Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies

Background: Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results. Materials and methods: In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR_G). Cumulative and recursive cumulative meta-analyses were also performed.ResultsThe analysis showed marginal significant association for the C677T variant, overall [OR = 0.91 (0.82–1.00) and OR_G = 0.89 (0.79–1.01)], and in Whites [OR = 0.88 (0.77–0.99) and OR_G = 0.85 (0.73–0.99)]. The A1298C variant produced non-significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta-analysis indicated lack of sufficient evidence for denying or claiming an association. Conclusion: The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL.     

Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: Based on published genome-wide association studies in a central Chinese population

A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G > T and rs2274224 C > G) of PLCE1 in a population-based case–control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45–5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46–0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (P_trend = 0.005). The G_rs17417407A_rs2274223C_rs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62–0.93), meanwhile the G_rs17417407G_rs2274223C_rs2274224 and T_rs17417407G_rs2274223C_rs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33–2.18 and OR, 2.51; 95% CI, 1.15–2.49). Gene–environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the “high risk group” with 3.67-fold (OR: 3.67, 95% CI: 2.74–4.92), compared to the “low risk group”. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.     

Urinary F2‐Isoprostanes Are Not Associated with Increased Risk of Type 2 Diabetes

Objective: Free radicals have been implicated in the etiology of type 2 diabetes. Cross‐sectional studies have demonstrated associations between oxidative damage and type 2 diabetes. However, no prospective data on this association are available. Research Methods and Procedures: A case control study was conducted within the prospective cohort of the Insulin Resistance Atherosclerosis Study: 26 cases who developed type 2 diabetes in the follow‐up period and 26 controls who remained free of type 2 diabetes were randomly selected. Oxidative status was assessed by measuring 2, 3‐dinor‐5, 6‐dihydro‐15‐F_2t‐isoprostane (F₂‐IsoPM) in baseline urine samples using gas chromatography/mass spectroscopy. Type 2 diabetes was defined by serial oral glucose tolerance tests and World Health Organization criteria. Results: Urinary F₂‐IsoPM varied between 0.18 and 2.60 ng/mg creatinine; 25th/50th/75th percentiles were 0.42, 0.60, and 0.89, respectively. A trend toward higher levels were observed in women and in persons with impaired glucose tolerance at baseline (p = 0.1). F₂‐IsoPM increased with BMI (r = 0.36, p = 0.01). After adjustment for age, gender, baseline impaired glucose tolerance status, and BMI, F₂‐IsoPM levels were inversely associated with development of type 2 diabetes: odds ratio = 0.32 (95% confidence interval, 0.12 to 0.81) for the difference between the 75th and 25th percentiles. Discussion: These results suggest that oxidative damage is not a cause of type 2 diabetes. Positive cross‐sectional associations of F₂‐IsoPM with the risk factors for diabetes, BMI, and impaired glucose tolerance and inverse associations with development of type 2 diabetes indicate that F₂‐IsoPM might reflect a compensatory mechanism.     

Evaluation of the Influence of Cardiorespiratory Fitness on Diverse Health Risk Factors,Independent of Waist Circumference,in 40‐Year‐Old Flemish Males

Objective: To examine whether cardiorespiratory fitness is associated with health risk factors, independent of abdominal obesity (waist circumference). Research Methods and Procedures: Data from 141 40‐year‐old Flemish male subjects were used in a cross‐sectional design. The main outcome measure in this study was the health risk profile, composed of lipid parameters, blood pressure, and body composition parameters. Data were analyzed by regression analysis and by means of analysis of covariance with waist circumference (WC) as covariate and cardiorespiratory fitness as source of variance. Results: The data demonstrated that cardiorespiratory fitness was significantly associated with triglycerides, with the ratio of total cholesterol/serum high density lipoprotein cholesterol, and with percent body fat, independent of an association with WC. Discussion: Major findings of the present cross‐sectional study indicate that a high WC is associated with adverse health‐related lipid profile and body composition characteristics and that relatively high levels of aerobic fitness attenuate the health risk associated with a large WC.     

Confidence Intervals of the Attributable Risk under Cross‐Sectional Sampling with Confounders

Since it can account for both the strength of the association between exposure to a risk factor and the underlying disease of interest and the prevalence of the risk factor, the attributable risk (AR) is probably the most commonly used epidemiologic measure for public health administrators to locate important risk factors. This paper discusses interval estimation of the AR in the presence of confounders under cross‐sectional sampling. This paper considers four asymptotic interval estimators which are direct generalizations of those originally proposed for the case of no confounders, and employs Monte Carlo simulation to evaluate the finite‐sample performance of these estimators in a variety of situations. This paper finds that interval estimators using Wald's test statistic and a quadratic equation suggested here can consistently perform reasonably well with respect to the coverage probability in all the situations considered here. This paper notes that the interval estimator using the logarithmic transformation, that is previously found to consistently perform well for the case of no confounders, may have the coverage probability less than the desired confidence level when the underlying common prevalence rate ratio (RR) across strata between the exposure and the non‐exposure is large (≥4). This paper further notes that the interval estimator using the logit transformation is inappropriate for use when the underlying common RR ≐ 1. On the other hand, when the underlying common RR is large (≥4), this interval estimator is probably preferable to all the other three estimators. When the sample size is large (≥400) and the RR ≥ 2 in the situations considered here, this paper finds that all the four interval estimators developed here are essentially equivalent with respect to both the coverage probability and the average length.     

Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA Study

Objective: Epidemiological studies showing an association between the melanocortin‐4‐receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators. Methods and Procedures: We analyzed this polymorphism in 7,888 adults of a population‐based cross‐sectional study applying regression‐based statistical models. Results: Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (–1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA_1c) (–0.09%, P = 0.040), and increased HDL‐cholesterol (HDL‐C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA_1c and HDL‐C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness. Discussion: Our representative study of well‐phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient‐related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.     

Describing Ordinal Odds Ratios for Stratified r × c Tables

For an r × ctable with ordinal responses, odds ratios are commonly used to describe the relationship between the row and column variables. This article shows two types of ordinal odds ratios where local‐global odds ratios are used to compare several groups on a c‐category ordinal response and a global odds ratio is used to measure the global association between a pair of ordinal responses. When there is a stratification factor, we consider Mantel‐Haenszel (MH) type estimators of these odds ratios to summarize the association from several strata. Like the ordinary MH estimator of the common odds ratio for several 2 × 2 contingency tables, the estimators are used when the association is not expected to vary drastically among the strata. Also, the estimators are consistent under the ordinary asymptotic framework in which the number of strata is fixed and also under sparse asymptotics in which the number of strata grows with the sample size. Compared to the maximum likelihood estimators, simulations find that the MH type estimators perform better especially when each stratum has few observations. This article provides variances and covariances formulae for the local‐global odds ratios estimators and applies the bootstrap method to obtain a standard error for the global odds ratio estimator. At the end, we discuss possible ways of testing the homogeneity assumption.     

MDR1 mRNA expression and MDR1 gene variants as predictors of response to chemotherapy in patients with acute myeloid leukaemia: a meta-analysis

Abstract

Data from 30 pharmacogenomic studies that investigated MDR1 mRNA expression or gene variants (C3435T, G2677TA, C1236T) and response to therapy in acute myeloid leukaemia (AML) were synthesized. Anthracycline-based regimens were mainly used. MDR1 mRNA overexpression was associated with poor response to therapy [odds ratio (OR)?=?2.49 95% confidence interval (CI) 1.38–4.50]. The gene variants were not associated with response to treatment; the generalized ORs, a genetic model-free approach, for the variants C3435T, G2677TA and C1236T were OR_G?=?0.86 (95% CI 0.55–1.37), OR_G?=?0.97 (95% CI 0.58–1.64) and OR_G?=?1.17 (95% CI 0.75--1.83), respectively. There is indication that MDR1 mRNA expression may be considered as a potential marker for response to chemotherapy in AML patients.     

The Effect of Extremely Low‐Frequency Electromagnetic Fields on the Prevalence of Musculoskeletal Disorders and the Role of Oxidative Stress

