: We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) on 4269 men and women aged 40-59 years from Japan, China, United Kingdom, and United States (US). Regression coefficients with BP per 2 standard deviation (SD) higher dietary Mg from food plus supplement (obtained from 24-hr dietary recalls), urinary Mg (measured by atomic absorption flame photometry) and small molecules (analysed by direct injection mass spectrometry) were estimated using multivariable models, adjusted for age, gender, population sample, intake of total energy and other confounders (see Table). To estimate overall association, country-specific regression coefficients were pooled, weighted by inverse of their variance. Results: Average Mg intakes were 454 (SD=207) mg/day for 770 persons who reported Mg supplementation (89% from US), and 300 (SD=101) mg/day for those who did not. High correlation was found between Mg intake from food plus supplements with urinary Mg ( r =0.38, PP =6x10 -5 ). Urinary Mg excretion higher by 2.66 mmol/day was associated with a diastolic BP difference of -1.02 mm Hg (P=0.02). There was a non-significant inversed association between ascorbic acid and BP in some multivariable regression models. Conclusion: Higher intake of Mg, including supplements, was associated with lower BP levels.

Background: Evidence relating to the benefit of fish consumption on blood pressure (BP) management is inconclusive. Recent research has suggested that different patterns in fish consumption across geographic regions may modify the association between fish intake and cardiovascular outcomes. Objectives: To investigate the associations between fish intake and BP in Asian and Western population groups and to explore the associations between candidate urinary biomarkers of fish intake and BP. Methods: The International Study on Macro/Micronutrients and Blood Pressure (INTERMAP) surveyed 4680 men and women aged 40-59 years from four countries: United States of America (US), United Kingdom (UK), Peoples Republic of China (PRC) and Japan between 1996 and 1999. Standardized quality-controlled measures collected included: four 24-hour dietary recalls and two 24-hour urine collections and eight BP measurements. Proton nuclear magnetic resonance spectra of urine specimens were acquired, and partial correlation analysis adjusted for age, sex, and sample/centre were performed to identify candidate peak variables correlating to total fish and shellfish intakes. Multivariable linear regression models conducted on pooled data by geographic region (Asian: Japan and PRC; n = 1984, and Western: UK and US; n = 2696) estimated differences in BP per 2SD (33.4g/1000kcal) of total fish intake and identified urinary metabolites. Results: Japan reported the highest daily intake of fish (mean 40.3, SD 22.3 g/1000kcal) with 99% of the cohort classified as consuming fish. Mean daily fish consumption patterns were comparable between the US (9.0 SD 15.0 g/1000kcal; 53% consumers) and UK (8.5 SD, 12.4 g/1000kcal; 55% consumers). No associations were observed between total fish intake and BP in individual cohorts or by geographic region. Trimethylamine N-oxide (TMAO), taurine and homarine were identified as candidate urinary biomarkers of fish intake. Homarine showed a strong correlation with shellfish intake ( r =0.43, P β 0.32 95%CI 0.14, 0.50, P = 0.0006; fully adjusted for lifestyle and dietary intakes), this remained significant following adjustment for body mass index ( β 0.23, 95%CI 0.05, 0.41, P = 0.012). Taurine and homarine were not associated with BP. Conclusion: We observed no association between fish consumption and BP across Asian or Western populations. The differential association between urinary TMAO and DBP in Western and Asian population groups requires further investigation.

OBJECTIVE To assess the frequency of adverse outcomes for women who are diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. RESEARCH DESIGN AND METHODS This is a secondary analysis from the North American HAPO study centers. Glucose measurements from a 75-g oral glucose tolerance test were used to group participants into three nonoverlapping categories: GDM based on Carpenter-Coustan (CC) criteria (also GDM based on IADPSG criteria), GDM diagnosed based on IADPSG criteria but not CC criteria, and no GDM. Newborn outcomes included birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile; maternal outcomes included primary cesarean delivery and preeclampsia. Outcome frequencies were compared using multiple logistic regression, adjusting for predefined covariates. RESULTS Among 25,505 HAPO study participants, 6,159 blinded participants from North American centers were included. Of these, 81% had normal glucose testing, 4.2% had GDM based on CC criteria, and 14.3% had GDM based on IADPSG criteria but not CC criteria. Compared with women with no GDM, those diagnosed with GDM based on IADPSG criteria had adjusted odds ratios (95% CIs) for birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile, as well as primary cesarean delivery and preeclampsia, of 1.87 (1.50–2.34), 2.00 (1.54–2.58), 1.73 (1.35–2.23), 1.31 (1.07–1.60), and 1.73 (1.32–2.27), respectively. CONCLUSIONS Women diagnosed with GDM based on IADPSG criteria had higher adverse outcome frequencies compared with women with no GDM. These data underscore the need for research to assess the effect of treatment to improve outcomes in such women.

