The development of Type 2 diabetes mellitus (Type 2 DM) in California twins.

摘要

Chapter One 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 Two 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%) (p0.0001); 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 Three 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. (Abstract shortened by UMI.)