Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies.

BACKGROUND: Hypertension, a complex condition, is primarily defined based on blood pressure readings without involving its pathophysiological mechanisms. We aimed to identify biomarkers through a proteomic approach, thereby enhancing the future definition of hypertension with insights into its molecular mechanisms. METHODS: The discovery analysis included 1560 participants, aged 55 to 74 years at baseline, from the KORA (Cooperative Health Research in the Region of Augsburg) S4/F4/FF4 cohort study, with 3332 observations over a median of 13.4 years of follow-up. Generalized estimating equations were used to estimate the associations of 233 plasma proteins with hypertension and systolic blood pressure (SBP). For validation, proteins significantly associated with hypertension or SBP in the discovery analysis were validated in the KORA Age1/Age2 cohort study (1024 participants, 1810 observations). A 2-sample Mendelian randomization analysis was conducted to infer causalities of validated proteins with SBP. RESULTS: Discovery analysis identified 49 proteins associated with hypertension and 99 associated with SBP. Validation in the KORA Age1/Age2 study replicated 7 proteins associated with hypertension and 23 associated with SBP. Three proteins, NT-proBNP (N-terminal pro-B-type natriuretic peptide), KIM1 (kidney injury molecule 1), and OPG (osteoprotegerin), consistently showed positive associations with both outcomes. Five proteins demonstrated potential causal associations with SBP in Mendelian randomization analysis, including NT-proBNP and OPG. CONCLUSIONS: We identified and validated 7 hypertension-associated and 23 SBP-associated proteins across 2 cohort studies. KIM1, NT-proBNP, and OPG demonstrated robust associations, and OPG was identified for the first time as associated with blood pressure. For NT-proBNP (protective) and OPG, causal associations with SBP were suggested.

Proteomic profiling of longitudinal changes in kidney function among middle-aged and older men and women: the KORA S4/F4/FF4 study.

BACKGROUND: Due to the asymptomatic nature of the early stages, chronic kidney disease (CKD) is usually diagnosed at late stages and lacks targeted therapy, highlighting the need for new biomarkers to better understand its pathophysiology and to be used for early diagnosis and therapeutic targets. Given the close relationship between CKD and cardiovascular disease (CVD), we investigated the associations of 233 CVD- and inflammation-related plasma proteins with kidney function decline and aimed to assess whether the observed associations are causal. METHODS: We included 1140 participants, aged 55-74 years at baseline, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort study, with a median follow-up time of 13.4 years and 2 follow-up visits. We measured 233 plasma proteins using a proximity extension assay at baseline. In the discovery analysis, linear regression models were used to estimate the associations of 233 proteins with the annual rate of change in creatinine-based estimated glomerular filtration rate (eGFRcr). We further investigated the association of eGFRcr-associated proteins with the annual rate of change in cystatin C-based eGFR (eGFRcys) and eGFRcr-based incident CKD. Two-sample Mendelian randomization was used to infer causality. RESULTS: In the fully adjusted model, 66 out of 233 proteins were inversely associated with the annual rate of change in eGFRcr, indicating that higher baseline protein levels were associated with faster eGFRcr decline. Among these 66 proteins, 21 proteins were associated with both the annual rate of change in eGFRcys and incident CKD. Mendelian randomization analyses on these 21 proteins suggest a potential causal association of higher tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) level with eGFR decline. CONCLUSIONS: We reported 21 proteins associated with kidney function decline and incident CKD and provided preliminary evidence suggesting a potential causal association between TNFRSF11A and kidney function decline. Further Mendelian randomization studies are needed to establish a conclusive causal association.

The atherogenic index of plasma (AIP) is a predictor for the severity of coronary artery disease.

Objective: Dyslipidemia is a key risk factor for coronary artery disease (CAD). This study aimed to investigate the correlation between the atherogenic index of plasma (AIP) and the severity of CAD. Methods: 2,491 patients were enrolled in this study and analyzed retrospectively, including 665 non-CAD patients as the control group and 1,826 CAD patients. The CAD patients were classified into three subgroups according to tertiles of SYNTAX score (SS). Non-high-density lipoprotein cholesterol (Non-HDL-C) was defined as serum total cholesterol (TC) minus serum high-density lipoprotein cholesterol (Non-HDL-C), atherogenic index (AI) was defined as the ratio of non-HDL-C to HDL-C; AIP was defined as the logarithm of the ratio of the concentration of triglyceride (TG) to HDL-C; lipoprotein combine index (LCI) was defined as the ratio of TC∗TG∗ low-density lipoprotein cholesterol (LDL)to HDL-C; Castelli Risk Index I (CRI I) was defined as the ratio of TC to HDL-C; Castelli Risk Index II (CRI II) was defined as the ratio of LDL-C to HDL-C. Results: The levels of AIP (P < 0.001), AI (P < 0.001), and LCI (P = 0.013) were higher in the CAD group compared with the non-CAD group. The Spearman correlation analysis showed that AIP (r = 0.075, P < 0.001), AI (r = 0.132, P < 0.001), and LCI (r = 0.072, P = 0.001) were positively correlated with SS. The multivariate logistic regression model showed CRI I (OR: 1.11, 95% CI: 1.03-1.19, P = 0.005), CRI II (OR: 1.26, 95% CI: 1.15-1.39, P < 0.001), AI (OR: 1.28, 95% CI: 1.17-1.40, P < 0.001), AIP (OR: 2.06, 95% CI: 1.38-3.07, P < 0.001), and LCI (OR: 1.01, 95% CI: 1.01-1.02, P < 0.001) were independent predictors of severity of CAD After adjusting various confounders. Conclusion: CRI I, CRI II, AIP, AI, and LCI were independent predictors of the severity of CAD, which could be used as a biomarker for the evaluation of the severity of CAD.

Novel biomarkers of inflammation, kidney function and chronic kidney disease in the general population.

BACKGROUND: Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence. METHODS: We used data from two independent population-based studies, KORA F4 (discovery, n = 1110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1672, mean age 61.9 years, 43.6% male). Serum levels of biomarkers were measured using proximity extension assay technology. The association of biomarkers with estimated glomerular filtration rate (eGFR) at baseline and with incident CKD was investigated using linear and logistic regression models adjusted for cardiorenal risk factors. Independent results from prospective analyses of both studies were pooled. The significance level was corrected for multiple testing by false-discovery rate (PFDR < 0.05). RESULTS: In the KORA F4 discovery study, 52 of 71 inflammatory biomarkers were inversely associated with eGFR based on serum creatinine. Top biomarkers included CD40, TNFRSF9 and IL10RB. Forty-two of these 52 biomarkers were replicated in the ESTHER study. Nine of the 42 biomarkers were associated with incident CKD independent of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up 6.5 years) and ESTHER (n = 103, mean follow-up 8 years) studies. Pathway analysis revealed the involvement of inflammatory and immunomodulatory processes reflecting cross-communication of innate and adaptive immune cells. CONCLUSIONS: Novel and known biomarkers of inflammation were reproducibly associated with kidney function. Future studies should investigate their clinical utility and underlying molecular mechanisms in independent cohorts.

Longitudinal association of built environment pattern with DXA-derived body fat in elderly Hong Kong Chinese: a latent profile analysis.

BACKGROUND: One major limitation of prior studies regarding the associations between built environment (BE) and obesity has been the use of anthropometric indices (e.g., body mass index [BMI]) for assessing obesity status, and there has been limited evidence of associations between BE and body fat. This study aimed to explore the longitudinal association between BE and body fat in a cohort of elderly Hong Kong Chinese and examine whether the BE-body fat associations differed by BMI categories. METHODS: Between 2001 and 2003, 3944 participants aged 65-98 years were recruited and followed for a mean of 6.4 years. BE characteristics were assessed via Geographic Information System. Body fat (%) at whole body and regional areas (trunk, limbs, android, and gynoid) were assessed by dual energy X-ray absorptiometry at baseline and three follow-ups. Latent profile analysis was used to derive BE class, and linear mixed-effects models were used to investigate the associations of BE class with changes in body fat. Stratified analyses by BMI categories were also conducted. RESULTS: Three BE classes were identified. Participants in Class 2 (characterized by greater open space and proportion of residential land use) had a slower increase in whole body fat (B = -0.403, 95% confidence interval [CI]: -0.780, -0.014) and limbs fat (-0.471, 95% CI: -0.870, -0.071) compared with participants in Class 1 (characterized by high proportion of commercial land use). There were significant interactions of BE class with BMI, and participants in Class 2 had a slower increase in whole body fat and regional fat compared with participants in Class 1 (B ranging from -0.987 [limbs] to -0.523 [gynoid]) among overweight and obese participants only. CONCLUSIONS: We found that those who resided in the areas characterized by greater open space and proportion of residential land use had a slower body fat increase.

Association of green space with bone mineral density change and incident fracture in elderly Hong Kong Chinese: Mr. OS and Ms. OS study.

BACKGROUND: A large body of literature has reported positive effects of green space (GS) on various aspects of health and well-being, while no studies explore the role of GS in bone health. OBJECTIVES: The present study aimed to investigate the associations of GS with bone mineral density (BMD) change and incident fracture in a prospective cohort of elderly Hong Kong Chinese. METHODS: Between 2001 and 2003, 3944 participants aged 65 years and older at baseline were recruited. GS (%) within 300-m and 500-m buffers were calculated for each participant based on the Normalized Difference Vegetation Index. BMD at whole body, lumbar spine, total hip, and femoral neck were assessed by dual energy X-ray absorptiometry at baseline and 3 follow-ups. Incident fracture cases were ascertained from the electronic database of Hospital Authority of Hong Kong. Linear mixed-effects models and Cox proportional hazards models were used to investigate the associations of GS with changes in BMD and incident fracture, respectively. RESULTS: Greater GS within 300-m and 500-m buffers were associated with a slower increase in lumbar spine BMD over 14 years. After adjustment for potential confounders, ß and 95% confidence intervals (CIs) of change in BMD across Q2-Q4 (quartiles of GS measured in a 300-m, compared with Q1) were -6.42 (-12.3, -0.59), -7.78 (-13.6, -1.97), and -7.83 (-13.7, -2.00) mg/cm3, respectively. GS was also positively associated with non-spinal fracture and major osteoporotic fracture incidence risks. Multivariable-adjusted hazard ratios (95%CIs) were 1.40 (1.09, 1.79; P-trend = 0.036) for non-spinal fracture and 1.53 (1.13, 2.07; P-trend = 0.010) for major osteoporotic fracture (Q4 compared with Q1 of GS measured in a 300-m buffer). Positive GS-fracture associations were also found for GS within a 500-m buffer. CONCLUSIONS: We found that those who lived near higher GS levels had a slower increase in lumbar spine BMD and had higher incident fracture risk.

Socioeconomic status as an effect modifier of the association between built environment and mortality in elderly Hong Kong Chinese: A latent profile analysis.

BACKGROUND: Previous studies have focused on associations between individual built environment (BE) characteristics and mortality, and found the BE-mortality associations differed by socioeconomic status (SES). Different individual BE characteristics may have different impacts on health and thus could interact. Combinations of BE characteristics may be a better approach to explore the BE-mortality associations. OBJECTIVES: This study aimed to investigate the associations of BE pattern with mortality in a prospective cohort of elderly Hong Kong Chinese (Mr. OS and Ms. OS Study), and assess whether the BE-mortality association differed by SES. METHODS: Between 2001 and 2003, 3944 participants aged 65-98 years at baseline were included in the present analysis. BE characteristics were assessed via Geographic Information System. Data on all-cause and cause-specific mortality were obtained from the Hong Kong Government Death Registry. Latent profile analysis was used to derive BE class, and the Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Three BE classes were identified. During a total of 53276 person-years of follow-up, 1632 deaths were observed. There were no significant associations of BE class with all-cause and cause-specific mortality. However, we found the associations of BE class with all-cause mortality were modified by SES. In comparison with Class 3 (characterized by greater green space), HRs (95%CIs) were 0.72 (0.54, 0.97) for Class 1 (characterized by greater commercial land use) and 0.77 (0.64, 0.94) for Class 2 (characterized by greater residential land use) among low-SES participants. The associations were stronger among high-SES participants, with 0.55 (0.33, 0.89) for Class 1 and 0.68 (0.48, 0.97) for Class 2. In contrast, Class 2 (HR 1.18, 95%CI 1.01-1.39) had a higher mortality risk compared with Class 3 among middle-SES participants. CONCLUSIONS: Our findings provide new evidence on the role of SES as an effect modifier of BE pattern and mortality. BE pattern has a varied effect on mortality risk for different SES groups.

Interpretable Machine Learning Framework Reveals Robust Gut Microbiome Features Associated With Type 2 Diabetes.

OBJECTIVE: To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features. RESEARCH DESIGN AND METHODS: We used an interpretable machine learning framework to identify the type 2 diabetes-related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS-type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832). RESULTS: The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23-1.33), 1.23 (1.13-1.34), and 1.12 (1.06-1.18) across three cohorts. The MRS was positively associated with future glucose increment (P < 0.05) and was correlated with a variety of gut microbiota-derived blood metabolites. Animal study further confirmed the MRS-type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome-type 2 diabetes relationship. CONCLUSIONS: Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

Associations between serum total, free and bioavailable testosterone and non-alcoholic fatty liver disease in community-dwelling middle-aged and elderly women.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is considered both a cause and consequence of the metabolic syndrome (MetS). While emerging evidence has indicated that testosterone is associated with MetS, the relationship between testosterone and NAFLD in women remains unclear. Therefore, this study investigated the associations between serum testosterone levels and NAFLD prevalence risk in a community-based cross-sectional study. METHODS: A total of 2117 adult women were included in the analysis. Serum total testosterone (TT) was measured by chemiluminescence immunoassay, and other testosterone-related indices, such as concentrations and percentages of calculated free testosterone (cFT) and bioavailable testosterone (BioT), and free androgen index (FAI), were also calculated. NAFLD was diagnosed by clinical criteria. Logistic regression was used to explore these associations. RESULTS: There were significant differences in TT, FAI, cFT and BioT between women with and without NAFLD (all P<0.001). Multivariate logistic-regression analyses demonstrated that both absolute concentrations and percentages of cFT and BioT were positively associated with NAFLD risk prevalence in all models. Adjusted ORs (95% CI) for quartile 4 vs quartile 1 of % cFT and % BioT were 5.94 (4.29-8.22) and 5.21 (3.79-7.17) in model 2, and 4.35 (3.07-6.18) and 3.58 (2.55-5.03) in model 3 (all P<0.001 for trend). In addition, quartiles of TT, FAI, cFT and BioT were significantly correlated with degree of hepatic steatosis. ROC analysis also showed that % cFT and % BioT were more accurate for predicting NAFLD prevalence than was TT. CONCLUSION: Serum cFT and BioT were positively associated with NAFLD risk, and elevated levels of cFT and BioT could be independent risk factors of NAFLD prevalence in middle-aged and elderly women.

Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study.

OBJECTIVE: To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. RESEARCH DESIGN AND METHODS: We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota. RESULTS: Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota ß-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P < 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes. CONCLUSIONS: Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.

Longitudinal Association of Built Environment Pattern with Physical Activity in a Community-Based Cohort of Elderly Hong Kong Chinese: A Latent Profile Analysis.

A large number of studies have focused on the associations between single built environment (BE) characteristics and physical activity (PA). Combinations of BE characteristics offer a more comprehensive approach to identify the BE-PA associations. We aimed to examine the BE-PA associations in a cohort of elderly Hong Kong Chinese. Between 2001 and 2003, 3944 participants (65-98 years of age) were recruited and followed for a mean of 7.8 years. BE characteristics were assessed via geographic information system. PA levels were obtained using the Physical Activity Scale for the Elderly questionnaire at baseline and three follow-ups. Latent profile analysis was first conducted to classify the BE characteristics, and linear mixed-effects models were then used to explore the longitudinal associations between the BE classes and changes in the PA levels. Three classes of BE were identified. Class 3 (characterized by greater green space and sky view factor) demonstrated a significant decline in household PA (ß = -1.26, 95% confidence interval: -2.20, -0.33) during the study period, and a slower decline in walking PA (1.19 (0.42, 1.95)) compared with Class 2 (characterized by a greater proportion of residential land use). Our results indicate that BE patterns characterized by high green space and a sky view factor may help promote the walking PA level.

Erythrocyte Membrane Polyunsaturated Fatty Acids Are Associated with Incidence of Metabolic Syndrome in Middle-Aged and Elderly People-An 8.8-Year Prospective Study.

BACKGROUND: The total and specific types of polyunsaturated fatty acids (PUFAs) related to metabolic syndrome (MetS) remain inconsistent. OBJECTIVE: We assessed the association of erythrocyte n-3 and n-6 PUFAs with MetS and the components of MetS in a cohort population. METHODS: This prospective analysis included 2754 participants (aged 40-75 y) from the Guangzhou Nutrition and Health Study (2008-2019) in China. Erythrocyte PUFAs at baseline were measured using gas chromatography. MetS was assessed every 3 y according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariable Cox proportional hazard models were used to evaluate HRs and 95% CIs. RESULTS: We identified 716 incident cases of MetS. The primary analyses showed that the HRs (95% CIs) of MetS (tertile 3 versus 1) were 0.67 (0.56, 0.80) for n-3 PUFAs and 0.70 (0.58, 0.85) for n-6 PUFAs (all Ps trend <0.001). The secondary outcomes showed that, higher erythrocyte very-long-chain (VLC) PUFAs [20:3n-3, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), and 22:4n-6], but lower α-linolenic acid (ALA) and γ-linolenic acid (GLA), tended to be associated with lower incidences of MetS and its components; among individual MetS components, the associations of PUFAs were more pronounced for hypertriglyceridemia (HTG) and hypertension, followed by low high-density lipoproten (HDL) cholesterol. Significantly higher concentrations of n-3 PUFAs (total, DPA, and DHA) and n-6 PUFAs (total, ARA, and 22:4) were observed in participants with improved (versus progressed) status of MetS (all Ps trend ≤0.003). CONCLUSION: This study reveals that higher erythrocyte VLC n-3 and n-6 PUFAs, but lower 18-carbon PUFAs (ALA and GLA), are associated with lower risks of MetS components (HTG, hypertension, and low HDL cholesterol) and thereby lower MetS incidence in Chinese adults.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and elderly adults.

OBJECTIVE: Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI. DESIGN: We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography. SETTING: Guangzhou, China. PARTICIPANTS: Guangzhou Nutrition and Health Study participants, aged 40-75 years at baseline (n 3051). RESULTS: After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2-5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD. CONCLUSIONS: Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.

Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study.

CONTEXT: SHBG, a homodimeric glycoprotein produced by hepatocytes has been shown to be associated with metabolic disorders. Whether circulating SHBG levels are predictive of later risk of nonalcoholic fatty liver disease (NAFLD) remains unknown. In this study, we prospectively investigated the association between SHBG and NAFLD progression through a community-based cohort comprising 3389 Chinese adults. METHODS: NAFLD was diagnosed using abdominal ultrasonography. Serum SHBG levels were measured by chemiluminescent enzyme immunometric assay, and their relationship with NAFLD development and regression was investigated after a mean follow-up of 3.09 years using multivariable logistic regression. RESULTS: Basal SHBG was negatively associated with NAFLD development, with a fully adjusted odds ratio (OR) and its 95% confidence interval (CI) of 0.22 (0.12-0.40) (P < .001). In contrast, basal SHBG was positively associated with NAFLD regression, with a fully adjusted OR of 4.83 (2.38-9.81) (P < .001). Multiple-stepwise logistic regression analysis showed that SHBG concentration was an independent predictor of NAFLD development (OR, 0.28 [0.18-0.45]; P < .001) and regression (OR, 3.89 [2.43-6.22]; P < .001). In addition, the area under the receiver operating characteristic curves were 0.764 (95% CI, 0.740-0.787) and 0.762 (95% CI, 0.738-0.785) for the prediction models of NAFLD development and regression, respectively. CONCLUSIONS: Serum SHBG concentration is associated with the development and regression of NAFLD; moreover, it can be a potential biomarker for predicting NAFLD progression, and also a novel preventive and therapeutic target for NAFLD.

Circulating Saturated Fatty Acids and Incident Type 2 Diabetes: A Systematic Review and Meta-Analysis.

The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I2 > 50%) or a fixed effects model (if I2 ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76-0.98; C17:0: 0.76, 0.59-0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09-1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D.

Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study.

PURPOSE: Previous studies have suggested that serum carotenoids might be inversely associated with non-alcoholic fatty liver disease (NAFLD), but little data came from longitudinal studies. We prospectively examined the associations between serum-carotenoid levels and NAFLD severity and the intermediary effects of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR), body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese adults. METHODS: This prospective study included 3336 Chinese adults (40-75 years). We assessed serum concentrations of carotenoids at baseline and determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal ultrasonography was conducted to assess the presence and degree of NAFLD at years 3 and 6. RESULTS: The 2687 subjects who completed both NAFLD tests were classified into stable, improved and progressed groups according to changes in the degree of NAFLD between two visits. Analyses of covariance showed that ln-transformed serum concentrations of α-carotene, ß-cryptoxanthin, ß-carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively associated with NAFLD improvement (all p-trend < 0.05). After multivariable adjustment, mean differences in serum carotenoids were higher by 29.6% (ß-carotene), 18.2% (α-carotene), 15.6% (ß-cryptoxanthin), 11.5% (lycopene), 8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs. progressed subjects. Path analyses indicated the carotenoid-NAFLD association was mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were positively associated with the prevalence and progression of NAFLD. CONCLUSIONS: In middle-aged and elderly adults, higher serum-carotenoid concentrations were favorably associated with NAFLD improvement, mediated by reducing serum RBP4, triglycerides, HOMA-IR, and BMI. TRIAL REGISTRATIONS: This study has been registered at http://www.clinicaltrials.gov as NCT03179657.

Association between erythrocyte fatty acids in de novo lipogenesis pathway and DXA-derived body fat and trunk fat distribution in Chinese adults: a prospective study.

PURPOSE: Higher levels of fatty acids (FAs) in the de novo lipogenesis (DNL) pathway might be associated with higher levels of fat mass (FM), while limited evidence is available from the general population. We aimed to examine the associations between DNL-FAs and body fat and fat distribution in a general population of Chinese adults. METHODS: This community-based prospective cohort study included 3,075 participants (68% women) aged 40-75 years in urban Guangzhou, China. We measured erythrocyte DNL-FAs composition (including C16:0, C16:1n-7, C18:0, and C18:1n-9) at baseline and %FM over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions after 3.2 years and 6.3 years of follow-up, respectively. RESULTS: Generally, higher proportions of individual erythrocyte DNL-FAs and their combined index were positively associated with adipose indices in the multivariable cross-sectional and longitudinal analyses. The cross-sectional percentage mean differences in quartile 4 (vs. 1) of the DNL index were 3.43% (TB), 4.56% (trunk), and 2.67% (A/G ratio) (all P trends < 0.01). The corresponding values in longitudinal changes of adipose indices were 1.40% (TB), 1.78% (trunk), and 1.32% (A) (all P trends < 0.05). The above associations tended to be more pronounced in the trunk and android area than the limbs and gynoid area. CONCLUSIONS: Erythrocyte DNL-FAs may contribute to an increase in total body fat in Chinese adults, particularly FM distributed in trunk and abdominal regions.

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.

BACKGROUND & AIMS: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. METHODS: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. RESULTS: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). CONCLUSIONS: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.

Erythrocyte Saturated Fatty Acids and Incident Type 2 Diabetes in Chinese Men and Women: A Prospective Cohort Study.

The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76; p = 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99; p = 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19; p = 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12; p = 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22; p = 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56; p = 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs.

Higher dietary carotenoid intake associated with lower risk of hip fracture in middle-aged and elderly Chinese: A matched case-control study.

BACKGROUND: Mechanism studies have suggested that carotenoids may benefit bone health due to their antioxidant properties, but epidemiological data on their effects on risk of hip fracture are sparse. PURPOSE: To explore the relationships between dietary total and specific carotenoids and the risk of hip fracture in a middle-aged and elderly Chinese population. DESIGN: A case-control study of 1070 patients with hip fractures (diagnosed within 2 weeks) aged 55-80 years and 1070 age- (within 3 years) and gender-matched controls was conducted in Guangdong, China between 2009 and 2015. Information on dietary carotenoid intake was assessed using a 79-item food frequency questionnaire administered in face-to-face interviews, and general information was collected using structured questionnaires. The univariate and multivariate conditional logistic regression models were applied to analyze the associations. MAIN RESULTS: Higher intakes of both total and some specific carotenoids (including ß-carotene, ß-cryptoxanthin and lutein/zeaxanthin) were significantly associated with a lower risk of hip fracture (all p trends <0.01). Compared with the lowest quartile of carotenoids, the multivariate-adjusted odds ratios and 95% confidential intervals of the highest quartile were 0.44 (0.29, 0.68) (total carotenoids), 0.50 (0.29, 0.69) (ß-carotene), 0.55 (0.38, 0.80) (ß-cryptoxanthin) and 0.40 (0.27, 0.59) (lutein/zeaxanthin), respectively. There were no statistically significant associations between α-carotene and lycopene intakes and hip fracture risk after adjustment for various confounding variables. CONCLUSION: These results suggest that the consumption of carotenoids may be protective against hip fracture in middle-aged and elderly Chinese adults.