Date of Award

1-1-2018

Embargo Period

3-14-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Public Health Sciences

College

College of Graduate Studies

First Advisor

Marvella E. Ford

Second Advisor

Anbesaw Selassie

Third Advisor

Sharon D. Yeatts

Fourth Advisor

Renee' Hebert Martin

Fifth Advisor

Gayenell Magwood

Sixth Advisor

Keith Borg

Abstract

Since 1980, the prevalence of obesity and diabetes mellitus (or diabetes) in the US has each increased over 200%. Furthermore, obesity and diabetes are each a risk factor for the incidence of an ischemic stroke and are each independently associated with clinical outcomes following an ischemic stroke (e.g., functional disability, all-cause mortality, and cardiovascular-related mortality). To date, no study has investigated the presence of a joint effect of obesity and diabetes on clinical outcomes following an ischemic stroke. Further, no study has illustrated the extent to which misclassification and measurement error are present in exposure assessment of obesity within a cohort of ischemic stroke survivors. Based on recent research that has supported the heterogeneity of the metabolic profile among obese individuals coupled with prior scientific evidence of the presence of a joint effect, or interaction effect, of obesity and diabetes on the risk of stroke, it is hypothesized that the effect of obesity on clinical outcomes following an ischemic stroke may differ according to diabetes status. The overarching goals of this dissertation were to determine if a joint effect of obesity and diabetes on clinical outcomes following an ischemic stroke exists and to illustrate issues related to measures of obesity. The dissertation addressed five specific aims. A post-hoc analysis using data from the Interventional Management of Stroke (IMS) III clinical trial and the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) clinical trial were used in this dissertation. The IMS III clinical trial informed Specific Aims 1-2. Additionally, data from the PRoFESS clinical trial were used to examine Specific Aims 3-4. Specific Aim 5 illustrates the extent to which misclassification and measurement error were present in exposure assessment of obesity using data from the PRoFESS clinical trial. In the post-hoc analysis of the IMS III data, there was not sufficient evidence to declare that the effect of obesity on functional disability as well as on all-cause mortality differed by diabetes status on the multiplicative or additive scales. Using data from the PRoFESS trial, there was insufficient evidence to conclude that the effect of obesity on all-cause mortality differed by diabetes status on either the multiplicative or additive scale. In contrast, there was evidence that the effect of obesity on cardiovascular-related mortality differed by diabetes status on the multiplicative scale and the attributable proportion due to interaction of the additive scale. However, there was insufficient evidence of an additive interaction for the relative excess risk due to interaction for this outcome. Furthermore, this dissertation also sought to illustrate the extent to which misclassification and measurement error were present in exposure assessment of obesity based on the anthropometric measures of body mass index (BMI), waist circumference, and waist circumference-to-height ratio within a cohort of ischemic stroke survivors using data from the PRoFESS clinical trial. Of the three anthropometric measures, BMI was the best at discriminating the patient-relevant clinical outcome of all-cause mortality following an ischemic stroke. However, all of the anthropometric measures were barely able to discriminate between subjects with and without the outcome slightly better than chance (area under the curve ≤ 0.60). Error in measurement may impact outcomes of obesity and, therefore, will not reflect the true magnitude of the problem. Overall, this dissertation was the first to investigate the joint effect of obesity and diabetes on clinical outcomes following an ischemic stroke. The results of this dissertation support recent research of the heterogeneity of the metabolic profile among obese individuals. This work also highlights the need for future research to improve calibration of the available measures of obesity and/or to develop alternative methods for determining body adiposity.

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