Introduction The preschool years provide a unique window of opportunity to intervene on obesity-related lifestyle risk factors during the formative years of a child's life. The purpose of this study was to assess the impact of a preschool-based obesity prevention effectiveness trial at 1-year follow-up. Design RCT. Settings/participants Primarily African American children (aged 3–5 years, N=618) attending Head Start preschool programs administered by Chicago Public Schools. Methods Eighteen preschools were randomly assigned in 2007–2008 to receive either (1) a 14-week teacher-delivered intervention focused on healthy lifestyle behaviors or (2) a 14-week teacher-delivered general health curriculum (control group). Main outcome measures The primary outcome, BMI, was measured at baseline, postintervention, and 1-year follow-up. Diet and screen time behaviors were also assessed at these time points. Multilevel mixed effects models were used to test for between-group differences. Data were analyzed in 2014. Results Significant between-group differences were observed in diet, but not in BMI z-score or screen time at 1-year follow-up. Diet differences favored the intervention arm over controls in overall diet quality ( p =0.02) and in subcomponents of diet quality, as measured by the Healthy Eating Index-2005, and in fruit intake (servings/day, excludes juice) ( p =0.02). Diet quality worsened more among controls than the intervention group at 1-year follow-up. Conclusions The adaptation of Hip-Hop to Health Jr. produced modest benefits in diet quality but did not significantly impact weight gain trajectory. Not unlike other effectiveness trials, this real-world version delivered by Head Start teachers produced fewer benefits than the more rigorous efficacy trial. It is important to understand and build upon the lessons learned from these types of trials so that we can design, implement, and disseminate successful evidence-based programs more widely and effectively. Trial registration This study is registered at www.clinicaltrials.gov NCT00241878.

Importance The sequelae of gestational diabetes (GD) by contemporary criteria that diagnose approximately twice as many women as previously used criteria are unclear. Objective To examine associations of GD with maternal glucose metabolism and childhood adiposity 10 to 14 years’ postpartum. Design, Setting, and Participants The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study established associations of glucose levels during pregnancy with perinatal outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers and 4832 children; study visits occurred between February 13, 2013, and December 13, 2016). Exposures Gestational diabetes was defined post hoc using criteria from the International Association of Diabetes and Pregnancy Study Groups consisting of 1 or more of the following 75-g oral glucose tolerance test results (fasting plasma glucose ≥92 mg/dL; 1-hour plasma glucose level ≥180 mg/dL; 2-hour plasma glucose level ≥153 mg/dL). Main Outcomes and Measures Primary maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes or prediabetes). Primary outcome for children: being overweight or obese; secondary outcomes: obesity, body fat percentage, waist circumference, and sum of skinfolds (>85th percentile for latter 3 outcomes). Results The analytic cohort included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was 11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall and by 14.1% (683/4832) of mothers of participating children. Among mothers with GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1% (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14]; risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers without GD. Adjusted for maternal body mass index during pregnancy, the OR was 1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD was 3.7% (95% CI, −0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was 1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI, 0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to 1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%). Conclusions and Relevance Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.

OBJECTIVE: The present study aims to compare 24-h dietary recalls with 24-h urine collections for the estimation of sodium intake at both population and individual levels in China, Japan, the United Kingdom (UK), and the United States of America (USA), using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). METHODS: Mean differences between 24-h dietary recalls and 24-h urine collections were calculated for their agreement in estimating sodium intake at the population level; relative and absolute differences as well as misclassification of salt intake groups (salt intake

