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: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.

Project description:Carotid intima-media thickness has been reported to predict kidney function decline. However, whether carotid intima-media thickness is associated with a hard kidney end point, ESRD, has not been investigated.We studied 13,197 Atherosclerosis Risk in Communities participants at visit 1 (1987-1989) without history of cardiovascular disease, including coronary heart disease, stroke, and heart failure, at baseline and assessed whether carotid intima-media thickness measured by B-mode ultrasound is associated with ESRD risk using Cox proportional hazards models. Regarding carotid intima-media thickness parameters, we investigated the mean and maximum values of overall and segment-specific (common, bifurcation, and internal carotid arteries) measurements.Mean age was 54.0 (SD=5.7) years old, and there were 3373 (25.6%) blacks and 7370 (55.8%) women. During a median follow-up of 22.7 years, 433 participants developed ESRD (1.4/1000 person-years). After adjusting for shared risk factors for atherosclerosis and kidney disease, including baseline kidney function, carotid intima-media thickness was significantly associated with ESRD risk (hazard ratio [HR] between quartiles 4 and 1, 1.46; 95% confidence interval [95% CI], 1.02 to 2.08 for overall mean intima-media thickness and HR between quartiles 4 and 1, 1.75; 95% CI, 1.24 to 2.48 for overall maximum intima-media thickness). The associations were largely consistent in demographic and clinical subgroups. When we explored segment-specific intima-media thicknesses, the associations with ESRD were most robust for bifurcation carotid (e.g., adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.49; 95% CI, 1.04 to 2.13 for bifurcation; adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.36; 95% CI, 0.94 to 1.97 for common; and adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 0.93; 95% CI, 0.67 to 1.29 for internal).Carotid intima-media thickness was independently associated with incident ESRD in the general population, suggesting the shared etiology of atherosclerosis and ESRD.

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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