Nuclear Magnetic Resonance-Based Metabolomics and Risk of CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY: The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Differences in HDL-related coronary heart disease risk between individuals with and without diabetes.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes. METHODS: We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD. RESULTS: During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32-1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73-0.86), but higher risks among diabetics (1.38, 1.02-1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics. CONCLUSIONS: Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study.

BACKGROUND: The association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) remains unclear. OBJECTIVE: The aim was to evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD. METHODS: The study included 4651 individuals with fatty liver disease (FLD; 3964 had MAFLD and 3968 had NAFLD) from NHANES III. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the HRs and 95% CIs, with adjustment of potential confounders. RESULTS: Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 y, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HRs and 95% CIs of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001) and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinear inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall < 0.001; Pnonlinear = 0.003) or NAFLD (Poverall < 0.001; Pnonlinear = 0.009), with a threshold effect at ∼50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 y (P-interaction = 0.001). CONCLUSIONS: This study suggested a nonlinear inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at ∼50.0 nmol/L of serum 25(OH)D.

Dietary Intake and Circulating Concentrations of Carotenoids and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Observational Studies.

Previous meta-analysis studies have indicated inverse associations between some carotenoids and risks of metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. However, the results for associations between carotenoids and type 2 diabetes (T2D) remain inconsistent and no systematic assessment has been done on this topic. We conducted a systematic review and meta-analysis to examine the associations of dietary intakes and circulating concentrations of carotenoids with risk of T2D. We searched PubMed and Ovid Embase from database inception to July 2020. Prospective observational studies of carotenoids and T2D risk were included. Random-effects models were used to summarize the RRs and 95% CIs. Thirteen publications were included. Dietary intake of ß-carotene was inversely associated with the risk of T2D, and the pooled RR comparing the highest with the lowest categories was 0.78 (95% CI: 0.70, 0.87; I2 = 13.7%; n = 6); inverse associations were also found for total carotenoids (n = 2), α-carotene (n = 4), and lutein/zeaxanthin (n = 4), with pooled RRs ranging from 0.80 to 0.91, whereas no significant associations were observed for ß-cryptoxanthin and lycopene. Circulating concentration of ß-carotene was associated with a lower risk of T2D, and the pooled RR comparing extreme categories was 0.60 (95% CI: 0.46, 0.78; I2 = 56.2%; n = 7); inverse associations were also found for total carotenoids (n = 3), lycopene (n = 4), and lutein (n = 2), with pooled RRs ranging from 0.63 to 0.85, whereas no significant association was found for circulating concentrations of α-carotene and zeaxanthin when comparing extreme categories. Dose-response analysis indicated that nonlinear relations were observed for circulating concentrations of α-carotene, ß-carotene, lutein, and total carotenoids (all P-nonlinearity < 0.05), but not for other carotenoids or dietary exposures. In conclusion, higher dietary intakes and circulating concentrations of total carotenoids, especially ß-carotene, were associated with a lower risk of T2D. More studies are needed to confirm the causality and explore the role of foods rich in carotenoids in prevention of T2D. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42020196616.

[Association of the polymorphism in manganese superoxide dismutase gene with diabetic retinopathy in Chinese type 2 diabetic patients].

OBJECTIVE: To investigate the association of the polymorphism in manganese superoxide dismutase (Mn-SOD) gene in Chinese type 2 diabetic patients with diabetic retinopathy. METHODS: The Ala(-9)Val polymorphism of the Mn-SOD gene was determined by polymerase chain reaction and direct sequencing in 198 normal control subjects and 264 patients with type 2 diabetes mellitus, among them there were 139 non-diabetic retinopathy (NDR) subjects and 125 subjects with diabetic retinopathy (DR). RESULTS: There was no statistic difference in the frequencies of VV genotype and V allele between the type 2 diabetic group and the control group. However, the frequencies of VV genotype and V allele were significantly higher in the DR group than that in the NDR group (chi-square (2)=5.015, P=0.025; chi(2)=10.253, P=0.001),but there was no statistic difference in the NDR group compared with the control group (P > 0.05). The presence of V allele was shown to be associated with diabetic retinopathy (OR=1.96, 95%CI: 1.29-2.97). Furthermore, the subjects carrying the VV genotype had lower serum Mn-SOD level (P=0.025) and had a tendency of higher total serum SOD activity, but this tendency had no statistic significance. CONCLUSION: The Ala(-9)Val polymorphism in the Mn-SOD gene may not be related to the etiology of type 2 diabetes, but it seems to contribute to the development of diabetic retinopathy in Chinese type 2 diabetic patients.

[Clinical effect of Prunellae Oral Liquid on goiter with different thyroid function].

OBJECTIVE: To observe the clinical effects of Prunellae Oral Liquid (POL) on the size of thyroid with different states of thyroid function in patients of goiter. METHODS: Fifty-six patients with hyperthyroidism, 24 with hypothyroidism and 18 with simple goiter were randomized into two groups. Group A treated by classical therapy, Group B by POL based on classical therapy. Size of thyroid of patients before and after treatment was measured by color ultrasonic Doppler and compared with the data obtained from 20 healthy subjects as control. RESULTS: Size of thyroid in all patients before treatment were obviously larger than that of normal control (P<0.01), but it reduced after treatment in both groups, especially in group B, in which it differed insignificantly to that in the normal control (P > 0.05). CONCLUSION: Combined treatment of Chinese medicine (using POL) and Western medicine is superior to Western medicine alone in treating goiter with different states of thyroid function.

[Clinical effect of prunrllae oral solution in treating hyperthyrea].

OBJECTIVE: To observe the clinical effects of prunrllae oral solution in treating hyperthyrea. METHOD: 56 cases with hyperthyrea were randomized into two groups; group A1 was treated by classic method, B1 was treated by classic method combined with prunrllae oral solution. The size, vessel caliber of thyroidea, volume of blood flow and blood flow rate pre-and post-treatment were measured by color supersonic, meanwhile, 20 normal thyroidea were measured as control group. RESULT: The size and vessel caliber of thyroidea of the two groups pre-treatment were obviously bigger than those of the control group, the volume of blood flow and blood flow rate were obviously slower than those of the control group (P < 0.001), the sizes of thyroidea of the two groups became smaller, especially the group B1 was more obvious, and there was no significant difference in the size of thyroidea between group B1 and control group. CONCLUSION: It is indicated that combined treatment of traditional Chinese medicine (prunrllae oral solution) and western medicine is superior to western medicine in treating hyperthyrea.