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THE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS (TYPE 2 DM) IN
CALIFORNIA TWINS
by
Pei-Jung Tsai
May 2011
Copyright 2011 Pei-Jung Tsai
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements of the Degree
DOCTOR OF PHILOSOPHY
(EPIDEMIOLOGY)
Object Description
| Title | The development of type 2 diabetes mellitus (type 2 DM) in California twins |
| Author | Tsai, Pei-Jung |
| Author email | katherinetsai@yahoo.com; pjt1101@yahoo.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Epidemiology |
| School | Keck School of Medicine |
| Date defended/completed | 2011-03-22 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-05-04 |
| Advisor (committee chair) | Mack, Thomas M. |
| Advisor (committee member) |
Cozen, Wendy Hamilton, Ann S. Watanabe, Richard M. Buchanan, Thomas A. |
| Abstract | Previous studies have shown that the development of type 2 diabetes mellitus (Type 2 DM) is affected by multiple genetic and environmental factors. Numerous family and twin studies have provided evidence showing that the risk of Type 2 DM is elevated among families and twins if another family member or co-twin has the disease [Serjeantson et al. 1983]. The familial aggregation [Cauchi et al. 2008, Watanabe et al. 2007, Yi et al. 2005, Prunier et al. 2004, Prestwich et al. 2007, Cossu et al. 1999, McLin et al. 2007] and higher concordance rate found in monozygotic (MZ) twins compares to dizygotic (DZ) twins [Fehmann et al. 1995, Florez et al. 2006, Lyssenko et al. 2007, Shu et al. 2008, Cauchi et al. 2008, Chimieti et al. 2005, Sladek et al. 2007, Steinthorsdottir et al. 2007, Chimienti et al. 2006, Taylor et al. 2005, Simon et al. 2001, Raz et al. 1989] points to the possibility of genetic influence in the development of Type 2 DM. However, familial aggregation and twin concordance support not only a genetic factor in the development of Type 2 DM but also the possibility of shared environmental influences. Despite the attempts by various types of studies including family studies [Cauchi et al. 2008, Watanabe et al. 2007, Yi et al. 2005, Prunier et al. 2004, Prestwich et al. 2007, Cossu et al. 1999, McLin et al. 2007], twin studies [Fehmann et al. 1995, Florez et al. 2006, Lyssenko et al. 2007, Shu et al. 2008, Cauchi et al. 2008, Chimieti et al. 2005, Sladek et al. 2007, Steinthorsdottir et al. 2007, Chimienti et al. 2006, Taylor et al. 2005, Simon et al. 2001, Raz et al. 1989), observational studies (Martin et al. 1992, Assd et al. 1991, Ling et al. 2004, Carlsson et al. 2005, Winckler et al. 2007, Deeb et al. 1998, Altshuler et al. 2000, Yasuda et al. 2008, Unoki et al. 2008, Sandhu et al. 2007], genetic linkage studies [Pearson et al. 2007, Lyssenko et al. 2005, Ahlzen et al. 2008, Weedon et al. 2006, Wasserfall et al. 2006, Ahmann et al. 2006,; Blonde et al. 2007, Gottlieb et al. 1968, Tattersall et al. 1972, Barnett et al. 1981, Newman et al. 1987], and association studies [Poulsen et al. 1999, poulsen et al. 2009, Condon et al. 2008, Serjeantson et al. 1984, Stancakova et al. 2009, Gloyn et al. 2008, Schmidt et al. 2008], the mechanisms involving genetic factors and environmental influences on the development of Type 2 DM are still unclear. Chapter 1 provides the introduction to the background of the literature review and the 2 papers conducted to examine the dissertation hypotheses.; Chapter 2 provides a literature review of the genetic susceptibility in type 2 diabetes including identified and known candidate genes and genetic variants found in different geographic populations in the past decades or so.; Chapter 3 provides the details of the study designs, statistical analysis, study results, and discussion in a draft paper tilted “Genetic Susceptibility to Type 2 Diabetes May Be Modified by Shared Early Environment”. Briefly, the background, methods, results, and conclusion is as following:; Background: Genetic and environmental factors have been implicated in development of type 2 diabetes. We assessed these factors using a population-based twin registry.; Methods: A follow-up study of 92 monozygotic (MZ) and 198 dizygotic (DZ) pairs with self-reported type 2 diabetes in at least one member was conducted. The twins were first ascertained in 1992 from the California Twin Program (CTP), and the follow-up dates were from January, 1997 to December, 2001. The concordance rates and disease discordant probability of initially unaffected co-twins were examined using the proband method and Kaplan-Meier method, respectively.; Results: Genetic susceptibility to type 2 diabetes was suggested by higher concordance rates in MZ compared to DZ twins at baseline and after follow-up (53% vs. 36%, and 77% vs. 53%); lower disease discordant probability after 15 years in MZ (22%) vs. DZ twins (58%) (p<0.0001); a shorter time interval between the first and second diagnosis in MZ (5.79+4.32 years) compared to DZ concordant pairs (7.39+4.17 years) (p= 0.037); and a higher proportion of parents with diabetes among concordant pairs than discordant pairs. However, among MZ twins, disease discordant probability was longer among those who shared the same room for 16 years or longer compared to those who moved apart sooner (28.8% vs. 7.6%) (p=0.0177).; Conclusions: Our findings support prior estimates of type 2 diabetes concordance in MZ twins but suggest that concordance in DZ twins may have been underestimated. Furthermore, disease discordant probability may be modified by shared early environmental factors which remain to be determined.; Chapter 4 provides the details of the study designs, statistical analysis, study results, and discussion in a draft paper tilted “The Smoking and Height at Teens and Type 2 Diabetes Risk in California Twins”. Briefly, the background, methods, results, and conclusion is as following:; Background: Type 2 diabetes is thought to be a heterogeneous and complex disease presumably with a multi-factorial etiology consisting of genetic and environmental factors and often manifest later in adult life. This current study is aimed to assess the association of environmental factors and type 2 diabetes adjusting for genetic susceptibility by using population-based twin registry.; Methods: This was a matched case-control study nested in the California Twin Program (CTP) and conditional multivariate logistic regressions were used to determine odds ratios for childhood/adolescent and adult lifestyle factors in 161 discordant twin pairs (126 dizygotic (DZ) and 35 monozygotic (MZ) pairs).; Results: The faster growth rate and taller in height at teens was associated with an increased risk of developing type 2 diabetes in MZ (Matched Odds Ratio (OR)=20.04, 95% confidence interval (CI): 2.01-72.28) and DZ (Matched OR=8.74, 95%CI: 4.48-17.04) discordant twin pairs. In addition, adolescent smoking was also associated with an increased risk for type 2 diabetes in DZ discordant twins (Matched OR=1.72, 95%CI: 1.04-2.85).; Conclusions: Irrespective of the age of type 2 diabetes onset in adulthood (i.e. after age 35), childhood/adolescent as well as adult lifestyle factors were associated with Type 2 diabetes; therefore indicating the potential importance of early prevention efforts.; Chapter 5 provides the details of the summary, conclusions, and future plans. |
| Keyword | type 2 diabetes; type 2 diabetes mellitus; genetic susceptibility; monozygotic; MZ; dizygotic; DZ; disease discordant probability; genetic susceptibility; body mass index; smoking; monozygotic; MZ; dizygotic; DZ; adjusted odds ratio; adjusted OR |
| Geographic subject (state) | California |
| Geographic subject (country) | USA |
| Coverage date | 1972/2008 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3885 |
| Rights | Tsai, Pei-Jung |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Tsai-4423 |
| Archival file | uscthesesreloadpub_Volume29/etd-Tsai-4423.pdf |
Description
| Title | Page 1 |
| Full text | THE DEVELOPMENT OF TYPE 2 DIABETES MELLITUS (TYPE 2 DM) IN CALIFORNIA TWINS by Pei-Jung Tsai May 2011 Copyright 2011 Pei-Jung Tsai A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements of the Degree DOCTOR OF PHILOSOPHY (EPIDEMIOLOGY) |
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