TY - JOUR

T1 - Physiologic characterization of type 2 diabetes-related loci

AU - Grarup, Niels

AU - Sparsø, Thomas

AU - Hansen, Torben

PY - 2010/12/1

Y1 - 2010/12/1

N2 - For the past two decades, genetics has been widely explored as a tool for unraveling the pathogenesis of diabetes. Many risk alleles for type 2 diabetes and hyperglycemia have been detected in recent years through massive genome-wide association studies and evidence exists that most of these variants influence pancreatic ß-cell function. However, risk alleles in five loci seem to have a primary impact on insulin sensitivity. Investigations of more detailed physiologic phenotypes, such as the insulin response to intravenous glucose or the incretion hormones, are now emerging and give indications of more specific pathologic mechanisms for diabetes-related risk variants. Such studies have shed light on the function of some loci but also underlined the complex nature of disease mechanism. In the future, sequencing-based discovery of low-frequency variants with higher impact on intermediate diabetes-related traits is a likely scenario and identification of new pathways involved in type 2 diabetes predisposition will offer opportunities for the development of novel therapeutic and preventative approaches.

AB - For the past two decades, genetics has been widely explored as a tool for unraveling the pathogenesis of diabetes. Many risk alleles for type 2 diabetes and hyperglycemia have been detected in recent years through massive genome-wide association studies and evidence exists that most of these variants influence pancreatic ß-cell function. However, risk alleles in five loci seem to have a primary impact on insulin sensitivity. Investigations of more detailed physiologic phenotypes, such as the insulin response to intravenous glucose or the incretion hormones, are now emerging and give indications of more specific pathologic mechanisms for diabetes-related risk variants. Such studies have shed light on the function of some loci but also underlined the complex nature of disease mechanism. In the future, sequencing-based discovery of low-frequency variants with higher impact on intermediate diabetes-related traits is a likely scenario and identification of new pathways involved in type 2 diabetes predisposition will offer opportunities for the development of novel therapeutic and preventative approaches.

KW - Animals

KW - Diabetes Mellitus, Type 2

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin Resistance

KW - Insulin-Secreting Cells

U2 - 10.1007/s11892-010-0154-y

DO - 10.1007/s11892-010-0154-y

M3 - Journal article

C2 - 20886378

VL - 10

SP - 485

EP - 497

JO - Current Diabetes Reports

JF - Current Diabetes Reports

SN - 1534-4827

IS - 6

ER -