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Background The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. Objectives We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. Methods This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. Results The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). Conclusions Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D. [ABSTRACT FROM AUTHOR]

Background Although low-carbohydrate and low-fat diets are beneficial in short-term metabolic improvement, the associations of these dietary patterns, particularly with different food sources and quality of macronutrients, with mortality remain unclear among people with prediabetes. Objectives We aimed to examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality among individuals with prediabetes. Methods This study included 9793 adults with prediabetes from the NHANES 1999–2014. Mortality status was linked to National Death Index mortality data through 31 December, 2015. Overall, unhealthy, and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate HRs and 95% CIs. Results Higher healthy LCD score was associated with favorable blood glucose, insulin, HOMA-IR, C-reactive protein (CRP), and blood lipids, whereas higher healthy LFD score was associated with lower blood glucose and CRP at baseline (all P -trend < 0.05). During 72,054 person-years of follow-up, 1352 deaths occurred. The multivariate-adjusted HRs (95% CIs) of all-cause mortality per 20-percentile increment in dietary scores were 0.88 (0.80, 0.96) for healthy LCD score (P  = 0.003), 0.85 (0.78, 0.93) for healthy LFD score (P  < 0.001), 1.09 (0.99, 1.21) for unhealthy LCD score (P  = 0.08), and 1.11 (1.00, 1.22) for unhealthy LFD score (P  = 0.05). Isocalorically replacing 3%–5% energy of low-quality carbohydrate or saturated fat with high-quality carbohydrate, plant-based protein, or unsaturated fat was associated with a 14%–37% reduced all-cause mortality. Conclusions Healthy LCD and LFD scores were significantly associated with lower all-cause mortality, whereas unhealthy LCD and LFD scores tended to be associated with higher all-cause mortality, among people with prediabetes. [ABSTRACT FROM AUTHOR]

Background Knowledge of glycemic status may affect dietary intake for subjects with diabetes and prediabetes. Objectives We aimed to determine whether trends of macronutrient intake and dietary quality differed by diagnosis of glycemic status among US adults with diabetes and prediabetes. Methods Data from NHANES 1999–2016 were analyzed. Diagnosed cases were established by self-report, and undiagnosed cases were defined by laboratory criteria (glycated hemoglobin ≥ 5.7%, fasting plasma glucose ≥ 100 mg/dL, or 2-h oral-glucose-tolerance test ≥ 140 mg/dL). A difference-in-differences model was used to compare the temporal trends between the 2 groups. Results There were 7502 diagnosed and 12,974 undiagnosed cases with elevated glycemic status included in the study. During 1999–2016, the intake of low-quality carbohydrates was lower, whereas intakes of high-quality carbohydrates, animal protein, plant protein, and unsaturated fat and the Healthy Eating Index 2015 (HEI-2015) score were higher, among the diagnosed cases than among the undiagnosed cases (P  < 0.001 for all). However, in the trend analyses from 1999 to 2016, the increase in intake of high-quality carbohydrates was smaller among the diagnosed cases than among the undiagnosed cases (difference: −1.16%; 95% CI: −1.82%, −0.50%; P  = 0.001). Moreover, the decrease in low-quality carbohydrate intake was smaller (difference: 0.79%; 95% CI: 0.01%, 1.57%; P  = 0.05) and the increase in saturated fat intake was larger (difference: 0.44%; 95% CI: 0.08%, 0.79%; P  = 0.02) among the diagnosed cases than among the undiagnosed cases. A significant difference of temporal trends in the HEI-2015 score between the diagnosed and undiagnosed cases was also observed, in favor of the undiagnosed cases (difference: −2.56; 95% CI: −3.71, −1.41; P  < 0.001). Conclusions Although dietary habits among adults with diagnosed diabetes and prediabetes were better than those among the undiagnosed cases, these advantages have been diminishing during the past 2 decades. [ABSTRACT FROM AUTHOR]

