Unusual manifestation of gastric adenocarcinoma presenting with lymphedema, chylothorax, and chylous ascites.

A 62-year-old Thai man with a 2-year history of bilateral lymphedema and an unprovoked left axillary vein thrombosis presented with progressive leg, scrotal, and abdominal swelling, and shortness of breath. He denied any gastrointestinal symptoms. His lymphedema had initially been diagnosed as chronic filariasis due to positive blood tests for anti-filarial antibodies; however, treatment with anti-filarial drugs failed to improve his symptoms. Subsequently, he underwent surgical lymphaticovenular anastomosis with scrotal reduction, which proved to be of limited symptomatic relief. Later investigations revealed bilateral chylothorax and chylous ascites, with the presence of metastatic adenocarcinoma. Histopathological examination of the patient's skin and scrotum biopsy from his previous surgery revealed invasion of the lymphatics by neoplastic cells with signet ring cell formation. Gastroscopy uncovered a gastric mass, and biopsy confirmed the diagnosis of stage IV gastric adenocarcinoma with signet ring cell. He later received palliative chemotherapy. For the management of chyle leakage, he was prescribed a very low-fat diet and supplemented with parenteral nutrition. Despite treatment, he developed cutaneous metastasis and was transitioned to best supportive care. The patient passed away 14 months after diagnosis.

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

Postprandial hypoglycemia after ileocolic interposition and Billroth-II gastrojejunostomy: A case report.

Postprandial reactive hypoglycemia, or late dumping syndrome, is a common but underrecognized complication from bypass surgery. We report an unusual case of postprandial reactive hypoglycemia in a patient with a severe esophageal stricture from corrosive agent ingestion who underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy. A 22-year-old male patient with a one-year history of corrosive ingestion was referred to the hospital for a surgical correction of severe esophageal stricture. After the patient underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy, he experienced multiple episodes of gastroesophageal refluxsymptoms during nasogastric feeding and had onset of hypoglycemic symptoms. His plasma glucose level was 59 mg/dL. After we had intraoperatively re-inserted a jejunostomy tube bypassing the ileocolic interposition, and reintroduced enteral nutrition, his hypoglycemic symptoms resolved. We performed a mixed meal tolerance test by nasogastric tube, but the results did not show postprandial hypoglycemia. Although the specific mechanism is unclear, this case suggests gastroesophageal reflux to the ileal interposition may have caused a state of exaggerated hyperinsulinemic response and rebound hypoglycemia. To the best of our knowledge, we are the first to report case of postprandial hypoglycemia after ileocolic interposition, which may have been caused by exaggerated hyperinsulinemic response due to gastroesophageal reflux to the ileal interposition. This syndrome should be considered in the patient who has had ileocolic interposition surgery and has developed postprandial hypoglycemia.

Association of body mass index and dietary intake with mild cognitive impairment and dementia: a retrospective cohort study.

BACKGROUND: The prevalence of cognitive impairment in older adults is gradually increasing, and this is leading to many adverse outcomes. Common causes of cognitive impairment in advancing age are mild cognitive impairment (MCI) and dementia. However, how the nutritional status and nutrient intake are related to MCI and dementia is controversial. Therefore, we aimed to evaluate the association of body mass index (BMI) and dietary intake with the risk of MCI and dementia. METHODS: This retrospective cohort study involved 821 participants aged ≥ 50 years from a previous population-based cohort study: the Electricity Generating Authority of Thailand (EGAT) study in 2013-2014 (baseline) and 2018-2019 (follow-up). Dietary intake was recorded using a 12-month self-reported food frequency questionnaire. MCI and dementia were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using the Montreal Cognitive Assessment with ADL and the Kessler Psychological Distress Scale (K10) at study entry and at the 5-year follow-up. RESULTS: Among the 821 participants, the mean age was 60.0 ± 4.3 years, and the incidence rate of MCI and dementia was 42.5 and 11.2 per 1,000 person-years, respectively. The rate of MCI and dementia was higher in participants aged ≥ 60 years and with an education level of < 7 years. The rate of MCI was also higher in those with a BMI of ≥ 25 kg/m2 and type 2 diabetes. Compared to BMI 18.5-22.9 kg/m2, BMI of ≥ 25 kg/m2 (odds ratio 1.91 [95% confidence interval, 1.12-3.26], p < 0.001) was associated with an increased risk of MCI after adjusted for age, education level, and type 2 diabetes. Regarding dietary intake, fresh red meat consumption was inversely associated with the risk of MCI (p = 0.037) and dementia (p = 0.011) after adjusting for age, education level, type 2 diabetes, and BMI. CONCLUSION: Obesity was associated with a greater risk of MCI. Moreover, low consumption of fresh red meat could be a risk factor for MCI and dementia. Further studies are required to confirm and explain these findings.

