Dataset Information

Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study.

ABSTRACT: OBJECTIVE:Accumulating evidence has linked elevated parathyroid hormone (PTH) with insulin resistance, beta cell dysfunction and dysglycaemia, however, its role in the development of diabetes is largely unclear, particularly among non-whites. We sought to examine the association of PTH with the incidence of diabetes. METHODS:We studied 8066 white and 2034 black adults aged 46-70 years at baseline (1990-92) from the ARIC Study with follow-up for incident diabetes ascertained during study visits conducted in 1993-95 and 1996-98. Hazard ratios (HR) and their 95% CIs for diabetes adjusted for demographics, lifestyle, and 25-hydroxyvitamin D were estimated according to PTH measured at baseline. RESULTS:PTH was higher among blacks than whites (median [IQR], 43.8 [35.0-55.8] vs. 37.9 [30.4-47.3] pg/mL; P<0.001). During a median follow-up of 6 years, 498 white and 167 black participants developed diabetes. The association of PTH with diabetes varied significantly by race (P-interaction 0.02). PTH was not associated with risk for diabetes among black adults. Among whites, HRs according to quintiles of PTH were 1 (referent), 0.95 (0.71, 1.29), 0.95 (0.70, 1.28), 1.12 (0.84, 1.51), and 1.31 (0.98, 1.76) (P-trend 0.03). When a clinical cut-point for PTH was applied (?65pg/mL; 5.7% of whites), the HR for diabetes among whites was 1.38 (1.01, 1.88). Results were similar when restricted to participants with normal baseline kidney function. CONCLUSION:In this large, population-based study, elevated PTH was independently associated with risk for diabetes among white, but not black adults. Further studies are needed to elucidate the mechanisms that may underlie this differential association of PTH with diabetes across race groups.

SUBMITTER: Reis JP

PROVIDER: S-EPMC4907832 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study.

Reis J P JP Selvin E E Pankow J S JS Michos E D ED Rebholz C M CM Lutsey P L PL

Diabetes & metabolism 20160115 3

<h4>Objective</h4>Accumulating evidence has linked elevated parathyroid hormone (PTH) with insulin resistance, beta cell dysfunction and dysglycaemia, however, its role in the development of diabetes is largely unclear, particularly among non-whites. We sought to examine the association of PTH with the incidence of diabetes.<h4>Methods</h4>We studied 8066 white and 2034 black adults aged 46-70 years at baseline (1990-92) from the ARIC Study with follow-up for incident diabetes ascertained during ...[more]

PMID: 26782010

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Project description:IntroductionHigher concentrations of serum 25-hydroxyvitamin D (25(OH)D) and lower concentrations of parathyroid hormone (PTH) are associated with lower insulin resistance and incident diabetes in non-Hispanic White and Hispanic Americans. Results are mixed in other populations, with no observational studies in a large multiethnic cohort. The association of serum 25(OH)D with diabetes may vary by adiposity level.Research design and methodsAmong 5611 participants in the Multi-Ethnic Study of Atherosclerosis without diabetes at baseline, cross-sectional associations of serum 25(OH)D with homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β were examined using linear regressions. The association of 25(OH)D with incident diabetes over 9 years was examined using Cox proportional hazard regression.ResultsBlack Americans had the highest proportion of individuals with 25(OH)D<20 ng/mL (61%) and White Americans had the least (17%). Serum 25(OH)D was inversely associated with HOMA-IR in fully adjusted models (-0.34% difference in HOMA-IR per ng/mL higher 25(OH)D, p<0.0001). Longitudinally, a 1 ng/mL higher serum 25(OH)D was associated with 2% lower risk of incident diabetes (HR 0.982, CI 0.974 to 0.991), and a 1 pg/mL higher serum PTH was associated with 1% higher risk of incident diabetes (HR 1.007, CI 1.004 to 1.010), both prior to adjustment for waist circumference. After adjusting for waist circumference, a 1 ng/mL higher 25(OH)D was associated with 1% lower risk of incident diabetes (HR 0.991, CI 0.983 to 1.000). The magnitude of association of serum 25(OH)D with incident diabetes was largest at lower waist circumference (p for interaction=0.025). There was no heterogeneity by race/ethnicity (p=0.317).ConclusionsSerum 25(OH)D is inversely associated with insulin resistance and incident diabetes in a diverse cohort, including non-Hispanic White, Black, Hispanic and Chinese Americans. Future research should explore mechanisms for the interaction between serum 25(OH)D and adiposity in this relationship.

Project description:IntroductionAortic stiffness offers important insight into vascular aging and cardiovascular disease (CVD) risk. The referent measure of aortic stiffness is carotid-femoral pulse wave velocity (cfPWV). cfPWV can be estimated (ePWV) from age and mean arterial pressure. Few studies have directly compared the association of ePWV to measured cfPWV, particularly in non-White adults. Moreover, whether ePWV and cfPWV correlate similarly with CVD risk remains unexplored.Aim(1) To estimate the strength of the agreement between ePWV and cfPWV in both Black and White older adults; and (2) to compare the associations of ePWV and cfPWV with CVD risk factors and determine whether these associations were consistent across races.Methods and resultsWe evaluated 4478 [75.2 (SD 5.0) years] Black and White older adults in the Atherosclerosis Risk in Communities (ARIC) Study. cfPWV was measured using an automated pulse waveform analyzer. ePWV was derived from an equation based on age and mean arterial pressure. Association and agreement between the two measurements were determined using Pearson's correlation coefficient (r), standard error of estimate (SEE), and Bland-Altman analysis. Associations between traditional risk factors with ePWV and cfPWV were evaluated using linear mixed regression models. We observed weak correlations between ePWV and cfPWV within White adults (r = 0.36) and Black adults (r = 0.31). The mean bias for Bland-Altman analysis was low at -0.17 m/s (95%CI: -0.25 to -0.09). However, the inspection of the Bland-Altman plots indicated systematic bias (P < 0.001), which was consistent across race strata. The SEE, or typical absolute error, was 2.8 m/s suggesting high variability across measures. In models adjusted for sex, prevalent diabetes, the number of prevalent cardiovascular diseases, and medication count, both cfPWV and ePWV were positively associated with heart rate, triglycerides, and fasting glucose, and negatively associated with body mass index (BMI) and smoking status in White adults (P < 0.05). cfPWV and ePWV were not associated with heart rate, triglycerides, and fasting glucose in Black adults, while both measures were negatively associated with BMI in Black adults.ConclusionsFindings suggest a weak association between ePWV and cfPWV in older White and Black adults from ARIC. There were similar weak associations between CVD risk factors with ePWV and cfPWV in White adults with subtle differences in associations in Black adults.

Project description:DNA methylation studies of incident type 2 diabetes in US populations are limited, and to our knowledge none included individuals of African descent living in the US. We performed an epigenome-wide association analysis of blood-based methylation levels at CpG sites with incident type 2 diabetes using Cox regression in 2,091 Black and 1,029 White individuals from the Atherosclerosis Risk in Communities study. At an epigenome-wide significance threshold of 10-7, we detected 7 novel diabetes-associated CpG sites in C1orf151 (cg05380846: HR= 0.89, p = 8.4 × 10-12), ZNF2 (cg01585592: HR= 0.88, p = 1.6 × 10-9), JPH3 (cg16696007: HR= 0.87, p = 7.8 × 10-9), GPX6 (cg02793507: HR= 0.85, p = 2.7 × 10-8 and cg00647063: HR= 1.20, p = 2.5 × 10-8), chr17q25 (cg16865890: HR= 0.8, p = 6.9 × 10-8), and chr11p15 (cg13738793: HR= 1.11, p = 7.7 × 10-8). The CpG sites at C1orf151, ZNF2, JPH3 and GPX6, were identified in Black adults, chr17q25 was identified in White adults, and chr11p15 was identified upon meta-analyzing the two groups. The CpG sites at JPH3 and GPX6 were likely associated with incident type 2 diabetes independent of BMI. All the CpG sites, except at JPH3, were likely consequences of elevated glucose at baseline. We additionally replicated known type 2 diabetes-associated CpG sites including cg19693031 at TXNIP, cg00574958 at CPT1A, cg16567056 at PLBC2, cg11024682 at SREBF1, cg08857797 at VPS25, and cg06500161 at ABCG1, 3 of which were replicated in Black adults at the epigenome-wide threshold. We observed modest increase in type 2 diabetes variance explained upon addition of the significantly associated CpG sites to a Cox model that included traditional type 2 diabetes risk factors and fasting glucose (increase from 26.2% to 30.5% in Black adults; increase from 36.9% to 39.4% in White adults). We examined if groups of proximal CpG sites were associated with incident type 2 diabetes using a gene-region specific and a gene-region agnostic differentially methylated region (DMR) analysis. Our DMR analyses revealed several clusters of significant CpG sites, including a DMR consisting of a previously discovered CpG site at ADCY7 and promoter regions of TP63 which were differentially methylated across all race groups. This study illustrates improved discovery of CpG sites/regions by leveraging both individual CpG site and DMR analyses in an unexplored population. Our findings include genes linked to diabetes in experimental studies (e.g., GPX6, JPH3, and TP63), and future gene-specific methylation studies could elucidate the link between genes, environment, and methylation in the pathogenesis of type 2 diabetes.

Dataset Information

Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study.

Publications

Parathyroid hormone is associated with incident diabetes in white, but not black adults: The Atherosclerosis Risk in Communities (ARIC) Study.

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