The determinants of the excess risk of type-2 diabetes amongst Indian Asians compared to Europeans
File(s)
Author(s)
Sehmi, Jobanpreet Singh
Type
Thesis
Abstract
Background
Indian Asians are at increased risk of type-2 diabetes (T2D), insulin resistance and related
metabolic disturbances compared to Europeans. The contribution of known lifestyle and genetic risk
factors to the excess risk of T2D in Indian
Asians is not well understood.
Methods and materials
I investigated 16,774 Indian Asian and 7,301 European men and women participating in the in the London Life Sciences Population Study to determine the prevalence of T2D and related glycaemic disorders. I examined the contribution of adiposity, leisure time physical activity, major dietary macronutrients and known genetic susceptibility factors to the increased risk of T2D and related
metabolic disturbances amongst Indian Asians compared to Europeans. Lastly I carried out a genome-wide association and replication study amongst 58,687 Indian Asian participants to identify
novel genetic factors in this ethnic group.
Results
The prevalence of T2D is ~4-fold higher amongst Indian Asians than Europeans, and is not accounted for by differences in adiposity and leisure time physical activity. In dietary studies, intake of fibre is inversely related to risk of insulin resistance among Indian Asians. However, major dietary
macronutrients do not account for differences in insulin resistance between
Indian Asians and Europeans. In genetic studies I demonstrate association of
25 previously reported T2D genetic variants with T2D amongst Indian Asians. Of the 48 T2D genetic variants examined, risk allele frequencies were similar and effect sizes lower amongst Indian Asians compared to Europeans; therefore known T2D genetic variants do not account for the increased
risk of T2D in this racial group. In the GWAS I discover 6 novel T2D genetic variants among Indian Asians (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and
HNF4A).
Conclusions
T2D has emerged as a major healthcare problem worldwide, with rates highest among individuals of Indian Asian descent. For the first time I discover six novel genetic susceptibility factors for T2D amongst Indian Asians. However, there is a ~4-fold higher risk of T2D among Indian Asians compared to Europeans, which remains largely unexplained.
Indian Asians are at increased risk of type-2 diabetes (T2D), insulin resistance and related
metabolic disturbances compared to Europeans. The contribution of known lifestyle and genetic risk
factors to the excess risk of T2D in Indian
Asians is not well understood.
Methods and materials
I investigated 16,774 Indian Asian and 7,301 European men and women participating in the in the London Life Sciences Population Study to determine the prevalence of T2D and related glycaemic disorders. I examined the contribution of adiposity, leisure time physical activity, major dietary macronutrients and known genetic susceptibility factors to the increased risk of T2D and related
metabolic disturbances amongst Indian Asians compared to Europeans. Lastly I carried out a genome-wide association and replication study amongst 58,687 Indian Asian participants to identify
novel genetic factors in this ethnic group.
Results
The prevalence of T2D is ~4-fold higher amongst Indian Asians than Europeans, and is not accounted for by differences in adiposity and leisure time physical activity. In dietary studies, intake of fibre is inversely related to risk of insulin resistance among Indian Asians. However, major dietary
macronutrients do not account for differences in insulin resistance between
Indian Asians and Europeans. In genetic studies I demonstrate association of
25 previously reported T2D genetic variants with T2D amongst Indian Asians. Of the 48 T2D genetic variants examined, risk allele frequencies were similar and effect sizes lower amongst Indian Asians compared to Europeans; therefore known T2D genetic variants do not account for the increased
risk of T2D in this racial group. In the GWAS I discover 6 novel T2D genetic variants among Indian Asians (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and
HNF4A).
Conclusions
T2D has emerged as a major healthcare problem worldwide, with rates highest among individuals of Indian Asian descent. For the first time I discover six novel genetic susceptibility factors for T2D amongst Indian Asians. However, there is a ~4-fold higher risk of T2D among Indian Asians compared to Europeans, which remains largely unexplained.
Version
Open Access
Date Issued
2013-04
Date Awarded
2013-10
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Kooner, Jaspal
Chambers, John
Publisher Department
National Heart and Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)