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ObjectiveFew epidemiological studies have investigated the associations between calcium, magnesium, and phosphorus intake and pancreatic cancer. We examined these associations in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.MethodsDiet was assessed using the Dietary Questionnaire (DQX) at baseline in the intervention arm and the Dietary History Questionnaire (DHQ) in 1999 or around the third anniversary of randomization in both the intervention and control arms. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer occurred from 58,477 participants who completed DQX; 380 cases arose from 101,622 participants who responded to DHQ over a median follow-up of 8.9 years. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsTotal calcium intake was inversely associated with pancreatic cancer [HR (95% CI) for the fourth vs. the first quartiles in the DHQ cohort: 0.67 (0.47, 0.96); p-trend: 0.035]. An inverse association was also observed for total magnesium intake [HR (95% CI) for the fourth vs. the first quartiles in the DQX cohort: 0.61 (0.37, 1.00); p-trend: 0.023]. Reduced risk associated with total calcium intake was confined to subjects with a high fat intake (>73 g/day) in the DHQ cohort (p-interaction: 0.16).ConclusionsThere was not a significant association between dietary phosphorus intake and pancreatic cancer risk in both cohorts. Total intake of calcium and magnesium are associated with a lower pancreatic cancer risk. The effect of total calcium intake was modified by fat intake.

Background Between 30% and 80% of survivors of critical illness experience cognitive impairment, but the underlying mechanisms remain unknown. Objective To determine whether intensive care unit (ICU) delirium biomarkers align with the National Institute on Aging–Alzheimer’s Association (NIA-AA) research framework for diagnostic biomarkers for Alzheimer disease and other related dementias (ADRD). Methods Ovid MEDLINE, PsycInfo, Embase, and the Cochrane Library were systematically searched for articles published between January 1, 2000, and February 20, 2020, on the relationship between delirium and biomarkers listed in the NIA-AA framework. Only studies that addressed delirium in the ICU setting and fluid biomarkers were included in these analyses. Results Of 61 256 records screened, 38 studies met inclusion criteria, 8 of which were suitable for meta-analysis. In pooled analysis, significant associations were found between ICU delirium and amyloid β-peptide 1-40 (standard mean difference [SMD], 0.42; 95% CI, 0.09-0.75), interleukin (IL)-1 receptor antagonist (SMD, 0.58; 95% CI, 0.21-0.94), and IL-6 (SMD, 0.31; 95% CI, 0.06-0.56). No significant association was observed in pooled analyses between ICU delirium and the other biomarkers. Few studies have examined ICU delirium and pathologic tau or neurodegeneration biomarkers. Conclusions Inflammatory biomarkers and amyloid β are associated with ICU delirium and point to potential overlapping mechanisms between delirium and ADRD. Critical care providers should consider integrating diagnostic approaches used in ADRD in their assessment of post–ICU cognitive dysfunction.

Purpose To evaluate clinical periodontal status and microbiologic pathogens in patients with chronic obstructive pulmonary disease (COPD) and periodontitis. Patients and Methods We conducted a case-control study of 60 periodontitis patients with COPD (case group) and 60 periodontitis patients with normal pulmonary function (control group). Their periodontal status and respiratory function were clinically examined. Real-time polymerase chain reaction assays were used to measure five dental pathogens and four respiratory pathogens in subgingival dental plaque. Spearman's rank correlation coefficients (r2) were calculated to assess correlations of pathogens. Principal component analysis (PCA) was employed to assess the similarity of bacterial diversity between the two groups. Logistic regression was performed to examine the associations of periodontal variables and pathogens with COPD risk. Results COPD patients had fewer remaining teeth, higher plaque index (PLI), and more severe site percentages of clinical attachment level (CAL) than the controls. Although COPD patients tended to have relatively higher ranked means of Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, and Haemophilus influenza than control participants, the differences were not significant. Some periodontal pathogens and respiratory pathogens were positively correlated with each other (r2 =0.29 to 0.47, all P < 0.05). The PCA graph showed that the distributions of pathogens were more dispersed but less discriminated in the COPD group than those in the control group. PLI (P = 0.045) and CAL ≥ 5mm site percentages (P = 0.01) were significantly associated with an increased risk of COPD, while pathogens were not associated with COPD. Conclusion Our results from this study do not indicate periodontal pathogens as potential predictors of COPD risk, despite significantly poor periodontal status associated with COPD.

BACKGROUND: Concentrations of 25-hydroxyvitamin D [25(OH)D] tend to be lower in African Americans than in non-Hispanic whites, but whether adding information on parathyroid hormone (PTH) can help explain the higher cardiometabolic risk among African Americans is unknown. OBJECTIVES: This study examined race (black/white)-specific independent and joint associations of 25(OH)D and PTH with cardiometabolic biomarkers including high-sensitivity C-reactive protein (hs-CRP), estimated glomerular filtration rate (eGFR), and homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). METHODS: Among 1500 white and 1300 black postmenopausal women without cardiovascular disease from the Women's Health Initiative Observational Study, a weighted linear regression analysis and a novel penalized spline-based semiparametric model with contour plots, accounting for possible nonlinear relations and interactions simultaneously, were used to investigate the race-specific independent and joint associations of 25(OH)D and PTH with each biomarker. RESULTS: Black women had lower concentrations of 25(OH)D and higher PTH, HOMA-IR, HOMA-B, hs-CRP, and eGFR than white women (all P values

To examine barriers to weight management among firefighters.Health risk data collected on 2373 overweight firefighters were used for this cross-sectional study. Barriers to weight management were the dependent variables and demographic characteristics, readiness for change, and health risk factors were the correlates in the multivariate-adjusted logistic models.Overweight firefighters who were ready to begin a weight management program were more likely to identify "lack of knowledge about weight management," "lack of access to exercise opportunities," and "eating helps me cope with stress" and report a greater number of barriers toward weight management. Older firefighters were less likely to identify or report one or more barriers to weight management.Understanding barriers, readiness for change, and age may be useful in planning interventions to help firefighters better manage their weight.