Effect of Physical and Enzymatic Modifications on Composition, Properties and In Vitro Starch Digestibility of Sacred Lotus (Nelumbo nucifera) Seed Flour.

In this study, native lotus seed flour (N-LSF) was modified by different methods, namely, partial gelatinization (PG), heat−moisture treatment (HMT), or pullulanase treatment (EP). Their composition, functional properties, starch composition, and estimated glycemic index (eGI) were compared. PG contained similar protein, soluble dietary fiber, and insoluble dietary fiber contents to N-LSF, while those of HMT and EP differed from their native form. PG increased rapid digestible starch (RDS) but decreased resistant starch (RS); while HMT and EP increased amylose and RS contents to 34.57−39.23% and 86.99−92.52% total starch, respectively. Such differences led to the different pasting properties of the modified flours rather than PG, which was comparable to the native flour. HMT had limited pasting properties, while EP gave the highest viscosities upon pasting. The eGI of all samples could be classified as low (<50), except that of PG, which was in the medium range (60). It was plausible that lotus seed flour modified either with HMT or EP could be used as carbohydrate source for diabetes patients or health-conscious people.

Tropical Oil Consumption and Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta Analyses.

The health effects of saturated fat, particularly tropical oil, on cardiovascular disease are unclear. We investigated the effect of tropical oil (palm and coconut oils), lard, and other common vegetable oils (soybean and rice bran oils) that are widely used in tropical and Asian countries on lipid profiles. We performed an umbrella review of meta-analyses and systematic reviews. Electronic databases (Medline, Scopus, Embase, and Cochrane) were searched up to December 2018 without language restriction. We identified nine meta-analyses that investigated the effect of dietary oils on lipid levels. Replacement of polyunsaturated fatty-acid-rich oils (PUFAs) and monounsaturated FA-rich oils (MUFAs) with palm oil significantly increased low-density lipoprotein cholesterol (LDL-c), by 3.43 (0.44-6.41) mg/dL and 9.18 (6.90-11.45) mg/dL, respectively, and high-density lipoprotein cholesterol (HDL-c), by 1.89 (1.23-2.55) mg/dL and 0.94 (-0.07-1.97) mg/dL, respectively. Replacement of PUFAs with coconut oil significantly increased HDL-c and total cholesterol -by 2.27 (0.93-3.6) mg/dL and 5.88 (0.21-11.55) mg/dL, respectively-but not LDL-c. Substituting lard for MUFAs and PUFAs increased LDL-c-by 8.39 (2.83-13.95) mg/dL and 9.85 (6.06-13.65) mg/dL, respectively-but not HDL-c. Soybean oil substituted for other PUFAs had no effect on lipid levels, while rice bran oil substitution decreased LDL-c. Our findings show the deleterious effect of saturated fats from animal sources on lipid profiles. Replacement of unsaturated plant-derived fats with plant-derived saturated fats slightly increases LDL-c but also increases HDL-c, which in turn may exert a neutral effect on cardiovascular health.

Prevalence and predicting factors of metabolic-associated fatty liver disease diagnosed by transient elastography with controlled attenuation parameters in HIV-positive people.

