Insulin resistance (IR) is well documented in type 1 diabetes (T1D) and is theorized to relate to diabetes complications, including renal and coronary artery disease (CAD). The hyperinsulinemic-euglycemic clamp technique provides accurate assessment of IR, yet the laborious, costly, and invasive nature of this technique is often inappropriate for large investigations. Increasing use of the Estimated Glucose Disposal (eGDR) equation in T1D makes further examination of this equation desirable as it may be improved with additional assessments. Leg adiposity has been favorably associated with IR and cardiovascular risk, but whether this protective tendency is similar in T1D populations is unknown. This dissertation examines whether diabetes complications or additional clinical factors (i.e. regional adiposity distribution) contributes to the estimation of IR in T1D. Differences in regional adiposity, and the extent to which these differences influence IR, were examined in T1D and individuals without diabetes. Associations between CAD risk factors and regional adiposity were also investigated in individuals with T1D.
No differences in IR were observed between T1D individuals with CAD or renal disease. All adiposity measures were detrimentally associated with IR, however, general obesity most strongly predicted IR in this population. Despite lower levels of adiposity, more severe IR was observed in individuals with T1D compared to non-diabetic individuals. Leg adiposity was favorably associated with presence of CAD, even after controlling for general obesity, but this association was only observed in non-diabetes and in T1D individuals who were obese. Trunk and leg fat displayed equal yet opposite associations with CAD risk factors and increasing leg adiposity was associated with decreased risk for the presence of CAD in females with T1D.
This dissertation thus yields significant Public Health findings by providing evidence that IR is a prominent feature in T1D, is largely driven by adiposity, and can be estimated using clinical measures. Furthermore, the finding that leg adiposity was favorably associated with presence of CAD in individuals with T1D provides impetus to further study and underscores the complex association of adiposity with morbidity in T1D.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06092009-135735 |
| Date | 28 September 2009 |
| Creators | Shay, Christina Marie |
| Contributors | Elsa M. Strotmeyer, Ph.D., M.P.H., Trevor J. Orchard, M.D., M.Med.Sci., Bret H. Goodpaster, Ph.D., Sheryl F. Kelsey, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06092009-135735/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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