Background: Urinary sodium-to-potassium ratio may be more strongly related to blood pressure and cardiovascular disease than either urinary sodium or potassium alone. The casual urine sodium-to-potassium ratio is readily obtained, can provide prompt on-site feedback, and with repeated measurements may provide useful individual estimates of 24-hour urinary sodium-to-potassium ratio. The World Health Organization (WHO) has recently published guidelines for sodium and potassium intakes, but no generally accepted guideline prevails for favorable sodium-to-potassium ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERSALT is an international study on associations of multiple urinary variables, with blood pressure (BP), based on standardized data on 24-hour and casual urinary electrolyte excretion in 10,065 individuals from 52 population samples in 32 countries. The associations between casual urinary sodium-to-potassium ratio and 24-hour urinary sodium and potassium excretion of individuals were assessed by correlation and stratification analysis. Results: Mean 24-hour sodium and potassium excretions were 156.0 mmol/24h and 55.2 mmol/24h; mean 24-hour urinary sodium-to-potassium ratio was 3.24. Pearson-r correlation coefficients of casual urinary sodium-to-potassium ratio with 24-hour sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for 24-hour urinary sodium-to-potassium ratio. The proportion of participants with estimated sodium chloride intake below the WHO recommended guideline of 85 mmol/day was 61.1% for those with casual urinary sodium-to-potassium ratio less than 1, and 96.3% where the 24-hour ratio was less than 1. For potassium, the proportion of people with potassium intake more than the WHO recommended guideline of 90 mmol/day was 21.3% where the casual urinary sodium-to-potassium ratio was less than 1 and 28.6% for the 24-hour urinary sodium-to-potassium ratio. Conclusions: Casual urinary sodium-to-potassium ratio less than 1 may be a useful indicator of adherence to the World Health Organization recommended levels of sodium intake, and to a lesser extent potassium intake in diverse different populations.

Objective. An association between 25-hydroxyvitamin D (25[ OH] D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH) D levels with CV risk factors and to determine whether low baseline 25(OH) D levels predict future CV events in patients participating in an international inception cohort. Methods. Data were collected on 890 participants, including demographics, SLE activity and damage assessments, CV risk factors and events, medications, laboratory assessments of 25(OH) D levels, and inflammatory markers. Multiple logistic and Cox regressions were used to estimate the associations of baseline 25(OH) D levels with baseline CV risk factors and CVD events. The models were adjusted for age, sex, race, season, and country, with and without body mass index. Results. Patients in the higher quartiles of 25(OH) D were less likely to have hypertension and hyperlipidemia and were more likely to have lower C-reactive protein levels and lower Systemic Lupus Erythematosus Disease Activity Index 2000 scores at baseline when compared with the first quartile. Vitamin D levels were not independently associated with CVD event incidence; however, hazard ratios for CVD event incidence decreased with successively higher quartiles. Conclusion. Lower baseline 25(OH) D levels are associated with higher risk for CV risk factors and more active SLE at baseline. There may be a trend toward a lower likelihood of CVD events in those with higher baseline 25(OH) D levels. (Less)

Patients with SLE have an increased risk of cardiovascular disease at a much earlier age than the general population1. SLE itself has been shown to be an independent risk factor in the progression of atherosclerosis2. The associated morbidity and mortality of cardiovascular disease has prompted the study of subclinical atherosclerosis in the SLE population, as measured with imaging studies such as carotid ultrasound and electron beam computed tomography (CT) scans3. Higher aorta calcium scores (AC) and coronary artery calcification (CAC) have been shown to be more prevalent in SLE patients when compared with age- and sex-matched controls4. CAC has also been shown to occur at a younger age in the SLE population4,5 when compared with controls. Similarly, SLE patients appear to have an accelerated rate of atherosclerosis progression when compared with the general population, however the mechanisms or manner underlying this is not clear. Older age and longer disease duration were associated with carotid plaque progression in an early study6, and in another, after controlling for age, traditional factors including higher LDL levels and current smoking status, as well as SLE-related factors, including higher serum C3 level and higher Systemic Lupus Activity Measure (SLAM) score, were associated with carotid plaque progression7. Carotid intima media thickness (IMT) progression has been associated also with higher serum creatinine, homocysteine level, and C3 level7,8. Kiani et al further investigated cumulative exposure to risk factors in progression of IMT, carotid plaque, and CAC9. In their multivariate analyses, progression in CAC was associated with age, current smoking, and lower high-sensitivity C-reactive protein (hsCRP), but not with SLE disease activity measures. There are very few studies that have investigated risk factors in the progression of CAC and none that have explored risk factors for AC progression in those with SLE. We investigated baseline traditional and SLE-related risk factors in the progression of CAC and AC in women with SLE and in comparison with a control population. We hypothesized that not only would the rate of progression in CAC and AC be greater in those with SLE when compared with controls, but also that the risk factors for progression would differ between the groups. This is the first study to explore progression in AC in women with SLE.

