Dataset Information

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.

ABSTRACT:

Objective

Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study.

Research design and methods

A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ? 126 mg/dL, 2-h glucose ? 200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications.

Results

Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations.

Conclusions

Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.

SUBMITTER: Kuo CC

PROVIDER: S-EPMC4370323 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.

Kuo Chin-Chi CC Howard Barbara V BV Umans Jason G JG Gribble Matthew O MO Best Lyle G LG Francesconi Kevin A KA Goessler Walter W Lee Elisa E Guallar Eliseo E Navas-Acien Ana A

Diabetes care 20150112 4

<h4>Objective</h4>Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study.<h4>Research design and methods</h4>A total of 1,694 diabetes-free participants aged 45-75 years were recruited in 1989-1991 and followed through 1998-1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DM ...[more]

PMID: 25583752

Similar Datasets

Project description:BackgroundHigh arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity.ObjectiveWe evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.MethodsWe included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up.ResultsMedian ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants.ConclusionsAmong participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

Project description:BackgroundInorganic arsenic exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes; however, this profile has also been associated with increased risk for diabetes-related outcomes. The mechanism behind these contrasting associations is equivocal; we hypothesized one carbon metabolism (OCM) may play a role.MethodsWe evaluated the association between OCM-related variables (nutrient intake and genetic variants) and both arsenic metabolism biomarkers (iAs%, MMA% and DMA%) and diabetes-related outcomes (metabolic syndrome, diabetes, HOMA2-IR and waist circumference) in 935 participants free of prevalent diabetes and metabolic syndrome from the Strong Heart Family Study, a family-based prospective cohort comprised of American Indian tribal members aged 14+ years.ResultsOf the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 years of follow-up and of the 1458 participants free of diabetes at baseline, 167 (11.3%) developed diabetes over follow-up. OCM nutrients were not associated with arsenic metabolism, however, higher vitamin B6 was associated with diabetes-related outcomes (higher HOMA2-IR and increased risk for diabetes and metabolic syndrome). A polymorphism in an OCM-related gene, methionine synthase (MTR), was associated with both higher MMA% (β = 2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR = 0.79, 95% CI = 0.66, 0.93 per 5 years of follow-up). Adjustment for OCM variables did not affect previously reported associations between arsenic metabolism and diabetes-related outcomes; however, the association between the MTR variant and diabetes-related outcomes were attenuated after adjustment for arsenic metabolism.ConclusionsOur findings suggest MMA% may be a partial mediator in the association between OCM and diabetes-related outcomes. Additional mediation analyses with longer follow-up period are needed to confirm this finding. Further research is needed to determine whether excess B vitamin intake is associated with increased risk for diabetes-related outcomes.

Project description:ObjectiveThe objective of this study was to evaluate the association between measures of body composition and patterns of urine arsenic metabolites in the 1989-1991 baseline visit of the Strong Heart Study, a cardiovascular disease cohort of adults recruited from rural communities in Arizona, Oklahoma, North Dakota and South Dakota.MethodsWe evaluated 3,663 Strong Heart Study participants with urine arsenic species above the limit of detection and no missing data on body mass index, % body fat and fat free mass measured by bioelectrical impedance, waist circumference and other variables. We summarized urine arsenic species patterns as the relative contribution of inorganic (iAs), methylarsonate (MMA) and dimethylarsinate (DMA) species to their sum. We modeled the associations of % arsenic species biomarkers with body mass index, % body fat, fat free mass, and waist circumference categories in unadjusted regression models and in models including all measures of body composition. We also considered adjustment for arsenic exposure and demographics.ResultsIncreasing body mass index was associated with higher mean % DMA and lower mean % MMA before and after adjustment for sociodemographic variables, arsenic exposure, and for other measures of body composition. In unadjusted linear regression models, % DMA was 2.4 (2.1, 2.6) % higher per increase in body mass index category (< 25, ?25 & <30, ?30 & <35, ?35 kg/m2), and % MMA was 1.6 (1.4, 1.7) % lower. Similar patterns were observed for % body fat, fat free mass, and waist circumference measures in unadjusted models and in models adjusted for potential confounders, but the associations were largely attenuated or disappeared when adjusted for body mass index.ConclusionMeasures of body size, especially body mass index, are associated with arsenic metabolism biomarkers. The association may be related to adiposity, fat free mass or body size. Future epidemiologic studies of arsenic should consider body mass index as a potential modifier for arsenic-related health effects.

Project description:BackgroundRecent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity.MethodsWe selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU).ResultsAfter 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model.ConclusionsIn this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status. Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.

Dataset Information

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.

Objective

Research design and methods

Results

Conclusions

Publications

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets