Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysis.

BACKGROUND/OBJECTIVES: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear. SUBJECT/METHODS: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. RESULTS: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. CONCLUSIONS: A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

Intake of ruminant trans-fatty acids, assessed by diet history interview, and changes in measured body size, shape and composition.

OBJECTIVE: Studies have suggested that total intake of trans-fatty acids (TFA) is positively associated with changes in body weight and waist circumference, whereas intake of TFA from ruminant dairy and meat products (R-TFA) has not been associated with weight gain. However, these previous studies are limited by self-reported measures of body weight and waist circumference or by a cross-sectional design. The objective of the present study was to investigate if R-TFA intake was associated with subsequent changes in anthropometry (body weight, waist and hip circumference) measured by technicians and body composition (body fat percentage). DESIGN: A 6-year follow-up study. Information on dietary intake was collected through diet history interviews, and anthropometric and bioelectrical impedance measurements were obtained by trained technicians at baseline (1987-1988) and at follow-up (1993-1994). Multiple regression with cubic spline modelling was used to analyse the data. SETTING: Copenhagen County, Denmark. SUBJECTS: Two hundred and sixty-seven men and women aged 35-65 years from the Danish MONICA (MONItoring of trends and determinants in CArdiovascular diseases) cohort. RESULTS: The median R-TFA intake was 1.3 g/d (5th, 95th percentile: 0.4, 2.7 g/d) or 0.6% of the total energy intake (5th, 95th percentile: 0.2, 1.1%). No significant associations were observed between R-TFA intake and changes in body weight, waist and hip circumference or body fat percentage. CONCLUSIONS: R-TFA intake within the range present in the Danish population was not significantly associated with subsequent changes in body size, shape or composition and the 95% confidence intervals indicate that any relevant associations are unlikely to have produced these observations.

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia.

BACKGROUND: High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk. OBJECTIVES: We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity. METHODS: A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations, adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models. RESULTS: WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WHR with postprandial TG (ß = 0.038 µmol/L*min, SE = 0.019 µmol/L*min, P = 0.044) and RLP cholesterol concentrations (ß = 0.059 mmol/L, SE = 0.025 mmol/L, P = 0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations. CONCLUSIONS: Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia.This trial was registered at www.isrctn.com as ISRCTN25867281.

Advancing the future of physical activity guidelines in Canada: an independent expert panel interpretation of the evidence.

The Canadian Society for Exercise Physiology, in partnership with the Public Health Agency of Canada, has initiated a review of their physical activity guidelines to promote healthy active living for Canadian children, youth, adults and older adults; previous guidelines were released in 2002, 2002, 1998 and 1999 respectively. Several background papers from this project were published recently and provide foundation evidence upon which to base new guidelines. Furthermore, comprehensive systematic reviews were completed to ensure a rigorous evaluation of evidence informing the revision of physical activity guidelines for asymptomatic populations. The overall guideline development process is being guided and assessed by the AGREE II instrument. A meeting of experts was convened to present the evidence complied to inform the guideline revisions. An independent expert panel was assembled to review the background materials and systematic reviews; listen to the presentations and discussions at the expert meeting; ask for clarification; and produce the present paper representing their interpretation of the evidence including grading of the evidence and their identification of needs for future research. The paper includes also their recommendations for evidence-informed physical activity guidelines.

Body height in young adult men and risk of dementia later in adult life.

This study examined the relationship between body height and dementia and explored the impact of intelligence level, educational attainment, early life environment and familial factors. A total of 666,333 men, 70,608 brothers, and 7388 twin brothers born 1939-1959 and examined at the conscript board were followed in Danish nationwide registers (1969-2016). Cox regression models were applied to analyze the association between body height and dementia. Within-brothers and within-twin pair analyses were conducted to explore the role of shared familial factors including partly shared genetics. In total, 10,599 men were diagnosed with dementia. The association between one z-score difference in body height and dementia (HR: 0.90, 95% CI: 0.89;0.90) was inverse and weakened slightly after adjustment for intelligence test scores and educational level. The associations persisted in within-brother analysis and revealed a stronger, but less precise, point estimate than the cohort analysis of brothers. The twin analysis showed similar, but imprecise estimates.

Increase in clinically recorded type 2 diabetes after colectomy.