Metabolic disorders are increasing in people living with HIV (PLWH), and metabolic associated fatty liver disease (MAFLD) has become a common complication. A cross-sectional study was conducted in HIV-positive persons receiving anti-retroviral therapy (ART), in order to determine the prevalence and predicting factors of MAFLD in PLWH. All participants underwent bioelectrical impedance analysis, ultrasonography, and transient elastography with controlled attenuation parameter (CAP). MAFLD was defined as CAP ≥248 dB/m. Significant fibrosis was defined when liver stiffness measurement >7.0 kPa. Predicting factors of MAFLD were determined using logistic regression analysis. Of 150 participants, 48 (32.0%) had MAFLD. Significant fibrosis was diagnosed in 5 (10.4%) participants in the MAFLD group. Blood pressure, waist circumference, body mass index (BMI), percentage of fat, serum transaminases, HbA1c, LDL, and triglycerides levels were significantly higher in the MAFLD group (p < 0.05). High BMI [odds ratio (OR) 1.596; 95% confidence interval (CI), 1.336-1.907, p < 0.001], triglycerides level >150 mg/dl [OR 3.722; 95% CI, 1.508-9.187, p < 0.004], and advanced age [OR 1.076; 95% CI, 1.017-1.139, p < 0.011] were associated with MAFLD in the multivariate analysis. MAFLD is common in PLWH receiving ART, while significant fibrosis is relatively infrequent. High BMI, age, and triglycerides level are the predicting factors of MAFLD in PLWH.

Bioimpedance Analysis-Guided Volume Expansion for the Prevention of Contrast-Induced Acute Kidney Injury (the BELIEVE Pilot Randomized Controlled Trial).

INTRODUCTION: Peri-procedural i.v. fluid administration is important for the prevention of contrast-induced acute kidney injury (CI-AKI). However, standardized fluid management protocols may not be suitable for all patients. We therefore wished to determine whether an individualized fluid administration protocol guided by measuring extracellular water (ECW) using bioimpedance analysis (BIA) would be safe and would reduce the incidence CI-AKI compared to a standardized fluid administration prescription. METHODS: In this pilot, randomized, parallel-group, single-blind, controlled trial, we compared the effect of BIA-guided isotonic bicarbonate administration according to the ratio of ECW to total body water (ECW/TBW) to our standard isotonic bicarbonate protocol in regard to the safety and efficacy of preventing CI-AKI in chronic kidney disease patients undergoing elective cardiac angiography. Our primary outcome was the incidence of CI-AKI, which was defined as a ≥0.3 mg/dl or 150% increase in serum creatinine concentration within 48 to 72 hours after cardiac angiography. RESULTS: We studied 61 patients, 30 in the bioimpedance group and 31 in the control group. Age was similar (72.5 ± 7 vs. 71.4 ± 7.9 years), as were body mass index (25.5 vs. 25.8 kg/m2) and baseline serum creatinine (1.3 ± 0.3 vs. 1.4 ± 0.4 mg/dl). The peri-procedural fluid volume administered was significantly greater in the BIA-guided hydration group (899.0 ± 252.7 ml vs. 594.4 ± 125.9 ml, P < .01). The incidence of CI-AKI was 3.3% in BIA-guided hydration group and 6.5% in the control group (relative risk = 0.52, 95% confidence interval = 0.05-5.40, P = 1.00). Adverse events reported were comparable between groups (6.7% vs. 6.5%, P = 1.00). CONCLUSIONS: The overall incidence of CI-AKI after cardiac angiography in our patients with mild-to-moderate renal insufficiency was lower than anticipated. Isotonic bicarbonate administration guided by bioimpedance measurements was safe, and probably led to a lower incidence of CI-AKI, although this not reach statistical significance.

Characteristics of hospitalized patients prescribed oral nutrition supplements in Thailand: A cross-sectional nutrition day survey.

