Background Although dietary supplements are commonly taken to avoid chronic disease, long-term health consequences of many compounds are unknown. Methods We assessed the use of vitamin and mineral supplements in relation to total mortality in 38 772 older women in the Iowa Women's Health Study, mean age 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997 and 2004. Through December 31, 2008, 15 594 deaths (40.2%) were identified through the State Health Registry of Iowa and the National Death Index. Results In multivariable adjusted proportional hazards regression models, the use of multivitamins (Hazard Ratio (HR), 1.06 [95% CI, 1.02-1.10], Absolute Risk Increase (ARI), 2.4%), vitamin B6 (HR, 1.10 [95% CI, 1.01-1.21], ARI, 4.1%), folic acid (HR, 1.15 [95% CI, 1.00-1.32], ARI, 5.9%), iron (HR, 1.10 [95% CI, 1.03-1.17], ARI, 3.9%), magnesium (HR, 1.08 [95% CI, 1.01-1.15], ARI, 3.6%), zinc (HR, 1.08 [95% CI, 1.01-1.15], ARI, 3.0%) and copper (HR, 1.45 [95% CI, 1.20-1.75], ARI, 18.0%) were associated with increased risk of total mortality when compared with corresponding nonusers, while calcium was inversely related (HR, 0.91 [95% CI, 0.88-0.94], Absolute Risk Reduction (ARR), 3.8%). Findings for iron and calcium were replicated in separate shorter-term analyses (10-year, 6-year and 4-year follow-up) each with about 15% dead, starting in 1986, 1997, and 2004. Conclusion In older women several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk, most strongly supplemental iron, while calcium, in contrast to many studies, was associated with decreased risk.

OBJECTIVEAlthough cumulative evidence suggests that increased oxidative stress may lead to insulin resistance in vivo or in vitro, community-based studies are scarce. This study examined the longitudinal relationships of oxidative stress biomarkers with the development of insulin resistance and whether these relationships were independent of obesity in nondiabetic young adults.RESEARCH DESIGN AND METHODSBiomarkers of oxidative stress (F2-isoprostanes [F2Isop] and oxidized LDL [oxLDL]), insulin resistance (the homeostasis model assessment of insulin resistance [HOMA-IR]), and various fatness measures (BMI, waist circumference, and estimated percent fat) were obtained in a population-based observational study (Coronary Artery Risk Development in Young Adults) and its ancillary study (Young Adult Longitudinal Trends in Antioxidants) during 2000–2006.RESULTSThere were substantial increases in estimated mean HOMA-IR over time. OxLDL and F2Isop showed little association with each other. Mean evolving HOMA-IR increased with increasing levels of oxidative stress markers (P < 0.001 for oxLDL and P = 0.06 for F2Isop), measured in 2000–2001. After additional adjustment for adiposity, a positive association between oxLDL and HOMA-IR was strongly evident, whereas the association between F2Isop and HOMA-IR was not.CONCLUSIONSWe observed positive associations between each of two oxidative stress markers and insulin resistance. The association with oxidized LDL was independent of obesity, but that with F2Isop was not.

OBJECTIVECompelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM.RESEARCH DESIGN AND METHODSWe performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982–1983 and 1986–1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards.RESULTSDuring 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73–1.14), 0.78 (0.62–0.99), 0.72 (0.57–0.91), and 0.76 (0.60–0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear.CONCLUSIONSAt dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk.

The prevalence of IDA in early childhood is significantly larger in low-income infants and toddlers living in VLFS households. Asian, Hispanic and African-American children have elevated prevalences of ID and IDA. Breast-feeding may be associated with elevated ID and IDA, while participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) may be protective for ID.

We evaluated the effect of the pregnane X receptor (PXR) agonist rifampin on metformin pharmacokinetics, organic cation transporter 1 (OCT1) and OCT2 mRNA levels, and glucose levels, using the oral glucose tolerance test (OGTT) in 16 healthy subjects. The glucose-lowering effects of metformin were evaluated by OGTT before and after metformin treatment on days 1 and 2 and again on days 13 and 14 after a 10-day course of rifampin. Rifampin increased the difference in maximum glucose levels (ΔG(max)) by 41.9% (P = 0.024) and the area under the concentration-time curve (AUC) during the first 60 min after glucose ingestion (ΔAUC(gluc60)) by 54.5% (P = 0.020). Renal clearance (CL(R)) of metformin was increased by 16% (P = 0.008), but the systemic exposure was only slightly increased (13%, P = 0.049), possibly because of increased absorption. Rifampin increased OCT1 mRNA levels 4.1-fold in peripheral blood cells (P = 0.001); however, OCT2 mRNA was not detected. Our results suggest that rifampin increases OCT1 expression and hepatic uptake of metformin, leading to enhanced glucose-lowering action.

No abstract

Aims/hypothesis We examined the cross-sectional and longitudinal relationships between C-reactive protein (CRP), a marker of low-grade inflammation, and insulin resistance and whether the association was independent of obesity and oxidative stress. Methods CRP and insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) data were obtained in a population-based, prospective observational study, Coronary Artery Risk Development in Young Adults (CARDIA), during 1992–2006. Results CRP showed a significant positive association with insulin resistance, both cross-sectionally and longitudinally (5 year follow-up). The estimated increment in HOMA-IR was 0.34 loge(pmol/l×[mmol/l]/156.25) (p value for trend <0.0001) in the highest vs lowest CRP quartiles in cross-sectional analysis, whereas the corresponding estimate was 0.12 (p trend <0.0001) in the highest vs lowest CRP quartiles longitudinally over 5 years. The gradient of HOMA-IR across CRP was attenuated but remained statistically significant after controlling for body fat measurements (0.06 in the highest vs lowest CRP in both cross-sectional [p value for trend=0.001] and longitudinal analyses [p value for trend=0.01]), and was little changed by further adjustment for oxidative stress markers (F2-isoprostanes and oxidised LDL). There were consistent increments in the levels of HOMA-IR with increasing concentrations of CRP over time. In contrast, higher HOMA-IR did not predict future increases in CRP. Findings were similar using fibrinogen as the predictor variable. Conclusions/interpretation Although a substantial portion of this association was explained by obesity, CRP was independently related to concurrent and future insulin resistance.

We quantitatively assessed the association between a vegetarian diet and diabetes risk using pooled estimates from observational studies. Electronic database searches for articles published from January 1980 to May 2016 were independently performed by two investigators, and 13 articles (14 studies) were identified. The pooled odds ratio (OR) for diabetes in vegetarians vs. non-vegetarians was 0.726 (95% confidence interval (CI): 0.608, 0.867). In the subgroup analyses, this inverse association was stronger for the studies conducted in the Western Pacific region (OR 0.514, 95% CI: 0.304, 0.871) and Europe/North America (OR 0.756, 95% CI: 0.589, 0.971) than studies conducted in Southeast Asia (OR 0.888, 95% CI: 0.718, 1.099). No study had a substantial effect on the pooled effect size in the influence analysis, and the Egger’s (p = 0.465) and Begg’s tests (p = 0.584) revealed no publication bias. This meta-analysis indicates that a vegetarian diet is inversely associated with diabetes risk. Our results support the need for further investigations into the effects of the motivations for vegetarianism, the duration of the adherence to a vegetarian diet, and type of vegetarian on diabetes risk.