Associations of Lower-Carbohydrate and Lower-Fat Diets with Mortality among People with Cardiovascular Disease.

BACKGROUND: Although low-carbohydrate and low-fat diets have been shown to have short-term metabolic benefits, the associations of these dietary patterns, particularly different food sources and macronutrient quality, with mortality in people with cardiovascular disease (CVD) remain unclear. OBJECTIVES: To examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality in individuals with CVD. METHODS: This study included 3971 adults with CVD from the NHANES 1999-2014. Mortality status was linked to National Death Index mortality data through 31 December 2019. 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 hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Higher healthy LCD score was associated with favorable blood lipids and higher homeostasis model assessment of insulin resistance, whereas higher unhealthy LFD score was associated with lower high-density lipoprotein and higher C-reactive protein at baseline (all P-trend < 0.05). During 35,150 person-years of follow-up, 2163 deaths occurred. For per 20-percentile increment in dietary scores, the multivariate-adjusted HRs of all-cause mortality were 0.91 (95% CI: 0.86, 0.96) for healthy LCD score (P < 0.001), 0.94 (95% CI: 0.89, 1.00) for healthy LFD score (P = 0.04), and 1.07 (95% CI: 1.00, 1.14) for unhealthy LFD score (P = 0.04). CONCLUSIONS: Overall LCD and LFD scores are not associated with total mortality. Unhealthy LFD scores are associated with higher total mortality, whereas healthy LCD and LFD scores are associated with lower mortality in people with CVD.

Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.

BACKGROUND: Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear. OBJECTIVES: This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers. METHODS: The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014). Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: After 35,632 person-y of follow-up, 1174 deaths were documented. Higher nut consumption was significantly associated with a lower risk of all-cause mortality among individuals with T2D. After multivariable adjustment including lifestyles and dietary factors, diabetes duration, and glycated hemoglobin, compared with participants who did not consume nuts, the HR (95% CI) for those who consumed nuts over 3.5 ounce equivalent (oz.eq)/wk was 0.64 (0.50, 0.82; P-trend < 0.001) for all-cause mortality. A linear dose-response relationship was observed between nut consumption and all-cause mortality among individuals with T2D (Poverall=0.004, Pnonlinearity=0.35). In substitution analyses, replacing one serving of red and processed meat, refined grains, eggs, and dairy foods with one serving of nuts was associated with a 18% to 22% lower risk of all-cause mortality. In addition, mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.7% and 9.1% of the relationship between nut consumption with all-cause mortality, respectively. CONCLUSIONS: Higher nut consumption was significantly associated with lower all-cause mortality among individuals with T2D. These findings indicate a potential benefit of nut consumption in the prevention of premature death among individuals with T2D.

Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes.

PURPOSE: Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D. METHODS: The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003-2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose-response relationship. RESULTS: After a median follow-up of 17.3 years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9 µmol/L). Furthermore, the dose-response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0 µmol/L (all Poverall < 0.05, Pnonlinearity < 0.05). In contrast, among those with T2D in the similar concentration range, higher serum vitamin C levels (ranged from 0.46 to 116.26 µmol/L) were linearly associated with lower all-cause and cancer mortality (both Poverall < 0.05, Pnonlinearity > 0.05). Significant additive interaction was observed between diabetes status and serum vitamin C levels with regard to all-cause and cancer mortality (P < 0.001). In addition, C-reactive protein, gamma-glutamyl transpeptidase, and HbA1c explained 14.08, 8.96, and 5.60% of the association between serum vitamin C and all-cause mortality among individuals with T2D, respectively. CONCLUSIONS: Higher serum vitamin C concentrations were significantly associated with lower risk of mortality in participants with T2D in a linear dose-response manner, while a nonlinear association was observed in participants without T2D, with an apparent threshold around 48.0 µmol/L. These findings suggest that the optimal vitamin C requirement may differ in individuals with and without T2D.

Effects of healthy low-carbohydrate diet and time-restricted eating on weight and gut microbiome in adults with overweight or obesity: Feeding RCT.

The effect of a healthy low-carbohydrate diet (HLCD) and time-restricted eating (TRE), alone or in combination, on body weight and gut microbiome beyond caloric restriction remains unclear. In this 12-week two-by-two factorial randomized trial with a 28-week follow-up among 96 participants with overweight or obesity, isocaloric-restricted feeding yields significant weight loss, ranging from 2.57 to 4.11 kg across different groups. Beyond caloric restriction, HLCD and TRE lead to additional reduction in body mass index. HLCD results in additional fat mass loss while TRE yields more lean mass loss. Additionally, HLCD leads to decreased fecal branched-chain amino acids, and TRE tends to yield an increased abundance of probiotic species involved in synthesizing short-chain fatty acids. Moreover, the effect of HLCD on reducing fat mass is sustained during the post-intervention follow-up. Overall, HLCD and TRE are effective in weight management and yield profound gut microbiome and metabolome alteration beyond caloric restriction. This study was registered at ChiCTR.org.cn (ChiCTR2200056363).

Vitamin D and heart failure risk among individuals with type 2 diabetes: observational and Mendelian randomization studies.

BACKGROUND: Evidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common. OBJECTIVES: This study aimed to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks. METHODS: Observational analyses were performed among 15,226 T2D participants aged 40-72 y from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants. RESULTS: The mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 y, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0-74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99). CONCLUSIONS: Higher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D.

Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications among Individuals with Type 2 Diabetes.