BACKGROUND AND OBJECTIVES: Despite the proven benefits of oral nutrition supplements (ONS), its prescription in Thailand are far less than it should mainly due to limitation of reimbursement. Our aim was to compare hospital outcomes between hospitalized patients receiving only hospital food to those receiving hospital food with ONS. METHODS AND STUDY DESIGN: An annual cross-sectional survey, NutritionDay (nD), in Thailand was conducted in 2 hospitals from 2010 to 2015. The hospital outcomes were followed at day 30 after first evaluation. Logistic regression and Cox regression were performed to compare outcome between groups. RESULTS: 524 hospitalized patients, 472 with only hospital food and 52 with ONS, were included. Patients with ONS had longer hospital stay prior to recruitment, reported more physical dependencies, and ate less food. The ONS group was less likely to be discharged within 30 days as compared to hospital food group (unadjusted OR 0.28, 95% CI 0.16-0.52) but this effect was not significant after adjustment for length of stay before nD and PANDORA score (adjusted OR 0.62, 95% CI 0.3-1.34). Cox regression showed a trend to decreased rate of discharge within 30 days in the ONS group. CONCLUSIONS: This cross-sectional study showed a trend of worse outcomes associated with ONS prescription which might be related with higher mortality risk according to PANDORA score and longer previous hospital stay of the patients in the ONS group. Since the 2 studied groups were not comparable, further studies in this specific population should be performed.

The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D.

BACKGROUND: The complexity of vitamin D metabolites especially the contribution of C3-epimers of 25-hydroxyvitamin D (C3-epimers) in human sera remains unclear. We hypothesized that genetic polymorphisms in the vitamin D-related gene pathway contribute to variation in C3-epimer levels. Therefore, we investigated candidate single nucleotide polymorphisms (SNPs) concerning C3-epimer levels. METHODS: The candidate SNPs, including DHCR7/NADSYN1 (rs12785878), CYP2R1 (rs2060793) and GC (rs2282679), were genotyped in 1727 members of the third project of the Electricity Generating Authority of Thailand 3/1 cohort investigation. Each SNP was tested under three genetic effects (dominant, recessive and additive models) concerning the levels of total serum 25(OH)D [the sum of 25(OH)D2+3 and 3-epi-25(OH)D2+3], non-C3-epimers [25(OH)D2+3] and C3-epimers [3-epi-25(OH)D2+3], using linear regression analysis. RESULTS: Among the participants, the median (range) levels of non-C3-epimers and C3-epimers were 22.7 (6.4-49.2) ng/mL and 1.3 (0.01-14.2) ng/mL, respectively. In regression analysis, we found the genetic variation of two SNPs, the DHCR7/NADSYN1 (rs12785878; G > T) and GC (rs2282679; T > G) under additive genetic models, explained the variation of C3-epimer levels about 1.5% (p = 1.66 × 10-7) and 1.1% (p = 1.10 × 10-5), respectively. Interestingly, participants carrying the minor T-allele of rs12785878 exhibited a trend to increase C3-epimer levels, while those carrying the minor G-allele of rs2282679 exhibited a trend to decrease levels of both non-C3-epimers and C3-epimers. In addition, CYP2R1 (rs2060793; G > A) was clearly associated only with non-C3-epimer levels (p = 2.46 × 10-8). In multivariate analyses, sex, age and BMI were predictors for variation in C3-epimer concentration; sex and age for variation in non-C3-epimers. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate genetic models concerning the variation in C3-epimer levels. Our results emphasize that genetic determinants and the potential factors of C3-epimers differ from non-C3-epimers. This study contributes fundamental knowledge of the endogenous vitamin D pathway.

Unusual manifestation of vitamin A deficiency presenting with generalized xerosis without night blindness.

Vitamin A deficiency from malabsorption syndromes, including bariatric surgery, has become an emerging problem in developed countries. Early detection and prompt treatment lead to rapid and complete recovery. Nevertheless, it may result in irreversible blindness or death if left untreated. Health care personnel should be aware of this condition.

Transient Elastography in End-Stage Renal Disease Patients on Hemodialysis: The Effect of Net Fluid Withdrawal.

BACKGROUND/AIMS: The impact of volume status on liver stiffness measurement (LSM) as measured by transient elastography (TE) as in end-stage renal disease (ESRD) was unclear. We evaluated LSM before and after hemodialysis (HD) and identified the associated factors if the difference of LSM existed. METHODS: A cross-sectional study was conducted in ESRD patients on regular HD. Subjects underwent TE and bioelectrical impedance before and after HD. RESULTS: Thirty-six patients were enrolled. Mean (SD) net fluid withdrawal volume (NFWV) per session was 2.55 (0.9) l. Median (range) pre- and post-HD LSMs were 5.38 (2.8-25.7) and 5.4 (2.8-26) kPa, respectively (p = 0.712). Mean differences of pre- and post-HD LSMs correlated with NFWV (r = 0.49, 95% CI 0.19-0.71, p = 0.002). CONCLUSION: In ESRD on regular HD, LSM is not affected by HD. TE can be done before or after HD with similar results. However, fluid excess at pre-HD can cause inaccurately high LSM.

