Date on Master's Thesis/Doctoral Dissertation

12-2017

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Epidemiology and Population Health

Degree Program

Public Health Sciences with a specialization in Epidemiology, PhD

Committee Chair

Groves, Frank

Committee Co-Chair (if applicable)

Baumgartner, Kathy

Committee Member

Baumgartner, Kathy

Committee Member

Baumgartner, Richard

Committee Member

Rai, Shesh

Committee Member

Winters, Stephen

Abstract

Experimental and epidemiological studies have reported positive associations between iron parameters and metabolic dysfunction including: Type 2 diabetes mellitus (T2DM) (1-6), metabolic syndrome (7-15), non-alcoholic fatty liver disease (NAFLD) (16-22) and insulin resistance (23,24) with a number of studies showing that reductions in total body iron via dietary modification (e.g., reducing red meat intake) or phlebotomy lead to increases in insulin sensitivity (25), decreases in insulin resistance (26), and reductions in the prevalence of complications associated with T2DM (5, 27), metabolic syndrome (28) and NAFLD (22, 29). Moreover, the risk associated with these outcomes and total body iron differ between males and females and it has been hypothesized that the divergence in risk of disease due to total body iron is related to the female reproductive lifespan (e.g., age at menarche, parity, oral contraceptive use and age at menopause). Regardless of study design, serum ferritin and transferrin saturation have consistently been used in these investigations to estimate total iron stores, which are affected by inflammation and demonstrate diurnal variation. The aim of the current study was to examine the clinical utility of an index of iron repletion developed by JD Cook et al. in 1993 (i.e. FeCOOK), which is unaltered by inflammation or liver function in a nationally-representative, community-dwelling, non-institutionalized group of females participating in continuous NHANES from 2003 to 2010 and to examine the association between the index and metabolic dysfunction. The current results highlight the clinical utility of FeCOOK in assessing the iron status in females of reproductive age. I did not observe a statistically significant association between metabolic dysfunction and continuously-scaled FeCOOK. However, when FeCOOK was modeled in accordance with common reporting patterns (i.e., categorically), significant, positive associations between increasing FeCOOK and metabolic dysfunction were observed among all females, and this pattern persisted after stratification by ethnicity and menopausal status. Further research is warranted to examine the clinical utility of FeCOOK among other cohorts. Moreover, additional research using FeCOOK is recommended in order to replicate these findings among a larger sample comprised of both males and older females.

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