OBJECTIVE: To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among people with type 2 diabetes, and to further explore the potential mediating role of metabolism-related biomarkers. RESEARCH DESIGN AND METHODS: This study included 20,338 participants with type 2 diabetes from UK Biobank. Diabetic complications were identified through hospital inpatient records. RESULTS: During 13.2 years of follow-up, 5,396 people developed macrovascular complications, and 4,868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease; and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD; and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammation collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD. CONCLUSIONS: Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.

Association of healthy sleep pattern with risk of recurrent cardiovascular events among patients with coronary heart disease.

AIMS: To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD). METHODS AND RESULTS: This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness. Cox proportional hazards regression models were applied to estimate the associations between healthy sleep score and recurrent cardiovascular events. During a median of 11.1 years of follow up, we documented 3771 recurrent cardiovascular events, including 1634 heart failure cases and 704 stroke cases. After multivariable adjustment, including lifestyle factors, medical history, and CHD duration, sleep 7-8 h/day, never/rarely insomnia, and no frequent daytime sleepiness were each significantly associated with a 12-22% lower risk of heart failure. In addition, compared with participants who had a healthy sleep score of 0-1, the multivariable-adjusted HR (95% CI) for participants with a healthy sleep score of 4 was 0.86 (0.75, 0.99) for recurrent cardiovascular events, 0.71 (0.57, 0.89) for heart failure, and 0.72 (0.51, 1.03) for stroke. CONCLUSIONS: Adherence to a healthy sleep pattern was significantly associated with a lower risk of recurrent cardiovascular events among patients with CHD, especially for heart failure. These findings indicate that healthy sleep behaviours could be beneficial in the prevention of cardiovascular event recurrence.

Combined exposure to multiple air pollutants and incident ischemic heart disease in individuals with and without type 2 diabetes: A cohort study from the UK Biobank.

BACKGROUND: Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. METHODS: This study included 388780 individuals (20036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters between 2.5 and 10 µm (PMcoarse), PM with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen dioxides (NOx), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. RESULTS: During a median of 12.9 years of follow-up, 27333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03-1.23) among individuals with T2D, while the HR was 1.06 (1.03-1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (Pinteraction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. CONCLUSIONS: The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

CONTEXT: Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. OBJECTIVE: We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. METHODS: This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate ß values and 95% CI. RESULTS: After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (ß -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. CONCLUSION: These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

Associations of Serum 25(OH)D With Risk of Recurrent Cardiovascular Events in Individuals With Coronary Heart Disease.

CONTEXT: Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD). OBJECTIVE: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD. METHODS: A total of 22 571 participants with CHD were included from the UK Biobank. Recurrent CV events, including myocardial infarction (MI), heart failure (HF), stroke, and CV disease mortality, were identified from electronic health records. Cox proportional-hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: The median (interquartile range) of serum 25(OH)D concentration was 44.8 nmol/L (range, 30.3-61.4 nmol/L), and 58.6% of participants had 25(OH)D below 50 nmol/L. During a median follow-up of 11.2 years, a total of 3998 recurrent CV events were documented. After multivariable adjustment, there was a nonlinear inverse relationship between serum 25(OH)D and recurrent CV events (P nonlinearity <.01), and the decreasing risk gradually leveled off at around 50 nmol/L. Compared with participants with serum 25(OH)D less than 25.0 nmol/L, the HRs (95% CIs) for participants with serum 25(OH)D of 50.0 to 74.9 nmol/L were 0.64 (0.58-0.71) for recurrent CV events, 0.78 (0.65-0.94) for MI, 0.66 (0.57-0.76) for HF, and 0.66 (0.52-0.84) for stroke. In addition, these associations were not modified by genetic variants in the VDR. CONCLUSION: In people with established CHD, higher serum 25(OH)D concentrations were nonlinearly associated with a lower risk of recurrent CV events, with a potential threshold around 50 nmol/L. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of recurrent CV events among individuals with CHD.

Complete Genome Insights into Lactococcus petauri CF11 Isolated from a Healthy Human Gut Using Second- and Third-Generation Sequencing.

Lactococcus petauri CF11 was originally isolated from the gut of healthy humans. To determine the underlying molecular and genetic mechanisms of the probiotic potential of CF11, we performed complete genome sequencing, annotation, and comparative genome analysis. The complete genome of L. petauri CF11 comprised of 1,997,720 bp, with a DNA G+C content of 38.21 mol% containing 1982 protein coding genes and 16 rRNA operons. We found that 1206 genes (56.05%) were assigned a putative function using the gene ontology (GO) resource. The gene products of CF11 were primarily concentrated in molecular function and biological processes, such as catalysis, binding, metabolism, and cellular processes. Furthermore, 1,365 (68.87%) genes were assigned an illative function using COGs. CF11 proteins were associated with carbohydrate transport and metabolism, and amino acid transport and metabolism. This indicates that CF11 bacteria can perform active energy exchange. We classified 1,111 (56.05%) genes into six KEGG functional categories; fructose-bisphosphate aldolase and the phosphoenol pyruvate:phosphotransferase system (PTS), which are necessary in producing short-chain fatty acids (SCFAs), were excited in the carbohydrate metabolic pathway. This suggests that L. petauri CF11 produces SCFAs via glycolysis. The genomic island revealed that some regions contain fragments of antibiotic resistance and bacteriostatic genes. In addition, ANI analysis showed that L. petauri CF11 had the closest relationship with L. petauri 159469T, with an average nucleotide consistency of 98.03%. Taken together, the present study offers further insights into the functional and potential role of L. petauri CF11 in health care.