Vitamin D status is a determinant of skeletal muscle mass in obesity according to body fat percentage.

OBJECTIVES: Vitamin D deficiency is now being recognized as an emerging problem worldwide. Obesity has been found to be associated with lower serum 25-hydroxyvitamin D [25(OH)D] concentrations due to various mechanisms. There is increasing evidence showing the extraskeletal health benefit of vitamin D. Previous studies demonstrated the relationship between vitamin D and adiposity. However, the association between vitamin D status and skeletal muscle mass has not been established in healthy obese individuals in tropical countries. The aim of this cross-sectional study was to assess vitamin D status and its relationship to serum 25(OH)D concentrations and body composition, including skeletal muscle mass (SMM) and adiposity in healthy obese individuals without diabetes who live in Thailand, which is located near the equator. METHODS: We enrolled 163 obese Thai individuals (59.5% women) from the obesity clinic at the Ramathibodi Hospital, Mahidol University, in Bangkok, Thailand. RESULTS: The prevalence of vitamin D deficiency (<20 ng/mL) and vitamin D inadequacy (<30 ng/mL) were 49 (30.1%) and 148 (90.8%), respectively. In all, 98% of the individuals with body mass index >35 kg/m(2) had vitamin D inadequacy. Serum 25(OH)D concentrations were negatively associated with percent body fat (%BF) (r = -0.23; P = 0.003). Moreover, vitamin D status was positively associated with SMM (r = 0.18; P = 0.03) and the association remained after controlling for body fat mass and age (P = 0.003). Interestingly, in the individuals with lowest tertile of %BF, multiple linear regression analysis revealed that the significant positive predictors of %SMM were vitamin D status and male sex; the negative predictor was the body mass index after adjusting for age and exercise duration. CONCLUSIONS: Our study demonstrated the high prevalence of vitamin D deficiency in obese, Thai populations without diabetes. Vitamin D status was an independent predictor of %SMM of patients with lowest tertile of %BF. We speculated that adiposity might play a role in the relationship of vitamin D and SMM.

Work- and travel-related physical activity and alcohol consumption: relationship with bone mineral density and calcaneal quantitative ultrasonometry.

A number of healthy workers rarely exercise because of a lack of time or resources. Physical activity related to work and everyday travel may be more feasible, but evidence of its beneficial effect on bone health is scarce. We assessed if this form of physical activity was associated with higher bone mineral density (BMD) and stiffness index (SI) when adjusted for recreational physical activity, age, body mass index, smoking, alcohol consumption, education, and serum level of 25-hydroxyvitamin D. Healthy workers, aged 25-54 yr, of the Electricity Generating Authority of Thailand were surveyed. The outcomes were BMD (lumbar spine, femoral neck, and total hip) and calcaneal SI. Physical activity was estimated using the global physical activity questionnaire and considered active when >600 metabolic equivalent tasks (min). Of 2268 subjects, 74% were men. Active male subjects had significantly higher BMD at the femoral neck and total hip (p<0.005). However, the association was not significant with male lumbar spine BMD, male SI, or any bone parameters in women (p>0.05). In men, work and travel physical activity seems beneficial to male bone health; hence, it should be encouraged. Furthermore, smoking appeared harmful while moderate alcohol consumption was beneficial.

Causal relationship between body mass index and fetuin-A level in the asian population: a bidirectional Mendelian randomization study.