To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds90th percentile (OR = 1.75 and 4.77, respectively) and percentage body fat90th percentile (OR = 2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight90th percentile (OR = 2.80 and 1.93, respectively) compared to women who gained within the recommendation.This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.

ObjectiveThis study aimed to collect data to compare blood pressure values between random-zero sphygmomanometers and automated oscillometric devices and generate equations to convert blood pressure values from one device to the other.MethodsOmron HEM-907, a widely used automated oscillometric device in many epidemiologic surveys and cohort studies, was compared here with random-zero sphygmomanometers. Two hundred and one participants aged 40-79 years (37% men) were enrolled and randomly assigned to one of two groups with blood pressure measurement first taken by automated oscillometric devices or by random-zero sphygmomanometers. The study design enabled comparisons of blood pressure values between random-zero sphygmomanometers and two modes of this automated oscillometric device – automated and manual, and assessment of effects of measurement order on blood pressure values.ResultsAmong all participants, mean blood pressure levels were lowest when measured with random-zero sphygmomanometers compared with both modes of automated oscillometric devices. Several variables, including age and gender, were found to contribute to the blood pressure differences between random-zero sphygmomanometers and automated oscillometric devices. Equations were developed using multiple linear regression after taking those variables into account to convert blood pressure values by random-zero sphygmomanometers to automated oscillometric devices.ConclusionEquations developed in this study could be used to compare blood pressure values between epidemiologic and clinical studies or identify shift of blood pressure distribution over time using different devices for blood pressure measurements.

The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic process and criteria for gestational diabetes mellitus (GDM) have been recommended by the World Health Organization for adoption and were widely introduced into clinical practice in Australia from January 2015 - in Queensland, the Australian Capital Territory and variably across other states. The IADPSG criteria identify women at increased risk of a range of adverse pregnancy outcomes related to maternal hyperglycaemia. The relationship between maternal hyperglycaemia and adverse outcomes is continuous; however, one elevated glucose value is sufficient to impart a higher risk of pregnancy complications. We outline the background and statistical foundations of the IADPSG approach and refute the inference that invalid statistical reasoning underlies the IADPSG approach. The prevalence of GDM diagnosed by IADPSG criteria may be higher or lower than with other criteria, depending on the underlying population prevalence of fasting and post-glucose load hyperglycaemia, which in turn vary with ethnicity. Studies comparing previous Australian criteria to the IADPSG criteria suggest GDM prevalence may decrease or may increase by up to 35% in specific populations with the planned change in criteria. Pregnancy complications have multiple potential underlying causes. No set of glucose criteria will ever be able to fully separate women and babies at risk of pregnancy complications from those who are not.

OBJECTIVE To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS We compared fasting serum from an oral glucose tolerance test at ∼28 weeks’ gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (>90th percentile) FPG with 50 mothers with low ( RESULTS High-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]-adjusted P < 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P < 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P < 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative association between maternal glycine and cord C-peptide (P < 0.05). CONCLUSIONS Metabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 μg/l higher for TT higher by 1 SD, p = 0.001) and 1-h C-peptide (0.79 μg/l higher for TT higher by 1 SD, p < 0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 μg/l higher for FT higher by 1 SD, p < 0.001), and 1-h C-peptide (0.83 μg/l higher for FT higher by 1 SD, p < 0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity.

Objectives This study sought to estimate lifetime risk for heart failure (HF) by sex and race. Background Prior estimates of lifetime risk for developing HF range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made. Methods Using public-release and internal datasets from National Heart, Lung, and Blood Institute–sponsored cohorts, we estimated lifetime risks for developing HF to age 95 years, with death free of HF as the competing event, among participants in the CHA (Chicago Heart Association Detection Project in Industry), ARIC (Atherosclerosis Risk in Communities), and CHS (Cardiovascular Health Study) cohorts. Results There were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30% to 42% in white men, 20% to 29% in black men, 32% to 39% in white women, and 24% to 46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher blood pressure and body mass index at all ages in both blacks and whites, and did not diminish substantially with advancing index age. Conclusions These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.