Extremely low‐frequency electromagnetic fields (ELF‐EMFs) may cause negative health effects. This study aimed to investigate the direct and indirect effects of chronic exposure to extremely low‐frequency electric and magnetic fields on the prevalence of musculoskeletal disorders (MSDs). In this cross‐sectional study, 152 power plant workers were enrolled. The exposure level of employees was measured based on the IEEE Std C95.3.1 standard. Superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) (independent variables) were measured in the serum of subjects. The Nordic musculoskeletal questionnaire was used to assess MSDs (dependent variable). The mean exposure of electric and magnetic fields were 4.09 V/m (standard deviation [SD] = 4.08) and 16.27 µT (SD = 22.99), respectively. Increased levels of SOD, Cat, GPx, and MDA had a direct significant relation with MSDs. In the logistic regression model, SOD (odds ratio [OR] = 0.952, P = 0.026), GPx (OR = 0.991, P = 0.048), and MDA (OR = 0.741, P = 0.021) were significant predictors of MSDs. ELF‐EMFs were not related to MSDs directly; however, increased levels of oxidative stress may cause MSDs. Bioelectromagnetics. 2019;40:354–360. © 2019 Bioelectromagnetics Society.     

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID‐north population with 694 AF cases and 710 controls, adjusted P_‐adj = 6.25 × 10^?3 with an odds ratio was 0.77, GeneID‐central population with 1106 cases and 1501 controls, P_‐adj = 9.88 × 10^?5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non‐hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.     

High childhood obesity in an Australian population

Objective: The objective was to determine the prevalences of overweight and obesity in regional Australian children and to examine the association between BMI and indicators of socioeconomic status (SES). Research Methods and Procedures: Regionally representative cross‐sectional survey of 2184 children, 4 to 12 years of age, was conducted, and the socio‐demographic characteristics of their parents from regional Victoria, Australia, 2003 to 2004, were obtained. Results: The prevalences of overweight and obesity were 19.3 ± 0.8% (proportion ± standard error) and 7.6 ± 0.6%, respectively, using international criteria, and the proportion of overweight/obese girls was significantly higher than that of boys (29.6 ± 1.4% vs. 23.9 ± 1.3%, χ² = 9.01, p = 0.003). Children from households of lower SES had higher odds of being overweight/obese; lower SES was defined by lower paternal education (adjusted odds ratio, 1.18; 95% confidence interval, 1.08 to 1.30) and lower area‐level SES (adjusted odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25), adjusted for age, gender, height, and clustering by school. Discussion: The prevalences of overweight and obesity are increasing in Australian children by about one percentage point per year. This equates to ～40,000 more overweight children each year, placing Australian children among those at highest risk around the world. In addition, girls are more likely to be overweight, and there is a general trend for children of lower SES to be at even greater risk of overweight and obesity.     

Birth Weight,Adult Body Composition,and Subcutaneous Fat Distribution

Objectives: To investigate if birth weight is related to both body mass index (BMI) and distribution of subcutaneous fat at adult age. Research Methods and Procedures: A 9‐year longitudinal study was performed in 229 subjects (192 women) with ages ranging from 27 to 36 years. Birth weight was retrieved by a questionnaire, and adult weight, height, skinfold thicknesses, and waist‐to‐hip ratio (WHR) were repeatedly measured at mean ages 27, 29, 31, and 36 years. BMI, sum of four skinfolds (S4S), the ratio between two truncal skinfolds and S4S (SS/S4S), and the ratio between WHR and the cross‐sectional area of the left thigh were calculated with the available data. Results: The adjusted model showed that in women, birth weight was significantly negatively related to adult S4S [β = ?5.211; (?9.768 to ?0.654)], waist circumference [β = ?1.449; (?2.829 to ?0.069)], and SS/S4S ratio [β = ?3.579; (?5.296 to ?1.862)]. In men, a significant negative association was observed between birth weight and adult WHR [β = ?1.096; (?2.092 to ?0.100)] only. Other relationships showed, although not significantly, the same negative trend, namely that lower birth weight is related to higher adult body fat mass (S4S) and a more truncal subcutaneous fat distribution (SS/S4S). No associations were found between birth weight and either adult BMI or the cross‐sectional area of the thigh. Discussion: Lower birth weight is, in both adult men and women, related to a higher adult subcutaneous fat mass and a more truncal distribution of subcutaneous fat, indicating a higher risk for obesity.     