The colon hosts gut microbes and glucagon-like peptide 1 secreting cells, both of which influence glucose homeostasis. We tested whether colectomy is associated with development of type 2 diabetes. Using nationwide register data, we identified patients who had undergone total colectomy, partial colectomy, or proctectomy. For each colectomy patient, we selected 15 non-colectomy patients who had undergone other surgeries. Compared with non-colectomy patients, patients with total colectomy (n = 3,793) had a hazard ratio (HR) of clinically recorded type 2 diabetes of 1.40 (95% confidence interval [CI], 1.21 to 1.62; p<0.001). Corresponding HRs after right hemicolectomy (n = 10,989), left hemicolectomy (n = 2,513), and sigmoidectomy (n = 13,927) were 1.08 (95% CI, 0.99 to 1.19; p=0.10), 1.41 (95% CI, 1.19 to 1.67; p<0.001) and 1.30 (95% CI, 1.21 to 1.40; p<0.001), respectively. Although we were not able to adjust for several potential confounders, our findings suggest that the left colon may contribute to maintenance of glucose homeostasis.

BMI at school age and incident asthma admissions in early adulthood: a prospective study of 310,211 children.

BACKGROUND: Excess body weight in adulthood is associated with risk for asthma admission (AA). Our aim was to investigate if this association also applies to the relation between body mass index (BMI) in childhood and AAs in early adulthood (age 20-45 years). METHODS: This was a prospective study of 310,211 schoolchildren (born 1930-1989) from the Copenhagen School Health Records Register. Height and weight were measured annually, and generated BMI z-scores were categorized as low (lower quartile), normal (interquartile) and high (upper quartile). Associations between BMI at ages 7-13 and AA were estimated by Cox regressions, and presented as hazard ratios (HRs) and 95% confidence intervals (CI). Main outcome was incident hospital AAs (extracted from the Danish National Patient Register) in early adulthood. RESULTS: During 4,708,607 person-years of follow-up, 1,813 incident AAs were observed. Nonlinear associations were detected between childhood BMI and AAs. The risk of AA increased for females in the highest BMI category in childhood, with the highest HR of 1.3 (95% CI 1.16-1.55) at the age of 13 years. By contrast, males in the low BMI category had a higher risk of AA in early adulthood, with the highest HR of 1.24 (95% CI 1.03-1.51) at the age of 12 years. Females with an increase in BMI between ages 7 and 13 years had an increased risk of AA compared with females with stable BMI (HR 1.28, 95% CI 1.10-1.50). CONCLUSION: The association between childhood BMI and AA in early adulthood is non-linear. High BMI increases the risk of AA in females, whereas low BMI increases the risk in males.

Pretreatment fasting plasma glucose and insulin modify dietary weight loss success: results from 3 randomized clinical trials.

Background: Which diet is optimal for weight loss and maintenance remains controversial and implies that no diet fits all patients.Objective: We studied concentrations of fasting plasma glucose (FPG) and fasting insulin (FI) as prognostic markers for successful weight loss and maintenance through diets with different glycemic loads or different fiber and whole-grain content, assessed in 3 randomized trials of overweight participants.Design: After an 8-wk weight loss, participants in the DiOGenes (Diet, Obesity, and Genes) trial consumed ad libitum for 26 wk a diet with either a high or a low glycemic load. Participants in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) Supermarket intervention (SHOPUS) trial consumed ad libitum for 26 wk the New Nordic Diet, which is high in fiber and whole grains, or a control diet. Participants in the NUGENOB (Nutrient-Gene Interactions in Human Obesity) trial consumed a hypocaloric low-fat and high-carbohydrate or a high-fat and low-carbohydrate diet for 10 wk. On the basis of FPG before treatment, participants were categorized as normoglycemic (FPG <5.6 mmol/L), prediabetic (FPG 5.6-6.9 mmol/L), or diabetic (FPG ≥7.0 mmol/L). Modifications of the dietary effects of FPG and FI before treatment were examined with linear mixed models.Results: In the DiOGenes trial, prediabetic individuals regained a mean of 5.83 kg (95% CI: 3.34, 8.32 kg; P < 0.001) more on the high- than on the low-glycemic load diet, whereas normoglycemic individuals regained a mean of 1.44 kg (95% CI: 0.48, 2.41 kg; P = 0.003) more [mean group difference: 4.39 kg (95% CI: 1.76, 7.02 kg); P = 0.001]. In SHOPUS, prediabetic individuals lost a mean of 6.04 kg (95% CI: 4.05, 8.02 kg; P < 0.001) more on the New Nordic Diet than on the control diet, whereas normoglycemic individuals lost a mean of 2.20 kg (95% CI: 1.21, 3.18 kg; P < 0.001) more [mean group difference: 3.84 kg (95% CI: 1.62, 6.06 kg); P = 0.001]. In NUGENOB, diabetic individuals lost a mean of 2.04 kg (95% CI: -0.20, 4.28 kg; P = 0.07) more on the high-fat and low-carbohydrate diet than on the low-fat and high-carbohydrate diet, whereas normoglycemic individuals lost a mean of 0.43 kg (95% CI: 0.03, 0.83 kg; P = 0.03) more on the low-fat and high-carbohydrate diet [mean group difference: 2.47 kg (95% CI: 0.20, 4.75 kg); P = 0.03]. The addition of FI strengthened these associations.Conclusion: Elevated FPG before treatment indicates success with dietary weight loss and maintenance among overweight patients consuming diets with a low glycemic load or with large amounts of fiber and whole grains. These trials were registered at clinicaltrials.gov as NCT00390637 (DiOGenes) and NCT01195610 (SHOPUS), and at ISRNCT.com as ISRCTN25867281 (NUGENOB).

Dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference.

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited.Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated.Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort (n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model.Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P-trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P-trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found.Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference.

Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and ß cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial.

Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes.Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss.Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15% protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40-45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of ß cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581.Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (ß ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B (P-interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (ß ± SE: -0.77 ± 0.40 µU/mL; P = 0.04) and HOMA-B (ß ± SE: -13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally (P = 0.10) and not significantly (P = 0.24) associated with insulin and HOMA-B, respectively.Conclusion:PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281.

Comparison of associations of maternal peri-pregnancy and paternal anthropometrics with child anthropometrics from birth through age 7 y assessed in the Danish National Birth Cohort.

BACKGROUND: Maternal prepregnancy adiposity may influence child adiposity beyond the transmitted genetic effects, which, if true, may accelerate the obesity epidemic, but the evidence for this mechanism is inconsistent. OBJECTIVE: The aim was to assess whether the associations of maternal body mass index (BMI) with child anthropometric measurements from birth through infancy and at 7 y of age exceed those of paternal associations. DESIGN: In the Danish National Birth Cohort, information on parental and child anthropometric measures is available for 30,655 trio families from maternal interviews during pregnancy and the postpartum period and from a 7-y follow-up. By using multiple linear and logistic regression models of child SD (z) scores of weight and BMI at birth, 5 mo, 12 mo, and 7 y of age, and of child overweight at age 7 y, we compared associations with maternal prepregnancy and postpartum BMI z scores and with paternal BMI z scores. RESULTS: When comparing maternal-child and paternal-child BMI z score associations, the strongest associations were observed with mothers' BMI at birth [maternal and paternal BMI z scores: 0.143 (95% CI: 0.130, 0.155) and 0.017 (95% CI: 0.005, 0.029), respectively] and throughout infancy, but the relative difference in the associations declined by child age [for BMI z score at child age 7 y per maternal and paternal BMI z scores: 0.208 (95% CI: 0.196, 0.220) and 0.154 (95% CI: 0.143, 0.166), respectively]. At 7 y of age, ORs of child overweight were 2.30 (95% CI: 1.99, 2.67) by maternal overweight and 1.96 (95% CI: 1.74, 2.21) by paternal overweight. There were no differences between the results based on maternal BMI before and after pregnancy or on child's weight adjusted for length or height. CONCLUSIONS: The associations of child weight and BMI with maternal BMI were stronger than with paternal BMI. The differences between the associations were strong at birth but declined with child aging.

Road Traffic and Railway Noise Exposures and Adiposity in Adults: A Cross-Sectional Analysis of the Danish Diet, Cancer, and Health Cohort.

BACKGROUND: Traffic noise has been associated with cardiovascular and metabolic disorders. Potential modes of action are through stress and sleep disturbance, which may lead to endocrine dysregulation and overweight. OBJECTIVES: We aimed to investigate the relationship between residential traffic and railway noise and adiposity. METHODS: In this cross-sectional study of 57,053 middle-aged people, height, weight, waist circumference, and bioelectrical impedance were measured at enrollment (1993-1997). Body mass index (BMI), body fat mass index (BFMI), and lean body mass index (LBMI) were calculated. Residential exposure to road and railway traffic noise exposure was calculated using the Nordic prediction method. Associations between traffic noise and anthropometric measures at enrollment were analyzed using general linear models and logistic regression adjusted for demographic and lifestyle factors. RESULTS: Linear regression models adjusted for age, sex, and socioeconomic factors showed that 5-year mean road traffic noise exposure preceding enrollment was associated with a 0.35-cm wider waist circumference (95% CI: 0.21, 0.50) and a 0.18-point higher BMI (95% CI: 0.12, 0.23) per 10 dB. Small, significant increases were also found for BFMI and LBMI. All associations followed linear exposure-response relationships. Exposure to railway noise was not linearly associated with adiposity measures. However, exposure > 60 dB was associated with a 0.71-cm wider waist circumference (95% CI: 0.23, 1.19) and a 0.19-point higher BMI (95% CI: 0.0072, 0.37) compared with unexposed participants (0-20 dB). CONCLUSIONS: The present study finds positive associations between residential exposure to road traffic and railway noise and adiposity.

Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference.

BACKGROUND: Intake of sugar-sweetened beverages is associated with obesity, and this association may be modified by a genetic predisposition to obesity. OBJECTIVE: We examined the interactions between a molecular genetic predisposition to various aspects of obesity and the consumption of soft drinks, which are a major part of sugar-sweetened beverages, in relation to changes in adiposity measures. DESIGN: A total of 4765 individuals were included in the study. On the basis of 50 obesity-associated single nucleotide polymorphisms that are associated with body mass index (BMI), waist circumference (WC), or the waist-to-hip ratio adjusted for BMI (WHRBMI), the following 4 genetic predisposition scores (GRSs) were constructed: a complete genetic predisposition score including all 50 single nucleotide polymorphisms (GRSComplete), a genetic predisposition score including BMI-associated single nucleotide polymorphisms (GRSBMI), a genetic predisposition score including waist circumference-associated single nucleotide polymorphisms (GRSWC), and a genetic predisposition score including the waist-to-hip ratio adjusted for BMI-associated single nucleotide polymorphisms (GRSWHR). Associations between soft drink intake and the annual change (Δ) in body weight (BW), WC, or waist circumference adjusted for BMI (WCBMI) and possible interactions with the GRSs were examined with the use of linear regression analyses and meta-analyses. RESULTS: For each soft drink serving per day, soft drink consumption was significantly associated with a higher ΔBW of 0.07 kg/y (95% CI: 0.01, 0.13 kg/y; P = 0.020) but not with the ΔWC or ΔWCBMI In analyses of the ΔBW, we showed an interaction only with the GRSWC (per risk allele for each soft drink serving per day: -0.06 kg/y; 95% CI: -0.10, -0.02 kg/y; P = 0.006). In analyses of the ΔWC, we showed interactions only with the GRSBMI and GRSComplete [per risk allele for each soft drink serving per day: 0.05 cm/y (95% CI: 0.02, 0.09 cm/y; P = 0.001) and 0.05 cm/y (95% CI: 0.02, 0.07 cm/y; P = 0.001), respectively]. Nearly identical results were observed in analyses of the ΔWCBMI CONCLUSIONS: A genetic predisposition to a high WC may attenuate the association between soft drink intake and BW gain. A genetic predisposition to high BMI as well as a genetic predisposition to high BMI, WC, and WHRBMI combined may strengthen the association between soft drink intake and WC gain. However, the public health impact may be limited.

Macro fat and micro fat: insulin sensitivity and gender dependent response of adipose tissue to isocaloric diet change.

The adipose cell-size distribution is a quantitative characterization of adipose tissue morphology. At a population level, the adipose cell-size distribution is insulin-sensitivity dependent, and the observed correlation between obesity and insulin resistance is believed to play a key role in the metabolic syndrome. Changes in fat mass can be induced by altered energy intake or even diet composition. These macroscopic changes must manifest themselves as dynamic adipose cell-size distribution alterations at the microscopic level. The dynamic relationship between these 2 independent measurements of body fat is unknown. In this study, we investigate adipose tissue dynamics in response to various isocaloric diet compositions, comparing gender- and insulin sensitivity-dependent differences. A body composition model is used to predict fat mass changes in response to changes in diet composition for 28 individuals, separated into 4 subgroups according to gender and insulin sensitivity/resistance. Adipose cell-size distribution changes in each individual are simulated with a dynamic model and parameters corresponding to lipid turnover and cell growth rates are determined for each subgroup to match the relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive to changes in energy intake and diet composition than insulin sensitive subjects. The different cell-size distribution changes of adipose cells of various sizes in different subject groups further suggest distinct modulations of adipose cell dynamics.

Interaction between genetic predisposition to obesity and dietary calcium in relation to subsequent change in body weight and waist circumference.