Background Association between casual and 24-h urinary sodium-to-potassium (Na/K) ratio is well recognized, although it has not been validated in diverse demographic groups. Our aim was to assess utility across and within populations of casual urine to estimate 24-h urinary Na/K ratio using data from the INTERSALT Study. Methods The INTERSALT Study collected cross-sectional standardized data on casual urinary sodium and potassium and also on timed 24-h urinary sodium and potassium for 10 065 individuals from 52 population samples in 32 countries (1985–87). Pearson correlation coefficients and agreement were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio both at population and individual levels. Results Pearson correlation coefficients relating means of 24-h urine and casual urine Na/K ratio were r = 0.96 and r = 0.69 in analyses across populations and individuals, respectively. Correlations of casual urine Na/creatinine and K/creatinine ratios with 24-h urinary Na and K excretion, respectively, were lower than correlation of casual and 24-h urinary Na/K ratio in analyses across populations and individuals. The bias estimate with the Bland–Altman method, defined as the difference between Na/K ratio of 24-h urine and casual urine, was approximately 0.4 across both populations and individuals. Spread around, the mean bias was higher for individuals than populations. Conclusion With appropriate bias correction, casual urine Na/K ratio may be a useful, low-burden alternative method to 24-h urine for estimation of population urinary Na/K ratio. It may also be applicable for assessment of the urinary Na/K ratio of individuals, with use of repeated measurements to reduce measurement error and increase precision.

Background: High dietary sodium (Na), low dietary potassium (K) and high dietary sodium/potassium (Na/K) ratio are associated with adverse blood pressure levels and excess risks of cardiovascular diseases. 24-h urine collection is the gold standard for measuring dietary Na, K and Na/K ratio. Recommended levels of Na and K intakes are suggested in WHO guidelines; less than 85 mmol/day for Na; at least 90 mmol/day for K; there is no definitive guideline for Na/K ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERMAP is an international study on associations of multiple dietary variables with blood pressure (BP), based on two timed 24-hr urine collections and dietary data from 4 in-depth 24-h dietary recalls in 4,680 men and women ages 40-59 years in China, Japan, United Kingdom and United States (US). Na/K ratio of 24-hr urine stratified in 1 unit intervals was compared with the current recommended levels of Na and K intakes suggested in WHO guidelines. Na intake was evaluated by urinary Na excretion; K intake by dietary K intake. Results: Thirty-one of the 4,680 INTERMAP participants (0.7%) had urinary Na/K ratio less than 1. The proportions of participants with Na excretion less than 2 g/day (85 mmol/day) among all 4,680 individuals were 77% (n=24), 19% (n=117), and 0.2% (n=11) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples (n=2,195) the proportions were 88% (n=15), 19% (n=70), and 0.3% (n=6), respectively. The proportions of participants with dietary K intake more than 3.51 g/day (90 mmol/day) among all 4,680 individuals were 71% (n=22), 38% (n=233), and 2.4% (n=111) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples the proportions were 59% (n=10), 38% (n=138), and 2.1% (n=47), respectively. Conclusions: WHO recommends Na intake less than 85 mmol/day, and K intake more than 90 mmol/day. Urinary Na/K ratio less than 1 is needed to ensure reasonable compliance with these recommendations. Currently, very few people satisfy urinary Na/K ratio less than 1, so population-wide efforts are needed to reduce salt (sodium chloride) and increase K intake.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study showed significant perinatal risks at levels of maternal hyperglycemia below values that are diagnostic for diabetes. A Consensus Panel of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) reviewed HAPO Study results and other work that examined associations of maternal glycemia with perinatal and long-term outcomes in offspring and published recommendations for diagnosis and classification of hyperglycemia in pregnancy in 2010. Subsequently, some commentaries and debate challenged the IADPSG recommendations. In this review, we provide details regarding some points that were considered by the IADPSG Consensus Panel but not published and address the following issues: 1) what should be the frequency of gestational diabetes mellitus (GDM); 2) were appropriate outcomes and odds ratios used to define diagnostic thresholds for GDM; 3) to improve perinatal outcome, should the focus be on GDM, obesity, or both; 4) should results of randomized controlled trials of treatment of mild GDM influence recommendations for diagnostic thresholds; and, 5) other issues related to diagnosis of GDM. Other groups are independently considering strategies for the diagnosis of GDM. However, after careful consideration of these issues, we affirm our support for the recommendations of the IADPSG Consensus Panel.