Genetic variation in catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase (<Emphasis Type="Italic">COMT</Emphasis>) and obesity in the prostate,lung, colorectal,and ovarian (PLCO) cancer screening trial

Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had >30% increases in BMI from ages 20 to 50 years, compared to those with 0–5% increase in BMI (0–5%) over the same age period: (CC is referent; OR_CG = 1.42, OR_GG = 1.46, P _trend = 0.06). By sex, the increased risk was further pronounced among females (OR_CG = 1.50, OR_GG = 2.10, P _trend = 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were more likely than individuals with 0–5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T–COMT Ex4-76 C > G–COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: OR_C-G-G = 1.33, 95% CI 1.01–1.77) and C-G-A (OR_C-G-A = 1.79, 95% CI 0.72–4.49). We observed no association between any of the COMT polymorphisms with smoking behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears to play a role in large increases in BMI. The null association with smoking and alcohol and the pronounced association with increasing BMI among women further implicates COMT’s role in estrogen metabolism as a potentially culpable pathway. Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity.     

Effects of UV-B radiation on growth rates,pigment content and ultrastructure of red (wild type), greenish-brown and green strains of Gracilaria birdiae (Gracilariales,Rhodophyta)

Based on physiological characteristics, we hypothesized that different strains of Gracilaria birdiae from two distinct geographical areas of the Brazilian coast (2500 km apart) would have different responses to long-term exposure to UV-B radiation (UV-B). The locations differ in their environmental conditions: one is a warmer area, Ceará State (CE), closer to the equator; the other is a colder area, Espirito Santo State (ES), closer to the Tropic of Capricorn. To test the hypothesis that the CE population is more resistant to UV-B than the ES population, apical segments of the red (RD_CE, RD_ES), green (GR_CE) and greenish-brown (GB_CE) strains were cultivated in the laboratory under two treatments: control (PAR) and artificial UV-B (PAR + UV-B). Algal performance was evaluated by considering growth rates, pigment content and ultrastructural analysis. Compared with the control, all strains showed a decrease in growth rates after exposure to UV-B. Of all strains, RD_ES showed the greatest sensitivity to UV-B. However, a decrease in growth rate and morphological changes were observed to a lesser extent in the RD_CE strain. Moreover, exposure to UV-B resulted in a decrease in the concentrations of phycobiliproteins in the RD_CE strain. The GB_CE strain showed an increase in phycoerythrin (PE)/allophycocyanin (APC) and phycocyanin (PC)/allophycocyanin (APC) ratios after exposure to UV-B, suggesting this strain had a higher tolerance to the radiation. No differences in the chlorophyll a and carotenoid content were found between the control and UV-B treated samples for all strains. Ultrastructural changes, such as damage to chloroplasts and mitochondria, were present in all strains after exposure to UV-B. In summary, our findings support the hypothesis that the population from Ceará State has adapted to the higher irradiation and is thus more resistant to increased UV-B. Additionally, of the strains tested, the GB_CE and RD_CE strains appear to be more resistant to this radiation.     

Relationships of Psychiatric Disorders with Overweight and Obesity in an Adult General Population**

Objective: To explore relationships of smoking and risk drinking status, nicotine and alcohol dependence, and anxiety, depressive, and somatoform disorders with overweight and obesity. Research Methods and Procedures: A probability sample was drawn that was representative for the adult general population, 18 to 64 years of age, in one region of Germany; the participation rate was 70.2%. After excluding those who were pregnant or had a current eating disorder according to the DSM‐IV, 4063 individuals remained. Overweight and obesity were defined according to the BMI that was assessed in the face‐to‐face in‐home standardized interview (Composite International Diagnostic Interview) on psychiatric disorders. Results: Men with a former nicotine dependence had higher odds of being overweight than men who never had a nicotine dependence (adjusted odds ratio, 1.5; confidence interval, 1.1 to 2.1). Men at current risk for drinking and current alcohol‐dependent or abusing men had lower odds of being overweight compared with men who never were alcohol dependent, abusing, or at risk for drinking (adjusted odds ratio, 0.3; confidence interval, 0.8 to 0.9). Effect sizes were small. No relationship of overweight with depressive, anxiety, or somatoform disorders was found in the multivariate analysis. Discussion: There is a relationship between being overweight and nicotine and alcohol dependence or abuse among men but not among women. Even though one reason for women to refrain from quitting smoking is the fear of weight gain, these results do not support this. This information could help convince women to try to quit smoking.     

What is genetic differentiation,and how should we measure it—GST,D, neither or both?