BACKGROUND: Studies indicate an effect of dietary calcium on change in body weight (BW) and waist circumference (WC), but the results are inconsistent. Furthermore, a relation could depend on genetic predisposition to obesity. OBJECTIVE: The objective was to examine whether genetic predisposition to higher body mass index (BMI), WC, or waist-hip ratio (WHR) interacts with dietary calcium in relation to subsequent annual change in BW (ΔBW) and WC (ΔWC). DESIGN: The study was based on 7569 individuals from the MONItoring trends and determinants of CArdiovascular disease Study, a sample from the Danish Diet, Cancer and Health Study and the INTER99 study, with information on diet; 54 single-nucleotide polymorphisms (SNPs) associated with BMI, WC, or WHR adjusted for BMI; and potential confounders. The SNPs were combined in 4 scores as indicators of genetic predisposition; all SNPs in a general score and a score for each of 3 phenotypes: BMI, WC, and WHR. Linear regression was used to examine the association between calcium intake and ΔBW or ΔWC adjusted for concurrent ΔBW. SNP score × calcium interactions were examined by adding product terms to the models. RESULTS: We found a significant ΔBW of -0.076 kg (P = 0.021; 95% CI: -0.140, -0.012) per 1000 mg Ca. No significant association was observed between dietary calcium and ΔWC. In the analyses with ΔBW as outcome, we found no significant interactions between the developed predisposition scores and calcium. However, we found a significant interaction between a score of 6 WC-associated SNPs and calcium in relation to ΔWC. Each risk allele was associated with a ΔWC of -0.043 cm (P = 0.038; 95% CI: -0.083, -0.002) per 1000 mg Ca. CONCLUSIONS: Our study suggests that dietary calcium relates weakly to BW loss. We found no evidence of a general association between calcium and ΔWC, but calcium may reduce WC among people genetically predisposed to a high WC. However, further replication of this finding is needed.

Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study.

BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain.

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

Late introduction of complementary feeding, rather than duration of breastfeeding, may protect against adult overweight.

BACKGROUND: Early nutrition may affect the risk of overweight in later life. OBJECTIVE: The objective was to explore the effect of the duration of breastfeeding (BF) and age at introduction of complementary feeding (CF) on body mass index (BMI) during childhood through adulthood. DESIGN: The study was based on a subsample of the Copenhagen Perinatal Cohort established in 1959-1961 (n = 5068). Information on BF and available information on CF (age of introduction of "spoon-feeding," "vegetables," "egg," "meat," and "firm food") and several covariates were collected in infancy and linked with information on BMI from follow-up examinations in childhood and adulthood at age 42 y. RESULTS: The median (10th, 90th percentiles) durations of any BF and age at introduction of spoon-feeding were 2.50 (0.23, 6.50) and 3.50 (2.00, 6.00) mo, respectively. After 1 y of age and throughout childhood and adolescence, no association between BF and BMI was found in regression models also adjusted for age at introduction of spoon-feeding and covariates. The risk of overweight at age 42 y decreased or tended to decrease with increasing age (in mo) at introduction of spoon-feeding [odds ratio (OR): 0.94; 95% CI: 0.86, 1.02], vegetables (OR: 0.90; 95% CI: 0.81, 0.98), meat (OR: 0.93; 95% CI: 0.87, 1.00), and firm food (OR: 0.92; 95% CI: 0.86, 0.98) but not egg (OR: 0.98; 95% CI: 0.91, 1.05). CONCLUSION: The findings of this study suggest that introduction of CF at a later age (within the range of 2 to 6 mo) is protective against overweight in adulthood but do not support a protective effect of a longer duration of BF.

Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy.

BACKGROUND: Although both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) may affect birth weight, their separate and joint associations with complications of pregnancy and delivery and with postpartum weight retention are unclear. OBJECTIVES: We aimed to investigate the combined associations of prepregnancy BMI and GWG with pregnancy outcomes and to evaluate the trade-offs between mother and infant for different weight gains. DESIGN: Data for 60892 term pregnancies in the Danish National Birth Cohort were linked to birth and hospital discharge registers. Self-reported total GWG was categorized as low (<10 kg), medium (10-15 kg), high (16-19 kg), or very high (>or=20 kg). Adjusted associations of prepregnancy BMI and GWG with outcomes of interest were estimated by logistic regression analyses. RESULTS: High and very high GWG added to the associations of high prepregnancy BMI with cesarean delivery and were strongly associated with high postpartum weight retention. Moreover, greater weight gains and high maternal BMI decreased the risk of growth restriction and increased the risk of the infant's being born large-for-gestational-age or with a low Apgar score. Generally, low GWG was advantageous for the mother, but it increased the risk of having a small baby, particularly for underweight women. CONCLUSIONS: Heavier women may benefit from avoiding high and very high GWG, which brings only a slight increase in the risk of growth restriction for the infant. High weight gain in underweight women does not appear to have deleterious consequences for them or their infants, but they may want to avoid low GWG to prevent having a small baby.