Publications

AIMS

To investigate whether 25-hydroxyvitamin D concentration was associated with incident diabetes in a large cohort of older women.

METHODS

Data were analysed from women included in the Study of Osteoporotic Fractures, a cohort of community-dwelling women aged ≥65 years at enrolment. Serum 25-hydroxyvitamin D concentration was assessed at the year 6 visit, as were BMI and other factors associated with vitamin D and/or diabetes. Diabetes status was determined at each subsequent visit by self-report and medication use. Only those without prevalent diabetes at the year 6 visit were included in the present analysis (N = 5463, mean age 76.5 years).

RESULTS

During a mean ±sd follow-up of 8.6 ± 4.4 years, incident diabetes was reported in 320 participants. The mean BMI was higher in those with a 25-hydroxyvitamin D concentration <20 ng/ml (<50 nmol/l) than in those with concentrations 20-30 or ≥30 ng/ml [50-74 or ≥75 nmol/l (P < 0.0001)]. A higher 25-hydroxyvitamin D concentration was associated with a 13% lower risk of incident diabetes after adjustment for age and clinic site [hazard ratio 0.87, 95% CI 0.76-0.99, per sd increase in 25-hydroxyvitamin D]; however, the addition of BMI to the model attenuated the estimated effect (hazard ratio 0.97, 95% CI 0.86-1.11). Adjustment for additional potential confounders yielded similar results.

CONCLUSIONS

Serum 25-hydroxyvitamin D does not independently predict incident diabetes in older women. Although those with higher 25-hydroxyvitamin D concentrations are less likely to develop diabetes, this is mainly explained by their lower BMI.

BACKGROUND

The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population.

METHODS

We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression.

RESULTS

In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups.

CONCLUSION

Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.

Tissue fibrosis occurs when matrix production outpaces matrix degradation. Degradation of collagen, the main component of fibrotic tissue, is mediated through an extracellular proteolytic pathway and intracellular pathway of cellular uptake and lysosomal digestion. Recent studies demonstrate that disruption of the intracellular pathways can exacerbate fibrosis. These pathways are poorly characterized. Here we identify novel mediators of the intracellular pathway of collagen turnover through a genome-wide RNA interference screen in Drosophila S2 cells. Screening of 7505 Drosophila genes conserved among metazoans identified 22 genes that were required for efficient internalization of type I collagen. These included proteins involved in vesicle transport, the actin cytoskeleton, and signal transduction. We show further that the flotillin genes have a conserved and central role in collagen uptake in Drosophila and human cells. Short hairpin RNA-mediated silencing of flotillins in human monocyte and fibroblasts impaired collagen uptake by promoting lysosomal degradation of the endocytic collagen receptors uPARAP/Endo180 and mannose receptor. These data provide an initial characterization of intracellular pathways of collagen turnover and identify the flotillin genes as critical regulators of this process. A better understanding of these pathways may lead to novel therapies that reduce fibrosis by increasing collagen turnover.