Estimates of the fixation index, F_ST, have been used as measures of population differentiation for many decades. However, there have been persistent voices in the literature suggesting that these statistics do not measure true differentiation. In particular, the statistics Nei's G_ST and Wier and Cockerham's θ have been criticized for being ‘constrained’ to not equal one in some situations that seem to represent maximal differentiation. Here, we address the issue of how to evaluate exactly how much information a particular statistic contains about the process of differentiation. This criterion can be used to counter most concerns about the performance of G_ST (and related statistics), while also being reconciled with the insights of those who have proposed alternative measures of differentiation. In particular, the likelihood‐based framework that we put forward can justify the use of G_ST as an effective measure of differentiation, but also shows that in some situations G_ST is insufficient on its own and needs supplementing by another measure such as Jost's D or Hedrick's G′_ST. This approach will become increasingly important in the future, as greater emphasis is placed on analysing large data sets.     

Rapid infant weight gain predicts childhood overweight

Objective : To determine among a contemporary cohort whether rapid weight gain between birth and 6 months is associated with risk of childhood overweight and if this risk differs by ethnicity and/or breast‐feeding history. Research Methods and Procedures : This was a cross‐sectional survey in 1999 to 2000 of parents/guardians of children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children in New York State. Measurements were abstracted by chart review, including weight at birth and 6 months, and height and weight at time of survey and every 6 months subsequently. Overweight at 4 years of age was defined as a BMI ≥ 95th age‐ and sex‐specific percentiles. Results : The study sample was 32% Hispanic, 19% black, and 49% white; 17% of children were overweight. Rate of infant weight gain (expressed in terms of 100 g/mo) was significantly associated with being overweight at 4 years (odds ratio, 1.4; 95% confidence interval, 1.3 to 1.6 after adjusting for history of breast‐feeding, birth weight, and ethnicity). The odds of being overweight at 4 years of age for Hispanic children were twice those of non‐Hispanic children (odds ratio, 2.2; 95% confidence interval, 1.5 to 3.3). The population‐attributable risk of overweight at 4 years of age was 19% for children in the highest quintile of infant weight gain. Discussion : Among this contemporary, multi‐ethnic cohort, rapid infant weight gain was associated with increased risk of being overweight at 4 years of age, independently of potential confounders. Identification of the risk factors contributing to rapid weight gain during infancy might improve early recognition and guide strategies for optimal nutrition to prevent the development of childhood overweight.     

Overweight,Waist Circumference,Age, Gender,and Insulin Resistance as Risk Factors for Hyperleptinemia

Objective: To evaluate the influence of overweight, waist circumference, age, gender, and insulin resistance as risk factors for hyperleptinemia. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 197 subjects: 59 men (21 aged <60 years and 38 aged ≥60 years) and 138 women (37 aged <60 years and 101 aged ≥60 years). The groups were stratified by overweight and normal weight. After a 12‐hour fasting period, we measured serum leptin and insulin levels with radioimmunoassay methods. We also measured serum glucose and lipid profile. The data were analyzed by means of comparative tests. A variance‐stabilizing transformation (natural logarithmic) was used to meet multiple linear regression, analysis of covariance, and logistic regression models. Results: The leptin serum levels were higher and statistically significant in young and older women than they were in men. We observed an interaction between gender and body mass index to explain the difference in leptin levels (p < 0.0001). Our study demonstrated an inverse relationship between leptin with age and high‐density lipoprotein cholesterol. In logistic regression analysis, the overweight × gender interaction and waist circumference have a statistically significant influence as independent variables on hyperleptinemia (overweight × gender odds ratio = 6.81; 95% confidence interval, 1.10 to 46.86; p < 0.05 and waist circumference odds ratio = 4.34; 95% confidence interval, 1.47 to 12.83; p = 0.001). Discussion: Women who were overweight or had a higher waist circumference (women ≥ 88 cm and men ≥ 102 cm) have a significantly higher risk of having hyperleptinemia. The increase in age as an isolated variable is not a risk factor for hyperleptinemia.     

Alcohol intake, insulin resistance, and abdominal obesity in elderly men

Objective: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. Research Methods and Procedures: In a population‐based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insulin secretion (early insulin response), or adiposity [BMI, waist circumference (WC), waist‐to‐hip ratio]. Alcohol intake was self‐reported (questionnaire) and was assessed from a validated 7‐day dietary record. The cross‐sectional associations were evaluated using multivariable linear regression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. Results: In multivariable models, self‐estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (β‐coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p = 0.02) and waist‐to‐hip ratio (0.006 [0.002–0.009], p = 0.003). The association with WC and waist‐to‐hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. Discussion: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers.