Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults.
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ABSTRACT:
SUBMITTER: Zhang Y
PROVIDER: S-EPMC7585682 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults.
Zhang Yuanyuan Y Zhou Chun C Li Jianping J Zhang Yan Y Xie Di D Liang Min M Wang Binyan B Song Yun Y Wang Xiaobin X Huo Yong Y Hou Fan Fan FF Xu Xiping X Qin Xianhui X
Cardiovascular diabetology 20201024 1
<h4>Background</h4>The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.<h4>Methods</h4>A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary out ...[more]
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Project description:The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.
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Project description:BackgroundSerum sodium level is associated with cardiovascular and endocrine health. Though decreased serum sodium is considered to be associated with reduced hypertension risk, some studies also found that it may increase the risk of diabetes. This study aimed to investigate the association of serum sodium with new-onset diabetes in hypertensive patients.MethodsBased on the annual health examinations from 2011 to 2016 in Dongguan City, Guangdong, China, hypertensive patients without diabetes at baseline were selected. Logistic regression and restricted cubic spline were used to evaluate the association between serum sodium level and new-onset diabetes. Subgroup analysis was also conducted.ResultsA total of 4438 hypertensive patients with a mean age of 58.65 years were included, of whom 48.9% were male. During a median follow-up of 35.1 months, 617 (13.9%) of the subjects developed new-onset diabetes. Per 1-SD (3.39 mmol/L) increment of serum sodium was associated with a 14% lower risk of new-onset diabetes (odds ratio = 0.86; 95% CI: 0.78, 0.97; p = 0.01). The lowest quartile of serum sodium was associated with the lowest diabetes risk. The restricted cubic spline showed a linear inverse relationship (nonlinear p = 0.72). Across all the subgroups, the inverse association was consistent (p for interaction >0.05).ConclusionAn inverse association of serum sodium with new-onset diabetes in hypertensive patients was observed.
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Project description:This study aimed to provide insights into the relationship between lipid levels and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without diabetes (6056 men and 8808 women) aged 45-75 years from the China Stroke Primary Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined as fasting plasma glucose (FPG)???7.0?mmol/L at the end of study or self-reported physician diagnosis of diabetes or self-reported use of hypoglycemic agents during follow-up) was analyzed using multivariate analysis. Follow-up was censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD (10.9%, men?=?10.8% and women?=?10.9%). Increased triglycerides (TG) [odds ratio (OR)?=?1.18; 95% confidence interval (CI): 1.13-1.25, P?<?0.001], TG/HDL (OR?=?1.12; 95%CI: 1.08-1.17, P?<?0.001), and decreased high density lipoprotein (HDL) (OR?=?0.79; 95%CI: 0.67-0.93, P?=?0.005) were associated with NOD, independently from age, gender, body mass index, clinical center, systolic blood pressure, diastolic blood pressure, FPG, smoking, and drinking. Compared to subjects with the methylenetetrahydrofolate reductase (MTHFR) 677 CC and TT genotypes, those with the CT genotype had a higher risk of NOD (OR?=?1.54; 95%CI: 1.30-1.81, P for interaction?=?0.044) in subjects with high TG. These results suggested that TG and TG/HDL were independent risk factors for NOD in this Chinese hypertensive population. HDL was a protective factor for NOD.
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Project description:BACKGROUND: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. RESULTS: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10?²¹, 1.12 × 10??? and 2.82 × 10?²? for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. CONCLUSIONS: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations.
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Project description:In the present genome-wide association study of 2,994 Japanese subjects, rs2071699 (35C>T) in the fucosyltransferase 1 (FUT1) gene was identified as a marker associated with serum alkaline phosphatase (ALP) levels. This gene encodes ?(1,2)-fucosyltransferase, which is responsible for the synthesis of H antigens. In a linear regression model incorporating genetic markers, rs550057 (C>T), which is located within an intron of the ABO blood group (ABO) locus, rs2071699 in FUT1 and a gene-gene interaction between these loci accounted for 12.4, 0.9 and 0.3% of the total variability in the serum ALP level, respectively. Further association analysis using imputed genotypes detected rs1047781 in FUT2. rs1047781 is well known in this association with serum ALP levels and showed a moderate linkage with rs2071699 in FUT1. An interaction analysis using rs1047781 in FUT2 also suggested that the interaction with rs550057 in ABO is significant and contributes to the interindividual variance of serum ALP levels as well as rs2071699 in the FUT1 gene. Thus, there is evidence of interactions between ABO and FUT1/FUT2 on serum ALP levels, regardless of the possibility that rs2071699 in FUT1 is a proxy of rs1047781 in FUT2 in the Japanese population.
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Project description:This retrospective study included 299 patients with type 2 diabetes mellitus and biopsy-confirmed diabetic nephropathy (DN) to investigate the prognostic value of alkaline phosphatase (ALP) for renal outcome. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for the serum ALP level on renal outcome, which was defined as end-stage renal disease (ESRD) or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. The median baseline ALP was 80 IU/L with an interquartile range of 64-97 IU/L. Serum ALP was negatively associated with eGFR but positively associated with proteinuria and renal interstitial fibrosis. During a median follow-up period of 23 months, ESRD or a 50% declined in the eGFR occurred in 156 (52.2%) patients. The highest quartile of ALP was significantly associated with poor renal outcome, as defined above (HR 2.38, 95% confidence interval [CI] 1.09-5.17), when adjusted for sociodemographics, baseline eGFR, proteinuria, liver function parameters, parathyroid hormone levels, and renal pathological findings. Each standard deviation higher in the natural log-transformed ALP was associated with a 25% increased risk for poor renal outcome. Additionally, there was a graded increase in the risk for poor renal outcome with higher ALP in patients with nephrotic-range proteinuria. However, no significant associations were observed between serum ALP levels and renal outcome in patients with non-nephrotic-range proteinuria. In conclusion, an elevated ALP level was independently associated with poor renal outcome in patients with type 2 diabetes mellitus and nephrotic-range proteinuria after multivariate adjustment.
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Project description:Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008-2011) was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR): >120, 90-119, 60-89, and <60 mL/min/1.73 m2. The participants with eGFR >120 mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876-7.892), compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329). ALP quartiles were significantly associated with albuminuria in participants with eGFR ? 60 ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005). After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002). In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.
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