Background: Clinical trial data show that reduction in total energy intake enhances weight loss regardless of the macronutrient composition of the diet. Few studies have documented dietary patterns or nutrient intakes that favor leanness [BMI (in kg/m2) ≤25] in free-living populations. Objective: This investigation examined associations of usual energy, food, and nutrient intakes with BMI among US participants of the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). Design: The INTERMAP is an international cross-sectional study of dietary factors and blood pressure in men and women (ages 40–59 y) that includes 8 US population samples. The present study included data from 1794 Americans who were not consuming a special diet and who provided four 24-h dietary recalls and 2 timed 24-h urine collections. Multivariable linear regression with the residual method was used to adjust for energy intake; sex-specific associations were assessed for dietary intakes and urinary excretions with BMI adjusted for potential confounders including physical activity. Results: Lower energy intake was associated with lower BMI in both sexes. Univariately, higher intakes of fresh fruit, pasta, and rice and lower intakes of meat were associated with lower BMI; these associations were attenuated in multivariable analyses. Lower urinary sodium and intakes of total and animal protein, dietary cholesterol, saturated fats, and heme iron and higher urinary potassium and intakes of carbohydrates, dietary fiber, and magnesium were associated with lower BMI in both sexes. Conclusion: The consumption of foods higher in nutrient-dense carbohydrate and lower in animal protein and saturated fat is associated with lower total energy intakes, more favorable micronutrient intakes, and lower BMI.

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

OBJECTIVE To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. RESEARCH DESIGN AND METHODS Eligible pregnant women underwent a 75-g OGTT at 24–32 weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. RESULTS Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. CONCLUSIONS On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.

Individuals with favorable levels of readily measured cardiovascular disease (CVD) risk factors (low risk, LR) experience low long-term rates of CVD mortality and greater longevity. The purpose of the current study was to compare nutrient/food intakes of LR participants with participants not LR in the INTERMAP study.Men and women (40-59 years) from 17 population samples in four countries (China, Japan, UK, US) provided four 24-h dietary recalls and two timed 24-h urine collections. LR was defined as meeting all of the following CVD risk criteria: systolic/diastolic blood pressure (BP) ≤ 120/ ≤ 80 mmHg; no drug treatment for high BP, hyperlipidemia, or CVD; non-smoking; BMI25.0 kg/m(2) (US, UK) or23.0 kg/m(2) (China, Japan); alcohol consumption26.0 g/day (men)/13.0 g/day (women); and no history of diabetes or CVD. Multivariate logistic regression was used to examine associations of nutrient/food intakes with LR.LR individuals reported higher intake of vegetable protein, fiber, magnesium, non-heme iron, potassium; lower energy intake; lower intake of cholesterol, saturated fatty acids, animal protein; and lower 24-h urinary sodium compared with individuals not LR. With regard to foods, LR individuals reported higher intake of fruits, vegetables, grains, pasta/rice, fish; lower intakes of meats, processed meats, high-fat dairy, and sugar-sweetened beverages than individuals not LR.Lower energy intake and differential intake of multiple specific nutrients and foods are characteristic of individuals at low risk for developing CVD. Identification of dietary habits associated with LR is important for further development of public health efforts aimed at reduction/prevention of CVD.

Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40–59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20–59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels.

OBJECTIVE: A direct relationship of dietary cholesterol to blood pressure of men has been reported in a few observational studies from the USA. It is not clear whether this association prevails consistently, for example, in populations with varied dietary habits, across ethnic groups, and sexes. Cross-sectional data from the International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP) were used to assess relations of dietary cholesterol intake to blood pressure in men and women from four countries. METHODS: Data include 83 nutrients from four multipass 24-h dietary recalls and two-timed 24-h urine collections; eight blood pressure readings, and questionnaire data, for 4680 participants ages 40-59 years from 17 population samples in Japan, People's Republic of China, UK, and USA. RESULTS: With sequential models to control for multiple possible confounders (dietary, other), linear regression analyses showed that dietary cholesterol was directly related to SBP for all participants and for nonhypertensive individuals, but not to DBP. With adjustment for 12 variables, estimated SBP differences with 2SD for higher cholesterol intake (131.0 mg/1000 kcal) were 0.9 mmHg (P < 0.05) for all participants and 1.1 mmHg (P < 0.01) for nonhypertensive individuals, findings attenuated with addition of height and weight to the model. CONCLUSION: INTERMAP found a low-order, positive relationship of dietary cholesterol intake to SBP with control for multiple possible confounders. Reduction of dietary cholesterol intake may contribute to prevention and control of adverse blood pressure levels in general populations. J Hypertens

OBJECTIVE: The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity. METHODS: A total of 17 094 mothers and infants were included in the Hyperglycemia and Adverse Pregnancy Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and neonatal blood samples were collected. Biochemical neonatal hypoglycemia was defined as glucose levels of RESULTS: Plasma glucose concentrations were stable during the first 5 hours after birth. Maternal glucose levels were weakly positively associated with biochemical neonatal hypoglycemia (odds ratios: 1.07–1.14 for 1-SD higher OGTT glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C-peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category). Larger and/or fatter infants were more likely to have hypoglycemia (P < .001), and infants with hypoglycemia tended to have a higher frequency of cord C-peptide levels of >90th percentile. CONCLUSIONS: Mean neonatal plasma glucose concentrations varied little in the first 5 hours after birth, which suggests normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly related to maternal OGTT glucose measurements but were strongly associated with elevated cord serum C-peptide levels. Larger and/or fatter infants were more likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest physiologic relationships between maternal glycemia and fetal insulin production.

OBJECTIVE Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy. RESEARCH DESIGN AND METHODS We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24–32 weeks' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics. RESULTS The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P < 0.0001), 1-h glucose in Europeans (P = 0.001), and 2-h glucose in Thais (P = 0.005). It was also associated with higher European offspring birth weight, fat mass, and skinfold thicknesses (P < 0.05). The TCF7L2 variant was associated with all three maternal glucose outcomes (P = 0.03, P < 0.0001, and P < 0.0001 for fasting and 1-h and 2-h glucose, respectively) in the Europeans but not in the Thais (P > 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001–0.08). CONCLUSIONS Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants.

Racial differences exist in disease rates and mortality in both cardiovascular disease (CVD) and systemic lupus erythematosus (SLE). The objective of this cross-sectional study was to compare the frequency and risk factors for subclinical CVD in African American (AA) and Caucasian women with SLE and no prior CVD events. Traditional CVD risk factors and SLE-related factors were assessed in 309 SLE women. Subclinical CVD was assessed by carotid ultrasound to measure intimamedial thickness (IMT) and plaque, and electron beam computed tomography (EBCT) was used to measure coronary artery calcium (CAC). AA women had less education and higher levels of body mass index, blood pressure, lipoprotein(a), C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR). However, AA women had lower albumin, more and longer duration of corticosteroid use, higher SLE disease activity and damage, and more dsDNA antibodies compared with Caucasian women after adjustment for age and study site. More AA women had carotid plaque (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.03–3.65) and higher carotid IMT (0.620 vs 0.605 mm, P = 0.07) but similar CAC compared with Caucasians. A multivariate analysis revealed that the following risk factor variables were significantly different between the racial groups and associated with plaque: blood pressure, current corticosteroid use, SLE disease activity, and SLE damage. All factors contributed to the result, but no individual risk factor fully accounted for the association between race and plaque. In conclusion, the presence of carotid plaque was higher in AA compared with Caucasian women with SLE, in contrast to studies of non-SLE subjects, in which AA have similar or less plaque than Caucasians. A combination of SLE-related and traditional CVD risk factors explained the racial difference in plaque burden.

Raised blood pressure is a leading cause of morbidity and mortality worldwide; improved nutritional approaches to population-wide prevention are required. Few data are available on dietary phosphorus and blood pressure and none are available on possible combined effects of phosphorus, magnesium, and calcium on blood pressure. The International Study of Macro- and Micro-Nutrients and Blood Pressure is a cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population samples in Japan, China, United Kingdom, and United States. Blood pressure was measured 8 times at 4 visits. Dietary intakes were obtained from four 24-hour recalls plus data on supplement use. Dietary phosphorus was inversely associated with blood pressure in a series of predefined multiple regression models, with the successive addition of potential confounders, both nondietary and dietary. Estimated blood pressure differences per 232 mg/1000 kcal (2 SD) of higher dietary phosphorus were −1.1 to −2.3 mm Hg systolic/−0.6 to −1.5 mm Hg diastolic (n=4680) and −1.6 to −3.5 mm Hg systolic/−0.8 to −1.8 mm Hg diastolic for 2238 “nonintervened” individuals, ie, those without special diet/nutritional supplements or diagnosis/treatment for cardiovascular disease or diabetes. Dietary calcium and magnesium, correlated with phosphorus (partial r =0.71 and r =0.68), were inversely associated with blood pressure. Blood pressures were lower by 1.9 to 4.2 mm Hg systolic/1.2 to 2.4 mm Hg diastolic for people with intakes above versus below country-specific medians for all 3 of the minerals. These results indicate the potential for increased phosphorus/mineral intake to lower blood pressure as part of the recommendations for healthier eating patterns for the prevention and control of prehypertension and hypertension.