Background/objectives There is evidence of black–white differences in vitamin D status and cardiometabolic health. This study aimed to further evaluate the joint associations of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) with risks of diabetes and related cardiometabolic comorbidities among white and black women. Subjects/methods We cross-sectionally and prospectively analyzed data from 1850 black and 3000 white postmenopausal women without cardiovascular disease or dialysis at baseline from the Women’s Health Initiative—Observational Study. Weighted Cox proportional hazards analyses and weighted logistic regression models were used to examine the joint associations of 25(OH)D and PTH with incident diabetes and prevalence of other diabetes-related cardiometabolic comorbidities (including CKD, hypertension, or obesity). Results We identified 3322 cases of obesity (n = 1629), hypertension (n = 2759), or CKD (n = 318) at baseline and 453 incident cases of diabetes during 11 years of follow-up. Cross-sectionally, lower 25(OH)D and higher PTH were independently associated with higher prevalence of hypertension [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.72–0.87 and OR = 1.55; 95% CI: 1.39–1.73] among white women only. When stratified by diabetes status, compared to women with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L (65 pg/mL), women who did not have diabetes with vitamin D deficiency (6.89 pmol/L) had higher prevalence of CKD, hypertension, or obesity (OR = 4.23; 95% CI: 2.90–6.18) than women who had diabetes (OR = 1.89; 95% CI: 0.96–3.71). Prospectively, lower 25(OH)D was associated with lower diabetes incidence [hazard ratio (HR) = 0.73; 95% CI: 0.62–0.86] in white women. Jointly, compared to the group with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L, white women with 25(OH)D deficiency ( Conclusions Low 25(OH)D and high PTH were jointly associated with increased risk of diabetes among white women only. Their joint associations with high prevalence of CKD, hypertension, and obesity were more pronounced among women without diabetes.

BACKGROUND: Non-melanoma skin cancer (NMSC) incidence has been dramatically increasing worldwide. Psoralen, a known photocarcinogen, is naturally abundant in citrus products, leading to the hypothesis that high citrus consumption may increase NMSC risk. METHODS: We fitted age- and multivariable-adjusted logistic regression models to evaluate the association between citrus consumption and NMSC risk among 197,372 UKBB participants. A total of 9,613 NMSC cases were identified using international Classification of Disease 10 codes. Citrus consumption data were collected via five rounds of 24-hour recall questionnaires. RESULTS: We found no association between high total citrus consumption and NMSC risk, although a slightly elevated NMSC risk was observed among participants who consumed >0 to half a serving of total citrus per day (OR [95% CI] = 1.08 [1.01-1.16]). There was no association between individual citrus products and NMSC risk. CONCLUSION: High citrus consumption was not associated with an increased risk of NMSC in our UKBB sample. Further studies are needed to clarify these associations.

Background: This study examined sociodemographic factors, cisplatin-related adverse health outcomes (AHO), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in testicular cancer survivors (TCS). Methods: A total of 1,802 TCS who completed cisplatin-based chemotherapy ≥12 months previously completed questionnaires regarding sociodemographic features and cisplatin-related AHOs [hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), and kidney disease]. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. No cisplatin-related AHOs were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. In the multivariable model, higher CBMPt scores were significantly associated with medication use for anxiety and/or depression (P < 0.0001). In addition, tinnitus (P = 0.0009), PSN (P = 0.02), and having health insurance (P = 0.05) were significantly associated with greater use of these medications, whereas being employed (P = 0.0005) and vigorous physical activity (P = 0.01) were significantly associated with diminished use. Conclusions: TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression, and conversely, those who were employed and physically active tended to have reduced use of these medications. Impact: Healthcare providers should encourage TCS to increase physical activity to improve both physical and mental health. Rehabilitation programs should assess work-related skills and provide career development counseling/training.

Metabolomics is improving the understanding of the mechanisms of the health effects of diet. Previous research has identified several metabolites associated with the Mediterranean Diet (MedDiet), but knowledge about longitudinal changes in metabolic biomarkers after a MedDiet intervention is scarce. A subsample of 48 firefighters from a cluster-randomized trial at Indianapolis fire stations was randomly selected for the metabolomics study at 12 months of follow up (time point 1), where Group 1 (n = 24) continued for another 6 months in a self-sustained MedDiet intervention, and Group 2 (n = 24), the control group at that time, started with an active MedDiet intervention for 6 months (time point 2). A total of 225 metabolites were assessed at the two time points by using a targeted NMR platform. The MedDiet score improved slightly but changes were non-significant (intervention: 24.2 vs. 26.0 points and control group: 26.1 vs. 26.5 points). The MedDiet intervention led to favorable changes in biomarkers related to lipid metabolism, including lower LDL-C, ApoB/ApoA1 ratio, remnant cholesterol, M-VLDL-CE; and higher HDL-C, and better lipoprotein composition. This MedDiet intervention induces only modest changes in adherence to the MedDiet and consequently in metabolic biomarkers. Further research should confirm these results based on larger study samples in workplace interventions with powerful study designs., This research was funded by EMW-2014-FP-00612, US Department of Homeland Security, a Ohio University OURC grant and a CHSP Research Innovation grant, and the 2018 Southeast Center for Integrated Metabolomics Pilot & Feasibility Project. M.S.-P. holds a Ramón y Cajal contract (RYC-2018-025069-I) from the Ministry of Science, Innovation and Universities and FEDER/FSE and FIS grant PI20/00896

OBJECTIVES: The roles of maternal lipidomic profile in fetal growth are rarely studied. This study aims to examine the association of lipidomic profiles over pregnancy with birth weight (BW), neonatal sum of skinfolds (SS) and length, and risks of large- and small-for-gestational-age (LGA, SGA). METHODS: Lipidome analyses were performed among 321 pregnant women from the NICHD Fetal Growth Study-Singletons in the plasma collected at gestational weeks 10–14, 15–26 (fasting), 23–31 and 33–39, using untargeted liquid chromatography-mass spectrometry (LC-MS). The associations of neonatal outcomes with 328 annotated lipid metabolites and 6–9 lipid networks constructed using weighted correlation network analysis were assessed using linear mixed-effects models adjusting for age, race, pre-pregnancy BMI, gestational age of blood collection, and infant sex. False discovery rate (FDR)

Objective: The oral microbiota plays a key part in the initial colonization by pathogens and the chronic inflammatory reaction of the host. We measured variations in the salivary microbiota and evaluated their potential associations with periodontitis and chronic obstructive pulmonary disease (COPD).Methods: We investigated the salivary microbiota of patients with COPD and periodontitis (n = 21) compared with that in patients with periodontitis alone (n = 36) and with healthy controls (HCs; n = 14), using pyrosequencing of polymerase chain reaction-amplified 16s rRNA genes.Results: Bacterial richness and diversity were significantly higher in patients suffering from COPD, and the bacterial family Lachnospiraceae was observed frequently only among patients with COPD and periodontitis. Veillonella, Rothia, Actinomyces, and Fusobacterium were the core bacterial genera that showed significant differences among patients with coincident COPD and periodontitis, patients with periodontitis alone, and HCs (p < 0.05). Veillonella, Rothia, and Actinomyces were observed much more frequently in patients with COPD and periodontitis, compared with that in HCs. All tested populations were divided into subgroups based on sex, smoking, or periodontitis index. In the subgroup with a bleeding index >2, Rothia was significantly different in periodontitis with and without COPD groups compared with HCs. In the subgroup with a plaque index >2.5, Rothia and Veillonella showed significant differences in periodontitis with and without COPD groups compared with HCs.Conclusion: Variations in salivary microbiota may be associated with COPD and periodontitis.

Few studies have examined the associations of serum magnesium (Mg) concentrations with total and cause-specific mortality in a nationally representative sample of US adults. We investigate the dose-response relationships of baseline serum Mg concentrations with risk of mortalities in a large, nationally representative sample of US adults.We analyzed prospective data of 14,353 participants aged 25-74 years with measures of serum Mg concentrations at baseline (1971-1975) from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS). Mortality data was linked through December 31, 2011. We estimated the mortality hazard ratios (HRs), for participants within serum Mg categories of0.7, 0.7-0.74, 0.75-0.79, 0.8-0.89 (referent), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L using weighted multivariate-adjusted Cox proportional hazards models.During a median follow-up of 28.6 years, 9012 deaths occurred, including 3959 CVD deaths, 1923 cancer deaths, and 708 stroke deaths. The multivariate-adjusted HRs (95% CIs) of all-cause mortality across increasing categories of Mg were 1.34 (1.02, 1.77), 0.94 (0.75, 1.18), 1.08 (0.97, 1.19), 1.00 (referent), 1.05 (0.95, 1.16), 0.96 (0.79, 1.15), and 0.98 (0.76, 1.26). Similar trends were observed for cancer (HRs for serum Mg 0.7: 1.39, 95% CI: 0.83, 2.32) and CVD mortality (HRs for serum Mg 0.7: 1.28, 95% CI: 0.81, 2.02) but were not statistically significant. An elevated risk for stroke mortality was observed among participants with serum Mg 0.70 mmol/L (HR: 2.55, 95% CI: 1.18, 5.48).Very low serum Mg concentrations were significantly associated with an increased risk of all-cause mortality in US adults.

Although metabolic syndrome (MetS) is a prognostic factor for cancer occurrence, the association of MetS and cancer mortality remains unclear. The purpose of this study was to evaluate whether MetS, components of MetS and C-reactive protein (CRP) are associated with cancer mortality in women. A total of 400 cancer deaths, with 140 deaths from obesity-linked-cancers (OLCas), [breast (BCa), colorectal, pancreatic and endometrial], linked through the National Death Index, were identified from 10,104 eligible subjects aged ≥18 years. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for cancer mortality. MetS was associated with increased deaths for total-cancer [HR=1.33, 95% confidence interval (CI) 1.04-1.70] and BCa [HR=2.1, 95% CI, 1.09-4.11]. The risk of total-cancer [HR=1.7, 95% CI, 1.12-2.68], OLCas [HR=2.1, 95% CI, 1.00-4.37] and BCa [HR=3.8, 95% CI, 1.34-10.91] mortality was highest for women with all MetS components abnormal, compared to those without MetS. Linear associations of blood-pressure [HR=2.5, 1.02-6.12, Quartile (Q) 4 vs Q1, p-trend=0.004] and blood-glucose [HR=2.2, 1.04-4.60, Q4 vs Q1, p-trend=0.04] with total-OLCas mortality were observed. A three-fold increased risk of BCa mortality was observed for women with enlarged waist circumference, ≥100.9cm, [HR=3.5, 1.14-10.51, p-trend=0.008] and in those with increased blood glucose, ≥101mg/dL, [HR=3.2, 1.11-9.20, p-trend=0.03] compared to those in Q1. None of the components of MetS were associated with total-cancer mortality. CRP was not associated with cancer mortality. In conclusion, MetS is associated with total-cancer and breast-cancer mortality, with waist circumference, blood pressure and blood glucose as independent predictors of OLCas and BCa mortality. This article is protected by copyright. All rights reserved.

Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta‐analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least‐squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever‐users of pioglitazone versus never‐users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time‐ (P = 0.003) and dose‐dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner. Patients with long‐term and high‐dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

Purpose Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta-analysis of observational studies. Methods We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blocking agents (β-blockers), and calcium channel blockers (CCBs). Random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Results Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01-1.20) and SCC (OR, 1.40; 95% CI, 1.19-1.66). Use of β-blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with β-blockers was 1.09 (95% CI, 1.04-1.15) and with CCBs was 1.15 (95% CI, 1.09-1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39-0.71) and SCC (OR, 0.58; 95% CI, 0.42-0.80) in high-risk individuals. Conclusions Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high-risk individuals. β-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.

Background Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the effect of vitamin D intake, either from the diet or from supplements, on the development of gestational diabetes mellitus (GDM) remains unclear. We prospectively examined the association of prepregnancy habitual intake of vitamin D from diet and supplements with the risk of incident GDM in a well-established cohort. Methods The present study was performed on 21 356 singleton pregnancies from 15 225 women in the Nurses’ Health Study II cohort. Diet information, including vitamin D intake from food sources and supplements, was assessed in 1991 and every 4 years thereafter by validated food frequency questionnaires. Log-binomial models with generalized estimating equations were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results During 10 years of follow-up, 865 incident GDM cases were documented. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1–399, and ≥400 IU/day were 1.00 (reference), 0.80 (0.67–0.96), and 0.71 (0.56–0.90), respectively (Ptrend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Conclusions Prepregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.

People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver diseases. We evaluated the association between total magnesium intake and mortality due to liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver disease at borderline significance (P = 0.05). In fully-adjusted analyses, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P > 0.05), inverse associations between magnesium intake and liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.

Background Sex hormones may play important roles in sex-specific biological aging. We specifically examined the associations between circulating concentrations of sex hormones and leukocyte telomere length (TL). Methods We conducted a cross-sectional study of 1124 black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Concentrations of estradiol and testosterone were measured using electrochemiluminescence immunoassays. TL was measured using quantitative PCR. Results Women included in the study were 50 to 79 years of age. Levels of estradiol were not significantly associated with TL in this sample of women. The associations between total and free testosterone and TL differed by race/ethnicity (P for interaction = 0.03 for total testosterone and 0.05 for free testosterone). Total and free testosterone concentrations were not associated with TL in black and Hispanic women, whereas in Asian/Pacific Islanders, their concentrations were inversely associated with TL (P-trend = 0.003 for both). These associations appeared robust in multiple subgroup analysis and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islanders, doubling of serum free testosterone concentration was associated with 202 bp shorter TL (95% CI, 51 to 353 bp), and doubling of total testosterone concentration was associated with 203 bp shorter TL (95% CI, 50 to 355 bp). Conclusions Serum concentration of estradiol was not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone levels were inversely associated with TL in Asian/Pacific Islander women but not in black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relations. The significant findings of the study This study elucidates the potential roles of sex hormones in biological aging, and identified that total and free testosterone levels were inversely associated with telomere length in Asian/Pacific Islander women but not in black and Hispanic women. The study adds The findings of this study suggest that Asian/Pacific Islander women may be susceptible to the potential detrimental effects of high testosterone level on biologic aging.