OBJECTIVE: Fetuin-A is associated with body mass index (BMI) as well as components of the metabolic syndrome. However, it is unclear if fetuin-A affects BMI or the other way around. We therefore assessed the causal association between fetuin-A and BMI or vice versa, utilizing a bidirectional Mendelian randomization approach. DESIGN AND METHODS: This was a study of 2558 subjects from the Electricity Generating Authority of Thailand (EGAT) cohort. Two polymorphisms, that is, rs2248690 in the alpha2-Hereman-Schmid glycoprotein (AHSG) gene and rs9939609 in the fat mass and obesity-associated (FTO) gene were genotyped. Bidirectional causal models were constructed using a two-stage least-square instrumental variable (IV) regression. First, rs2248690 locus was used as the instrumental variable for the effect of circulating fetuin-A on BMI, and then, the FTO rs9939609 locus was used as the instrumental variable for the effect of BMI on circulating fetuin-A. RESULTS: Among the 2558 subjects, the prevalence of the minor AHSG (T) and FTO (A) alleles was 17.9% and 22.1%, respectively. The AHSG rs2248690 locus was highly related to serum fetuin-A levels (P < 0.001). Likewise, the FTO rs9939609 locus and BMI were highly associated (P < 0.001). Mendelian randomization analyses showed that circulating fetuin-A, instrumented by the AHSG rs2248690 locus, was associated with BMI (coefficient = 2.26; 95% CI: 0.39, 4.12). In contrast, BMI, instrumented by the FTO rs9939609 locus, was not associated with circulating fetuin-A (coefficient = 0.0007; 95% CI: -0.0242, 0.0256). CONCLUSION: Our findings suggest a causal association leading from circulating fetuin-A to BMI. There was no evidence of reverse causality from BMI to fetuin-A.

Causal inference of the effect of adiposity on bone mineral density in adults.

OBJECTIVE: The causal effect of adipose tissue on bone mass and the direction of its net influence have not been directly assessed in adult humans. Using the Mendelian randomization analysis, we assessed the causality of adiposity in measurements of bone mass in adult males and females. DESIGN AND METHODS: Subjects consisted of 2154 adults aged 25-54 years from a cross-sectional cohort of the employees of the Electricity Generating Authority of Thailand. Body composition was determined after at least 3 h of fasting using multifrequency bioelectrical impedance analysis. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. A polymorphism in the fat mass and obesity-associated gene (FTO rs9939609) was used as an instrument in the Mendelian randomization analysis. RESULTS: The genotype distribution of the FTO rs9939609 polymorphism was 61·1% TT, 33·9% AT and 5·0% AA. The average body mass index (BMI), body fat mass and percentage body fat were 23·9 kg/m(2) (SD = 3·6), 17·9 kg (SD = 6·6) and 26·8% (SD = 7·2), respectively. The FTO rs9939609 polymorphism was significantly correlated with BMI (coefficient = 0·673 kg/m(2) , P < 0·001), body fat mass (coefficient = 0·948 kg, P < 0·001) and percentage body fat (coefficient = 0·759%, P < 0·01). An instrumental variable (IV) regression model, using BMI as the intermediate phenotype, suggested that FTO was a strong IV. Also, the FTO-BMI polymorphism was significantly associated with total hip and femoral neck BMD but was not correlated with total spine BMD, with estimated correlation coefficients of 0·0189 (95% CI: 0·0046, 0·0332), 0·0149 (95% CI: 0·0030, 0·0268) and 0·0025 (95% CI: -0·0131, 0·0136) g/cm(2) , respectively. The variances of BMDs explained by the FTO-BMI were 19·0%, 21·3% and 1·1%, respectively. Similar trends were also observed for the FTO-body fat mass and FTO-percentage body fat correlations. CONCLUSIONS: Mendelian randomization analysis suggests that adiposity might be causally related to BMD at the femur but not at the spine.

A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI.