Background The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. Objectives To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. Methods This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003–2004, 2011–2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. Results The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P -trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P -trend = 0.03). In addition, a linear dose–response relation between serum selenium (range: 89–182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P  < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. Conclusions Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background Several individual studies have shown that circulating levels of odd-chain SFAs and very-long-chain SFAs (VLSFAs) may have beneficial effects, but the results are mixed. While the dietary and metabolic factors that may influence VLSFAs are not well-known, a previous study observed associations of VLSFA concentrations with variants in serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3) gene. Objectives We investigated the associations of individual plasma SFAs and SPTLC3 gene rs680379 polymorphism with metabolic risk factors and type 2 diabetes (T2D). Methods We measured plasma SFAs using gas chromatography among 898 T2D cases and 1618 matched controls, and genotyped the SPTLC3 gene rs680379 polymorphism using the MassArray System among 1178 T2D cases and 1907 matched controls. Conditional logistic regression was used to estimate ORs and 95% CIs. Results We found that plasma odd-chain SFAs and VLSFAs were correlated with favorable blood lipids and insulin resistance marker profiles. After multivariable adjustment, pentadecanoic acid (15:0) was inversely associated with the odds of T2D (OR per 1 SD difference: 0.63; 95% CI: 0.57, 0.70), as were measurements of 3 individual VLSFAs [arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)], with ORs ranging from 0.60 to 0.72 (95% CIs ranging between 0.52 and 0.79). The associations between 3 individual VLSFAs and T2D were attenuated after further adjustment for triglycerides. Meanwhile, compared with the rs680379 GG genotype carriers, the ORs of T2D for the GA and AA genotype carriers were 0.81 (95% CI: 0.68–0.97) and 0.76 (95% CI: 0.61–0.96), respectively. Conclusions Plasma 15:0 and VLSFAs were inversely associated with T2D. Meanwhile, compared with the rs680379 GG genotype carriers, subjects with GA and AA genotypes were associated with decreased odds of T2D. More investigations are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography–tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption. [ABSTRACT FROM AUTHOR]

Background: The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear. Objective: The aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study. Design: A 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24–32 wk of gestation). An independent-phase study,with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who hadGDMscreened during 24–32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted inWuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography–tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test. Results: In the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47). Conclusions: Consistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: The association of trimethylamine- N -oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent. Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms. Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped. Results: Medians (IQRs) of plasma TMAO concentration were 1.47 μmol/L (0.81-2.20 μmol/L) for controls and 1.77 μmol/L (1.09-2.80 μmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) ( P -trend < 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed ( P = 0.093). Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894., (© 2017 American Society for Nutrition.)

Background: Epidemiologic studies have shown inverse associations between nut consumption and diabetes, cardiovascular disease (CVD), and all-cause mortality, but results have not been consistent., Objective: We assessed the relation between nut intake and incidence of type 2 diabetes, CVD, and all-cause mortality., Design: We searched PubMed and EMBASE for all prospective cohort studies published up to March 2013 with RRs and 95% CIs for outcomes of interest. A random-effects model was used to pool risk estimates across studies., Results: In 31 reports from 18 prospective studies, there were 12,655 type 2 diabetes, 8862 CVD, 6623 ischemic heart disease (IHD), 6487 stroke, and 48,818 mortality cases. The RR for each incremental serving per day of nut intake was 0.80 (95% CI: 0.69, 0.94) for type 2 diabetes without adjustment for body mass index; with adjustment, the association was attenuated [RR: 1.03; 95% CI: 0.91, 1.16; NS]. In the multivariable-adjusted model, pooled RRs (95% CIs) for each serving per day of nut consumption were 0.72 (0.64, 0.81) for IHD, 0.71 (0.59, 0.85) for CVD, and 0.83 (0.76, 0.91) for all-cause mortality. Pooled RRs (95% CIs) for the comparison of extreme quantiles of nut intake were 1.00 (0.84, 1.19; NS) for type 2 diabetes, 0.66 (0.55, 0.78) for IHD, 0.70 (0.60, 0.81) for CVD, 0.91 (0.81, 1.02; NS) for stroke, and 0.85 (0.79, 0.91) for all-cause mortality., Conclusions: Our meta-analysis indicates that nut intake is inversely associated with IHD, overall CVD, and all-cause mortality but not significantly associated with diabetes and stroke. The inverse association between the consumption of nuts and diabetes was attenuated after adjustment for body mass index. These findings support recommendations to include nuts as part of a healthy dietary pattern for the prevention of chronic diseases., (© 2014 American Society for Nutrition.)