Background Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relation between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies. Methods Among postmenopausal women with available SHBG measurements at baseline (n = 11,159) in the Women's Health Initiative, we conducted a comprehensive assessment of total dietary carbohydrates, glycemic load (GL), glycemic index (GI), fiber, sugar, and various carbohydrate-abundant foods in relation to circulating SHBG using multiple linear regressions adjusting for potential covariates. Linear trend was tested across quartiles of dietary variables. We used Benjamini and Hochberg's procedure in calculating the false discovery rate (FDR) for multiple comparisons. Results Higher dietary GL based on total and available carbohydrates, dietary GI based on total and available carbohydrates, and higher intake of sugar and sugar sweetened beverages were associated with lower concentrations of circulating SHBG (all Ptrend

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients. Methods This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0–24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13–24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24. Discussion This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients. Trial registration ClinicalTrials.gov, NCT03337035. Registered 8 November 2017.

Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

This study aimed to examine the prevalence and associated factors of lupus among adults in the United States. This study included 20,045 participants aged 17 years and older from the Third National Health and Nutritional Examination Survey (NHANES III) from 1988 to 1994. Their lupus status was determined by survey questions in terms of a clinician's diagnosis. Demographics and laboratory test results of all participants were collected, including biochemistry, nutrition, and antibody biomarkers. Continuous variables were compared between cases with reported lupus and non-case controls by t-test, while the Chi-square test was used for categorical variables. Weighted multivariate-adjusted logistic regression models after adjustment of covariates were used to identify associated factors of lupus risk. Of 20,045 participants, 40 people who self-reported a lupus diagnosis were identified, giving a prevalence of 241 per 100,000 (n = 40; 95% confidence interval: 133–349 per 100,000). Many factors differed significantly between lupus cases and controls. Multivariate logistic regression analysis further identified previous and current smoking along with elevated serum levels of chloride, globulin, lactate dehydrogenase, uric acid, cholesterol, and lutein or zeaxanthin as risk factors; while protective factors against lupus included non-white race, obesity, elevated serum levels of bicarbonate, creatinine, total calcium, and vitamin B12, as well as elevated urinary albumin and iodine. Our nationwide data indicate that race, obesity, cigarette smoking, and certain biomarkers such as serum lutein or zeaxanthin, calcium, and cholesterol may be associated with the development or progression of lupus, although these findings need to be confirmed in further prospective investigations.

Background Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10–17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10–24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10–10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10–10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10–8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.

Introduction Large interdialytic weight gain (IDWG) is associated with increased morbidity and mortality in chronic hemodialysis patients. Over 50% of patients at our inner city tertiary academic center dialysis unit had IDWG and target weights (TW) above goal. We conducted an open-label nonrandomized study to explore the effects of an individualized dialysate sodium (DNa) prescription using Na gradients in patients at high risk for large IDWG. Thirty-three patients receiving chronic hemodialysis received individualized DNa prescriptions with a DNa bath of 0 to -2 meq/L below their serum Na level in the intervention group, while patients in the control group were prescribed the standard dialysate Na at 138 mmol/L. Serum Na level, predialysis SBP, symptomatic hypotensive episodes, and %hemodialysis treatments with large IDWG (%TxAIDWG) and above TW(%TxATW) were recorded before and three months after the intervention. We used student t tests to compare continuous variables and Chi-square tests to compare binary variables between the groups at baseline and after the intervention. Age- and sex-adjusted linear regression models were also constructed to assess the differences in each continuous outcome between the groups. Multivariable logistic regression models were conducted by modeling IDWG decrease and above estimated-dry-weight (EDW) decrease as binary dependent variables with adjustment for age, sex, and EDW change. Findings Patients with individualized DNa concentrations had 3.6 times greater odds of having lower IDWG than those with standard dialysate Na concentration. This significant association remained after adjustment for age, sex, and changes in EDW (OR: 3.63; 95% CI, 1.03-12.9). There was no difference in predialysis BP or symptomatic hypotensive episodes between the two groups. Discussion Individualized DNa prescriptions appeared to be well tolerated and may be effective for optimal fluid management in high-risk hemodialysis patients.

Objective: Prolactin and progesterone are implicated in glucose homeostasis in and outside of pregnancy. However, their associations with gestational diabetes (GDM) risk were not well-understood. This study investigates this question in a prospective and longitudinal cohort. Methods: This is a nested case-control study of 107 incident GDM cases and 214 matched non-GDM controls within the NICHD Fetal Growth Studies-Singleton Cohort. Blood samples were collected at gestational weeks 10-14, 15-26, 23-31, and 33-39. The odds ratios (OR) of GDM were estimated using conditional logistic regression. The longitudinal changes in prolactin and progesterone were estimated using linear mixed-effects models. Results: Compared to controls, cases have significantly higher prolactin levels at weeks 10-14 (median: 50.4 vs. 42.1 ng/mL), and significantly lower progesterone levels at weeks 10-14 (median: 109.4 vs. 126.5 nmol/L). Prolactin levels at weeks 10-14 were significantly and positively associated with GDM risk; the adjusted ORs across increasing quartiles were 1.00, 1.13, 1.80, 2.33 (p-trend = 0.02). A similar but slightly attenuated association was observed at weeks 15-26 (p-trend = 0.05). Progesterone was not associated with GDM risk at either time points. Longitudinal changes in prolactin and progesterone between the first two visits were not associated with GDM risk. In addition, prolactin was significantly and positively associated with insulin and C-peptide levels at weeks 10-14, and significantly and inversely associated with C-peptide levels at weeks 15-26; progesterone was significantly and inversely associated with glucose and insulin levels. Conclusions: This study provided the first prospective evidence of a positive association between prolactin levels in early pregnancy and GDM risk.

