RESUMO
BACKGROUND: Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes. OBJECTIVE: By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes. DESIGN: A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes. RESULTS: Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47% lower risk of diabetes (95% CI: 23%, 63%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33% (95% CI: 6%, 53%; P-trend: 0.02) and 37% (95% CI: 11%, 55%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32% lower risk for fourth vs. first quartile; P-trend: 0.04). CONCLUSIONS: These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at clinicaltrials.gov as NCT00005133.
Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Ácidos Graxos não Esterificados/sangue , Fosfolipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus/prevenção & controle , Dieta , Ácidos Eicosanoicos/sangue , Ácidos Graxos/sangue , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Observacionais como Assunto , Ácido Palmítico/sangue , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangueRESUMO
Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.
Assuntos
Arsênio/urina , Arsenicais/urina , Poluentes Ambientais/urina , Glutationa Transferase/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Estudos de Casos e Controles , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Polimorfismo Genético , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/urinaRESUMO
OBJECTIVE: We sought to assess whether the metabolism of arsenic impacts a person's susceptibility to bladder cancer. METHODS: Urinary methylation products were measured in subjects from Argentina (114 cases and 114 controls) and the United States (23 cases and 49 controls). RESULTS: In Argentina, the adjusted odds ratio (OR) for subjects with a high proportion of ingested arsenic excreted as monomethylarsonate (%MMA) was 2.17 (95% confidence interval [CI] = 1.02-4.63) in smokers and 0.48 (95% CI = 0.17-1.33) in nonsmokers. In the United States, the adjusted ORs for high %MMA in subjects with arsenic intakes less than and greater than 100 microg/d were 1.20 (95% CI = 0.27-5.38) and 2.70 (95% CI = 0.39-18.6). CONCLUSIONS: Overall, these results are consistent with data from Taiwan suggesting that some individuals who excrete a higher proportion of ingested arsenic as MMA are more susceptible to arsenic-related cancer.
Assuntos
Arsênio/metabolismo , Neoplasias da Bexiga Urinária/induzido quimicamente , Idoso , Argentina , Arsênio/urina , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Razão de Chances , Estados Unidos , Neoplasias da Bexiga Urinária/etiologiaRESUMO
Studies have found increased bladder cancer risks associated with high levels of arsenic in drinking water, but little information exists about risks at lower concentrations. Ecologic studies in Argentina have found increased bladder cancer mortality in Córdoba Province, where some wells are contaminated with moderate arsenic concentrations. This population-based bladder cancer case-control study in two Córdoba counties recruited 114 case-control pairs, matched on age, sex, and county, during 1996-2000. Water samples, particularly from wells, were obtained from subjects' current residences and residences in the last 40 years. Statistical analyses showed no evidence of associations with exposure estimates based on arsenic concentrations in drinking water. However, when well-water consumption per se was used as the exposure measure, time-window analyses suggested that use of well water more than 50 years before interview was associated with increased bladder cancer risk. This association was limited to ever smokers (odds ratio = 2.5, 95% confidence interval: 1.1, 5.5 for 51-70 years before interview), and the possibility that this association is due to chance cannot be excluded. This study suggests lower bladder cancer risks for arsenic than predicted from other studies but adds to evidence that the latency for arsenic-induced bladder cancers may be longer than previously thought.