Introduction: Twenty-four-hour (24-h) urine excretion is the “gold standard” for estimation of sodium intake. Sodium intake assessed by 24-h dietary recall has been reported to correlate with urinary sodium excretion, and is considered reliable for assessing population sodium intake. However, the validity of 24-h dietary recall across countries has rarely been studied. The present study aims to compare the 24-h dietary recall with 24-h urine collection for the estimation of population sodium intake in different countries. Methods: Data from the International study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) were used in the analyses, including 4680 men and women ages 40-59 years from 17 population samples in China, Japan, UK and USA. Four 24-h dietary recalls and two timed 24-h urine samples were collected for each participant; the averages of the dietary and urinary sodium measurements were used. The correlation and difference between the two methods were then explored and compared across countries. Results: After adjustment for population sample and gender, a significant correlation was found in all four countries between dietary and urinary sodium measurements (r=0.33, 0.45, 0.36 and 0.46 for China, Japan, UK and USA respectively, P Conclusions: The correlation of sodium intake estimated by the two methods is similar (0.33-0.46) for the four countries, and the 24-h dietary recall data demonstrate great accuracy in assessing sodium intake at the population level for Japan, UK and USA. For Chinese populations, however, the 24-h urine collection is preferable to the 24-h dietary recall since dietary recalls yielded considerable underestimation of sodium intake.

Background: High body mass index (BMI) and diabetes have been linked to risk of non-Hodgkin's lymphoma (NHL), but results are inconsistent and most studies use self-reported information. No study has evaluated the association of NHL with postload plasma glucose (PLG) levels, which are positively associated with BMI. We analyzed data from a cohort study to investigate associations of interviewer-measured BMI and PLG with risk of NHL mortality and to explore associations with leukemia and multiple myeloma.Methods: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1967 to 1973. Height and weight were measured by study nurses. A 50-g oral glucose load was administered to nondiabetic participants. Of the at-risk cohort of 35,420 men and women, 129 died of NHL, 151 died of leukemia, and 66 died of multiple myeloma during an average of 31 years of follow-up. Hazard Ratios (HR) and 95% confidence intervals (95% CI) were derived from Cox proportional hazards regression models.Results: Among men, there were positive dose-response relations of BMI with mortality from NHL (HR, 2.57; 95% CI, 1.24-5.34 for the highest versus lowest quartile; Ptrend = 0.01) and leukemia (HR, 1.98; 1.07-3.69; Ptrend = 0.02). PLG also was positively related to NHL mortality (HR, 2.86; 95% CI, 1.35-6.06 for the highest versus lowest category; Ptrend = 0.004). For women, a higher BMI was positively associated with leukemia mortality (HR, 2.47; 95% CI, 0.96-6.36; Ptrend = 0.02) and the highest level of PLG was associated with risk of mortality from multiple myeloma (HR, 3.06; 95% CI, 1.05-8.93). The risk estimates for BMI and PLG remained unchanged after adjustment for each factor.Conclusions: High BMI and/or abnormal PLG is associated with higher risk of mortality from NHL and possibly leukemia and from myeloma in women. These findings might have public health significance because BMI and glucose levels are amenable to modification. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2348–54)

Objective: Hip-Hop to Health Jr. was a diet/physical activity intervention designed to reduce gains in BMI (kilograms per meter squared) in preschool minority children. Research Methods and Procedures: Twelve predominantly Latino Head Start centers participated in a group-randomized trial conducted between Fall 2001 and Winter 2003. Six centers were randomized to a culturally proficient 14-week (three times weekly) diet/physical activity intervention. Parents participated by completing weekly homework assignments. The children in the other six centers received a general health intervention that did not address either diet or physical activity. The primary outcome was change in BMI, and secondary outcomes were changes in dietary intake and physical activity. Measures were collected at baseline, post-intervention, and at Years 1 and 2 follow-up. Results: There were no significant differences between intervention and control schools in either primary or secondary outcomes at post-intervention, Year 1, or Year 2 follow-ups. Discussion: When Hip-Hop to Health Jr. was conducted in predominantly black Head Start centers, it was effective in reducing subsequent increases in BMI in preschool children. In contrast, when the program was conducted in Latino centers, it was not effective. Although the intervention did not prevent excessive weight gain in Latino children, it was very well received. Future interventions with this population may require further cultural tailoring and a more robust parent intervention.