Collecting dietary intake data is associated with challenges due to the subjective nature of self&ndash, administered instruments. Biomarkers may objectively estimate the consumption of specific dietary items or help assess compliance in dietary intervention studies. Our aim was to use a panel of plasma and urine biomarkers to assess the validity of self-reported dietary intake using a modified Mediterranean Diet Scale (mMDS) among firefighters participating in Feeding America&rsquo, s Bravest (FAB), an MD cluster-randomized controlled trial. In our nested biomarker pilot study, participants were randomly selected from both the MD intervention group (n = 24) and the control group (n = 24) after 12-months of dietary intervention. At baseline data collection for the pilot study (t = 12-months of FAB), participants in the control group crossed-over to receive the MD intervention (active intervention) for 6-months. Participants in the intervention group continued in a self-sustained continuation phase (SSP) of the intervention. Food frequency questionnaires (FFQ), 13-item-mMDS questionnaires, 40 plasma fatty acids, inflammatory biomarkers and urinary hydroxytyrosol and tyrosol were analyzed at both time points. Spearman&rsquo, s correlation, t-tests and linear regression coefficients were calculated using SAS software. Overall, the mMDS derived from the FFQ was highly correlated with the specific 13-domain-mMDS (r = 0.74). The concordance between the two questionnaires for low and high adherence to MD was high for all the participants in the parent trial (&kappa, = 0.76). After 6 months of intervention in the pilot study, plasma saturated fatty acid decreased in both groups (active intervention: &minus, 1.3 &plusmn, 1.7, p = 0.002, SSP: &minus, 1.12 &plusmn, 1.90, p = 0.014) and oleic acid improved in the SSP (p = 0.013). Intake of olive oil was positively associated with plasma omega-3 (p = 0.004) and negatively with TNF-&alpha, (p &lt, 0.001) at baseline. Choosing olive oil as a type of fat was also associated with higher levels of plasma omega-3 (p = 0.019) at baseline and lower TNF-&alpha, (p = 0.023) at follow up. Intake of red and processed meats were associated with lower serum omega-3 (p = 0.04) and fish consumption was associated with lower IL-6 at baseline (p = 0.022). The overall mMDS was associated with an increase in plasma omega-3 (p = 0.021). Good correlation was found between nutrient intake from the FFQ and the corresponding plasma biomarkers (omega-3, EPA and DHA). In this MD randomized controlled trial, some key plasma biomarkers were significantly associated with key MD diet components and the overall mMDS supporting the validity of the mMDS questionnaire as well as compliance with the intervention.

OBJECTIVES This trial aimed to evaluate the efficacy and safety of vitamin D supplementation on the residual moderate and deep pockets following nonsurgical periodontal therapy. BACKGROUND Vitamin D supplementation has potential effects on periodontitis, but current evidence remains inconclusive. METHODS After 3 months of nonsurgical periodontal treatment, 360 patients with moderate or severe periodontitis were randomly assigned to 2000 international unit (IU)/d vitamin D3, 1000 IU/d vitamin D3, or placebo. Clinical periodontal examinations, including probing depth (PD), bleeding index (BI), plaque index (PLI), attachment loss (AL), and alveolar crest height (ACH), were performed at baseline and after 3 months of intervention. RESULTS There was a slight but significant decrease in AL and PD in both vitamin D groups compared with placebo group for moderate and deep pockets. About 2000 IU/d vitamin D3 group, 1000 IU/d vitamin D3 group, and placebo group all decreased the AL for both moderate pockets (-0.4 mm vs -0.4 mm vs -0.3 mm) and deep pockets (-1.1 mm vs -1.1 mm vs -1.0 mm) (all P

Background Multiple genetic and environmental factors contribute to the individual‐level heterogeneity in stroke. This study aimed to assess how the genetic interactions confer risk of stroke. Methods In a Chinese case‐control study including 1,405 strokes and 1,263 controls who were followed up (range, 0.1–6.0 years), eight genes, including apolipoprotein(a) (APOA1), methylenetetrahydrofolate reductase (MTHFR), vitamin K epoxide reductase complex subunit 1 (VKORC1), arachidonate 5‐lipoxygenase‐activating protein (ALOX5AP), NOTCH3, chromosome 9p21.3(Chr.9p21.3), vascular endothelial growth factor (VEGFA), and kinase insert domain‐containing receptor (KDR), were analyzed for interactions by the generalized multifactor dimensionality reduction method and validated by the multivariate logistic regression models. The genetic associations with carotid artery intima‐media thickness (IMT) were examined. Results The interaction of VKORC1 and Chr.9p21.3 was identified for stroke and its worse prognosis, and subjects having the VKORC1 rs2359612C and Chr.9p21.3 rs10757274G alleles had higher risks for stroke (OR = 1.83, 95% CI = 1.32–2.52) as well as for stroke recurrence (HR = 1.84, 95% CI = 1.24–2.73), cardiovascular events (HR = 1.65, 95% CI = 1.15–2.38), and cardiovascular mortality (HR = 2.16, 95% CI = 1.24–3.79). Supporting, they were associated with higher IMT. Hypertension or physical inactivity increased the risk effect. The interaction of VEGFA rs833061C and KDR rs2305948T was identified for hemorrhagic stroke. Conclusions Our findings identified two novel genetic interactions of VKORC1 and Chr.9p21.3 and of VEGFA and KDR for risk of stroke and subtypes as well as future stroke prognosis.

Purpose This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM). Methods Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. Results Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence). Conclusions Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.

Purpose Sodium glucose cotransporter 2 (SGLT2) inhibitors are shown to cause small, but significant changes of lipid profiles, we aim to investigate whether such altered lipid profiles can be translated into clinically meaningful changes in dyslipidemia. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with placebo or other oral glucose-lowering drugs in patients with type 2 diabetes mellitus and reported the events of dyslipidemia. A random-effect meta-analysis was performed to calculate the pooled estimates with risk ratio (RR) for dyslipidemia risk and weighted mean difference for lipid profiles with their 95% confidential intervals (CIs). Results Of 2427 studies identified, 15 RCTs involving 7578 patients were included. This meta-analysis found no association between SGLT2 inhibitors and risk of dyslipidemia (RR: 1.13; 95% CI: 0.91-1.40). However, SGLT2 inhibitors were significantly associated with increases in total cholesterol by 0.15 mmol/L, low-density lipoprotein cholesterol by 0.12 mmol/L, and high-density lipoprotein cholesterol by 0.07 mmol/L while they can significantly decrease triglycerides by -0.12 mmol/L compared to controls. Conclusions SGLT2 inhibitors were not associated with increased risk of dyslipidemia. Further trials with longitudinal assessment are needed to assess the effect of SGLT2 inhibitors on trajectories of changes of lipid metabolism.