Evidence that physical activity (PA) modulates the association between the fat mass and obesity-associated gene (FTO) and BMI is emerging; however, information about dietary factors modulating this association is scarce. We investigated whether fat and carbohydrate intake modified the association of FTO gene variation with BMI in two populations, including participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1069) and in the Boston Puerto Rican Health (BPRHS) study (n = 1094). We assessed energy, nutrient intake, and PA using validated questionnaires. Genetic variability at the FTO locus was characterized by polymorphisms rs9939609 (in the GOLDN) and rs1121980 (in the GOLDN and BPRHS). We found significant interactions between PA and FTO on BMI in the GOLDN but not in the BPRHS. We found a significant interaction between SFA intake and FTO on BMI, which was stronger than that of total fat and was present in both populations (P-interaction = 0.007 in the GOLDN and P-interaction = 0.014 in BPRHS for categorical; and P-interaction = 0.028 in the GOLDN and P-interaction = 0.041 in BPRHS for continuous SFA). Thus, homozygous participants for the FTO-risk allele had a higher mean BMI than the other genotypes only when they had a high-SFA intake (above the population mean: 29.7 ± 0.7 vs. 28.1 ± 0.5 kg/m²; P = 0.037 in the GOLDN and 33.6. ± 0.8 vs. 31.2 ± 0.4 kg/m²; P = 0.006 in BPRHS). No associations with BMI were found at lower SFA intakes. We found no significant interactions with carbohydrate intake. In conclusion, SFA intake modulates the association between FTO and BMI in American populations.

MAT1A variants are associated with hypertension, stroke, and markers of DNA damage and are modulated by plasma vitamin B-6 and folate.

BACKGROUND: The S-adenosylmethionine synthetase type 1 (MAT1A) gene encodes a key enzyme in one-carbon nutrient metabolism. OBJECTIVE: This study aimed to determine the association of MAT1A variants with homocysteine, DNA damage, and cardiovascular disease (CVD). DESIGN: Eight variants of MAT1A were examined for associations with hypertension, stroke, CVD, homocysteine, and DNA damage in 1006 participants of the Boston Puerto Rican Health Study. Two variants were replicated in 1147 participants of the Nutrition, Aging, and Memory in Elders Study. RESULTS: Two variants and haplotypes were strongly associated with hypertension and stroke, independent of methylenetetrahydrofolate reductase (MTHFR) variants. Homozygotes of the MAT1A d18777A (rs3851059) allele had a significantly greater likelihood of stroke (odds ratio: 4.30; 95% CI: 1.34, 12.19; P = 0.006), whereas 3U1510A (rs7087728) homozygotes had a lower likelihood of hypertension (odds ratio: 0.67; 95% CI: 0.48, 0.95; P = 0.022) and stroke (odds ratio: 0.35; 95% CI: 0.15, 0.82; P = 0.015). A similar trend of association was observed in a second elderly population. Furthermore, strong interactions between MAT1A genotypes and vitamin B-6 status were found. Carriers of the nonrisk allele 3U1510A had a lower 8-hydroxydeoxyguanosine concentration--a biomarker of oxidative DNA damage--when plasma vitamin B-6 was high, whereas homozygotes for the risk-allele 3U1510G had higher 8-hydroxydeoxyguanosine concentrations, regardless of vitamin B-6 status. CONCLUSIONS: MAT1A variants were strongly associated with hypertension and stroke. Improving folate and vitamin B-6 status might decrease the CVD risk of only a subset of the population, depending on genotype. These findings suggest that impairments in methylation activity, independent of homocysteine, have an effect on CVD risk.

TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.

BACKGROUND: Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate. METHODS: Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 +/- 16 y) were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes. RESULTS: Under the additive or dominant model, there were no significant differences (P > 0.05) in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-alpha and MCP-1) across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (P < 0.05) post-fenofibrate concentrations of MCP-1 in the recessive model. No other significant associations were detected. CONCLUSION: Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.

ADIPOQ polymorphisms, monounsaturated fatty acids, and obesity risk: the GOLDN study.

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single-nucleotide polymorphisms (SNPs), -11377C>G and -11391G>A, on metabolic-related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the -11391A allele (P = 0.001) but lower for the -11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the -11391G>A SNP. Carriers of the -11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the -11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P-interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (> or =13% of energy intake), -11391A carriers had lower BMI (27.1 kg/m(2) for GA+AA vs. 29.1 kg/m(2) for GG, P = 0.002) and decreased obesity risk (odds ratio for -11391A = 0.52, 95% confidence interval (CI); 0.28-0.96; P = 0.031). However, we did not detect genotype-related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the -11391G>A SNPs and obesity-related traits and the potential to moderate such effects using dietary modification.