OBJECTIVES: Plasma profile of acylcarnitines has been suggested to associate with adverse maternal outcomes such as gestational diabetes. However, data on their associations with neonatal outcomes are sparse. Therefore, this study aimed to examine the prospective profile of acylcarnitines across gestation and its association with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SSF), length, and circumferences. METHODS: Among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons cohort, we quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in the plasma at gestational weeks 10–14, 15–26, 23–31 and 33–39, accordingly. We firstly applied a latent-class trajectory approach to identify trajectories of acylcarnitines across gestation, and secondly examined associations of individual acylcarnitine and distinct trajectory groups with neonatal anthropometry using weighted linear models with robust standard errors, adjusting for maternal age, race/ethnicity, education, parity, gestational week of blood collection, and pre-pregnancy body mass index. RESULTS: We identified three distinct trajectory groups of C2, C3 and C4, and two trajectory groups of C5, C10, C5-DC, C8:1, C10:1 and C12, respectively. Newborns of women with nonlinear decline of C12 levels across gestation (5.7%) had significantly smaller BW (−475 g; 95% CI: −942, −6.79 g), BW z-score (−0.39; −0.71, −0.06), and length (−1.38 cm; −2.49, −0.27 cm) than those with persistently stable C12 levels (94.3%). Newborns of women with consistently higher levels of C10 (6.1%) had greater sum of skinfolds (4.91 mm; 0.85, 8.98 mm) than those with lower levels (93.9%) across pregnancy, whereas newborns of women with declining C10:1 levels (12.6%) had larger sum of skinfolds (3.23 mm; 0.19, 6.27 mm) than those with abruptly increasing levels (87.4%). CONCLUSIONS: In conclusion, gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to verify and further explore the potential clinical utility of these findings. FUNDING SOURCES: Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding; American Recovery and Reinvestment Act funding.

5025 Background: Cancer survivors are at increased risk of anxiety and depression that can affect health-related quality of life. There is no study to date that has examined the characteristics of testicular cancer survivors (TCS) taking medications for anxiety or depression since pharmacological interventions are typically reserved for more severe cases of these disorders. In this study, we aimed to examine sociodemographic factors, cisplatin-related adverse health outcomes (AHOs), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in TCS. Methods: A total of 1,802 TCS who completed CBCT ≥12 months previously completed validated questionnaires regarding sociodemographic features and cisplatin-related AHOs (hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), kidney disease). Patients were recognized as users of medications for anxiety and/or depression if they used pharmacological classes of these medications and also indicated that the reason for use was for anxiety or depression. Individual AHOs were graded 0-to-4 based on severity according to NCI Common Terminology Criteria for Adverse Events version 4.03. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. Any grade of HL, tinnitus, PSN, and kidney disease were reported by 37.9%, 39.5%, 55.2%, and 2.4% of 1,802 participants, respectively. No cisplatin-related AHO were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. Higher CBMPt scores were significantly associated with greater medication use for anxiety and/or depression (CBMPt scores of low (OR = 2.96, 95%CI, 1.67-5.24), medium (OR = 3.47, 95%CI, 1.95-6.18), and high (OR = 3.18, 95%CI, 1.22-8.3). A multivariable model including individual AHOs indicated that tinnitus ( P= 0.0009), PSN ( P= 0.02), and having health insurance (OR = 2.15, 95%CI, 1.01-4.56) were associated with significantly greater use of these medications; whereas being employed (OR = 0.39, 95%CI, 0.23-0.66) and vigorous physical activity (OR = 0.63, 95%CI,0.44-0.89) were associated with significantly diminished use. Conclusions: We found that TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression and conversely, those who were employed and physically active tended to have reduced use. These findings deserve further investigation in longitudinal studies. In the interim, healthcare providers should be aware of these associations in formulating survivorship care plans.

5016 Background: Although pure-tone audiometry is the gold standard to evaluate hearing loss (HL), patient-reported outcomes are practically more time and cost effective. However, no data exist on factors associated with discrepancies between patient-reported and audiometrically-defined HL in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT); and few comprehensive assessments of factors associated with audiometrically-defined HL have been conducted. Methods: A total of 1,410 testicular cancer survivors (TCS) ≥6 months post-CBCT completed comprehensive audiometric assessments (0.25-12 kHz) and detailed questionnaires of sociodemographic, clinical, and health behaviors. Audiometrically-defined HL severity was defined using American Speech-Language-Hearing Association (ASHA) criteria. Multivariable multinomial logistic regression identified factors associated with discrepancies (overestimation and underestimation vs. concordance), between patient-reported and audiometrically-defined HL and multivariable ordinal logistic regression evaluated factors associated with the HL severity. Results: Overall, 34.8% of TCS self-reported HL, while 77.8% had audiometrically-defined HL. Among TCS without tinnitus, those with audiometrically-defined HL at only extended high frequencies (EHFs) (10-12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25-8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically-defined HL (8.1%) (OR = 2.48; 95%CI, 1.31-4.68 and OR = 3.49; 95%CL,1.89-6.44, respectively). Older age (OR = 1.09; P< 0.0001), absence of prior noise exposure (OR = 1.40; P= 0.02), and mixed/conductive HL (OR = 2.01; P= 0.0007) were associated with greater underestimation of audiometrically-defined HL severity. Hearing aid use (OR = 0.18; P= 0.003) and higher education ( P= 0.004) were associated with less underestimation of audiometrically-defined HL severity, while tinnitus was associated with greater overestimation ( P< 0.0001). Older age (OR = 1.13; P< 0.0001), cumulative cisplatin dose ( > 300 mg/m2, OR = 1.47; P= 0.0001), and hypertension (OR = 1.80; P= 0.0007) were associated with greater ASHA-defined HL severity, whereas post-graduate education (OR = 0.58; P= 0.005) was associated with less severe HL. Conclusions: Discrepancies between patient-reported and audiometrically-defined HL after CBCT are associated with several factors including age, education, tinnitus, prior noise exposure, use of hearing aids, and conductive HL. Understanding these factors will help clinicians to better interpret self-reported HL as a surrogate for audiometric assessments. For survivors who self-report HL, but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments, should be considered.

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential, however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3–20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks, starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p &lt, 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p &lt, 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.

Aim To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

Background.The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies.Subjects/Methods.We conducted prospective analysis in the Physicians’ Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years’ follow-up.Results.Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06–1.59] for BMI 25–2and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years’ follow-up, resp.).Conclusion.In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up.

Aim To examine the association of cutaneous nevi with Type 2 diabetes risk. Methods We prospectivly examined the associations between nevus count and risk of Type 2 diabetes among 26 240 men (1988–2010) from the Health Professionals Follow-up Study and 67 050 women (1986–2010) from the Nurses’ Health Study. Information on the numbers of cutaneous nevi on arms at baseline and incident cases of Type 2 diabetes was collected using validated questionnaires. Results During 1 879 287 person-years of follow-up, we documented 9040 incident cases of Type 2 diabetes. After adjustment for age, BMI and other diabetes risk factors, greater number of nevi was associated with higher risk of Type 2 diabetes. Multivariable-adjusted hazard ratios for

By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients.We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels. Weighted mean differences (WMD) between each SGLT2 inhibitor and placebo were calculated using a random-effects model. Dose-dependent relationships for each SGLT2 inhibitor were evaluated using meta-regression analysis.Eighteen eligible RCTs, including 15,309 patients and four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated. In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg). Canagliflozin increased serum magnesium in a linear dose-dependent manner (p = 0.10). Serum phosphate was significantly increased by dapagliflozin. Serum sodium appeared to significantly differ by SGLT2 inhibitor type. No significant changes in serum calcium and potassium were observed. Findings were robust after including trials involving patients with chronic kidney disease.SGLT2 inhibitors marginally increased serum magnesium levels in type 2 diabetes patients indicating a drug class effect. Further investigations are required to examine the clinical significance of elevated magnesium levels in individuals with type 2 diabetes.

Aim Given the conflicting evidence of sodium-glucose cotransporter 2 (SGLT2) inhibitors on bone health in patients with type 2 diabetes Mellitus (T2DM), we aimed to evaluate the comparative effects of SGLT2 inhibitors on risk of bone fracture. Methods PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were systematically searched from inception to January 27, 2016 to identify RCTs reporting the outcome of fracture in T2DM patients with the use of SGLT2 inhibitors. A pairwise and network meta-analyses, as well as a cumulative meta-analysis were performed to calculate their odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin, and 13 empagliflozin) involving 30,384 patients with periods of follow-up ranged from 24 to 160 weeks were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture event was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR, 1.15; 95%CI, 0.71 to 1.88), dapagliflozin (OR, 0.68; 95%CI, 0.37 to 1.25), and empagliflozin (OR, 0.93; 95%CI, 0.74 to 1.18) was not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of our null findings of SGLT2 inhibitors. Conclusions Our meta-analysis based on available RCT data does not support the harm effect of SGLT2 inhibitors on fracture, although future safety monitoring from RCT and real-world data with detailed information on bone health is warranted.

Background Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B-100 (apo B-100), and cancer risk have been sparse, to our knowledge. Objectives We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline). Design Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors. Results Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained. Conclusions Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Background: Lifestyle modification and some pharmacological interventions have been proven effective in preventing type 2 diabetes (T2D) in previous primary prevention trials. However, there is controversy regarding their comparative effectiveness because of the lack of head-to-head trials for all possible comparisons among different interventions. Network meta-analysis enables us to simultaneously evaluate the relative effectiveness among all interventions by synthesizing both direct evidence from head-to-head trials and indirect evidence through more than one common comparator while maintaining randomization. Objective: We performed a network meta-analysis of randomized controlled trials (RCTs) to directly and indirectly compare lifestyle modification and five commonly prescribed medications (insulin sensitizers, insulin secretagogues, alpha-glucosidase inhibitors, weight-loss drugs, and renin-angiotensin system blockade), and to rank their relative effectiveness for primary prevention of T2D among adults with prediabetes at enrollment. Methods: We systematically searched PubMed, Embase, and CENTRAL from inception to October 2018 and identified long-term RCTs (follow-up ≥ 1year) that evaluated the interventions for T2D prevention in adults with prediabetes (e.g. impaired fasting glucose and impaired glucose tolerance). A network meta-analysis using the frequentist approaches was conducted to calculate the summary odds ratio (OR) and 95% confidence interval (CI) for each active intervention in comparison with controls (i.e. usual care alone or with placebo or control pills) and rank the effectiveness of these interventions by the surface under the cumulative ranking curve probabilities. Results: Thirty-three RCTs involving 54,910 individuals with prediabetes and 13,189 diabetic cases were included. Network meta-analysis showed that lifestyle modification (OR, 0.53; 95% CI, 0.42 to 0.66), insulin sensitizers (0.44; 0.31 to 0.62), alpha-glucosidase inhibitors (0.60; 0.42 to 0.87), and weight-loss drugs (0.39; 0.23 to 0.66) were significantly associated with decreased risk of incident T2D as compared with the controls. Neither insulin secretagogues (0.80; 0.51 to 1.26) nor renin-angiotensin system blockade (0.93; 0.62 to 1.38) were significantly associated with lower risk of developing T2D. Ranking of these interventions revealed weight-loss drugs being the optimal intervention for preventing T2D (89.5%), followed by insulin sensitizers (84.1%), lifestyle modification (66.7%), and alpha-glucosidase inhibitors (54.4%). Conclusions: Among the four interventions (lifestyle modification, insulin sensitizers, alpha-glucosidase inhibitors, and weight-loss drugs) which showed significant benefits on the primary prevention of T2D, weight-loss drugs seem to be the most effective.

Background Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25‐hydroxy vitamin D (25[ OH ]D) rather than total 25( OH )D may explain apparent racial disparities in cardiovascular disease ( CVD ). We prospectively examined black‐white differences in the associations of total, free, and bioavailable 25( OH )D, vitamin D–binding protein, and parathyroid hormone levels at baseline with incident CVD (including nonfatal myocardial infarction, nonfatal stroke, and CVD death) in postmenopausal women. Methods and Results We conducted a case‐cohort study among 79 705 postmenopausal women, aged 50 to 79 years, who were free of CVD at baseline in the WHI‐OS (Women's Health Initiative Observational Study). A subcohort of 1300 black and 1500 white participants were randomly chosen as controls; a total of 550 black and 1500 white women who developed incident CVD during a mean follow‐up of 11 years were chosen as cases. We directly measured total 25( OH )D, vitamin D–binding protein, albumin, parathyroid hormone, and calculated free and bioavailable 25( OH )D. Weighted Cox proportional hazards models were used to examine their associations with CVD risk. Although vitamin D–binding protein and total, free, and bioavailable 25( OH )D were not significantly associated with CVD risk in black or white women, a significant positive association between parathyroid hormone and CVD risk persisted in white women (hazard ratio comparing the highest quartile with the lowest, 1.37; 95% CI , 1.06–1.77) but not in black women (hazard ratio comparing the highest quartile with the lowest, 1.12; 95% CI, 0.79–1.58), independent of total, free, and bioavailable 25( OH )D or vitamin D–binding protein. Conclusions Circulating levels of vitamin D biomarkers are not related to CVD risk in either white or black women. Higher parathyroid hormone levels may be an independent risk factor for CVD in white women.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Animal studies showed that Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. We thus designed the first clinical trial to test whether supplementation with L. reuteri would improve social behavioral functions in ASD patients; whether there is a synergy between probiotics treatment and exogenous OXT therapy; and whether such OXT pathway-targeted therapies alter the gut-brain axis, including autonomic function, gastrointestinal (GI) health, gut microbial profiles, gut/brain inflammation, and brain activity. Methods/design: This clinical trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0-24 weeks), 60 ASD patients will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the 2nd stage (13-24 weeks) of the study, all participants will also receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be measured via two validated questionnaires, an objective emotional facial matching test, and a new video-based eye tracking test. Secondary outcomes include autonomic function indices, GI function, gut microbiome/short chain fatty acids, brain activity in social response regions via functional magnetic resonance imaging (fMRI), and serum neuroinflammatory/neurotransmitter/neuro-injury biomarkers. All the outcomes will be assessed at baseline, week 12, and week 24. Discussion: This pilot study will provide important empirical data to evaluate potential effects of oral probiotics in improving ASD core symptoms through modulating endogenous OXT, examine the synergistic effects between probiotics and exogenous OXT treatment, and further explore the relationship of OXT with the gut-brain axis in ASD patients. Trial registration: ClinicalTrial.gov, NCT03337035. Registered 8 November 2017, https://clinicaltrials.gov/ct2/show/NCT03337035 Keywords: Autism spectrum disorders; Intranasal; Oxytocin; Probiotics

Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trendn-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms.

Background: Emerging evidence suggests that vitamin D status in pregnancy may be associated with the development of gestational diabetes (GDM). However, the temporal relationship remains unclear due to the lack of prospective data with serial measurements of maternal vitamin D levels. We prospectively examined longitudinal changes in vitamin D biomarkers in relation to subsequent GDM risk. Methods: A nested case-control study of 107 GDM cases and 214 controls (matched on age, race/ethnicity, and gestational week (GW) at blood draw) was conducted within the NICHD Fetal Growth Studies-Singleton Cohort (2009-2013). Plasma concentrations of D2 and D3 25-hydroxyvitamin D (25(OH)D) and vitamin D binding protein were measured at GWs 10-14, 15-26, 23-31, and 33-39; we further calculated total, free, and bioavailable 25(OH)D. Linear mixed-effects models and conditional logistic regression models were used adjusting for confounders. Results: Compared with controls, women who developed GDM appeared to have lower concentrations of total 25(OH)D as early as GWs 10-14 (median: 25.59 vs. 27.46 ng/mL) and had a greater longitudinal increase in total 25(OH)D levels from GWs 10-14 to 15-26 (LS mean difference in log-scale: 0.10 vs. 0.04, p=0.046). We found no linear associations between vitamin D biomarkers at GWs 10-14 or GWs 15-26 and GDM risk. However, vitamin D deficiency ( Conclusions: Our findings suggest that maternal vitamin D deficiency in the first trimester of pregnancy may be implicated in the development of GDM. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for the primary prevention of GDM. Disclosure J. Xia: None. Y. Song: None. S. Rawal: None. J. Wu: None. S. Hinkle: None. M.Y. Tsai: None. C. Zhang: None.

Background: Recent studies have shown that sarcopenia defined as the loss of muscle mass and/or strength was associated with diabetes and independently predicted all-cause mortality in older adults; however, it is unclear whether sarcopenia and diabetes synergistically affect all-cause mortality. Methods: We aimed to prospectively examine joint associations of sarcopenia (defined by either low muscle mass (LMM), low muscle strength (LMS), or both) and diabetes on all-cause mortality in a nationally representative sample of U.S. adults, including 4,449 participants aged 50 years and older from NHANES 1999-2002 with linked mortality data. Weighted multivariable logistic regression models were adjusted for age, sex, race, BMI, smoking, alcohol use, education, leisure time physical activity, sedentary time, and comorbid diseases. Results: Overall, we had 971 with diabetes and 921 with sarcopenia defined by LMM (ALM/BMI), 762 with LMS, 207 with sarcopenia defined by both LMM (ALM/BMI) and LMS. The prevalence of sarcopenia was higher in diabetic than nondiabetic individuals (23.7% vs. 14.6% for LMM, 15.8% vs. 13.8% for LMS, and 4.0% vs. 3.5% for both LMM and LMS). In the joint analyses, diabetic individuals had increased risk of all-cause mortality than those without diabetes or LMM, whether they had LMM (OR=2.79; 95% CI: 1.56-4.98) or not (OR=1.40; 95% CI: 1.02-1.92) (P for joint effect=0.001). LMS was associated with higher risk of all-cause mortality among both diabetic (OR=4.10; 95% CI: 1.59-10.55) and nondiabetic individuals (OR=2.39; 95% CI: 1.77-3.23) (P for joint effect Conclusions: Our results suggest that LMS was independently and strongly associated with elevated risk of all-cause mortality, with additional risk synergistically with diabetes among U.S. older adults. Disclosure J. Xia: None. Y. Song: None.

A slight increase in melanoma risk was observed among sodium-glucose co-transporter-2 (SGLT-2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta-analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT-2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80-5.89; I2 , 0%). Similar results were observed in the subgroup analyses according to the type of SGLT-2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non-melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47-1.07; I2 , 0%), while a significantly decreased risk was observed among trials with duration

We aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM.We searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls.Of 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 μg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified.Adiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipokines with GDM risk.

With increasing diabetes prevalence in the US general population, many nutritional supplements are taken as alternative medicine by diabetic patients. However, serial trends or patterns in their dietary supplement use are unknown. Using the nationally representative data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2014, we evaluated prevalence and trends of use of any supplements, multi-vitamins/multi-minerals (MVMM), individual vitamins, minerals, and non-vitamin, non-mineral supplements. Information on supplement use in the preceding 30 days was collected during the interview over 8 continuous 2-year waves. Analyses were conducted among 6,348 US diabetic adults aged 20 to 85 years (pregnant women excluded) and also stratified by age, race/ethnicity, gender, educational backgrounds, comorbidity status, and comorbidity status. Overall, the prevalence of use of any supplement (52%-59%; P for trend=.09) and that of any mineral (47%-51%; P for trend=.24) seemed stable. Use of MVMM decreased from 36% of reported use in 1999-2000 to 32% in 2013-2014 ( P for trend=.008). Use of any vitamin products increased from 47% to 53% ( P for trend=.04). Use of a few individual supplements including lycopene, vitamin D, and vitamin B12 significantly increased. The trend of supplement use varied by sex and race/ethnicity. In conclusion, among diabetic patients in the United States, use of any dietary supplements or any minerals remained stable, use of MVMM slightly decreased, and use of any vitamins and several individual supplements increased over the past 16 years.