糖尿病的胚胎论主要包括节俭基因论和节俭表型论。本研究将选取1000名于1959-1961年大饥荒期间出生的并出生于饥荒较重的农村地区的人群作为暴露组，匹配1000名同性别出生于同一地区的1963年的人群作为对照组。测试目前全基因组关联分析发现的出生体重基因SNPs和亚洲人群糖尿病基因SNPs。结合已经收集到的信息，（1）将首次研究出生于饥荒时期的人群是否携带低出生体重基因和糖尿病基因的比例更高；（2）探讨在中国人群中，哪些基因与饥荒对糖尿病的交互作用更明显；（3）在其52岁左右的时候，饥荒是否已经显著影响到其胰岛功能损伤及糖尿病的危险性，以及该危险性是否依赖于后天不健康的生活方式；（4）还将首次研究低出生体重基因和糖尿病基因与后天不健康的生活方式的关联性在饥荒期间出生的人群中是否更强。研究结果对于探讨糖尿病的发病机制具有非常重要的意义，也将对我国糖尿病的预防策略的制定提供理论依据。

Fetal origin hypothesis of diabetes is developed from the thrifty genotype hypothesis and thrifty phenotype hypothesis. The overall objective of the proposed study is to test the hypothesis of thrifty genotype and thrifty phenotype on risk of type 2 diabetes, using Chinese famine as a quasi-experimental exposure. We will select 1000 participants who were born in the rural and severe famine area during 1959-1961 as famine exposed group, and matched by 1000 participants by sex and born area who were born in 1063 as control group. The SNPs identified by the recent GWAS for birth weight and diabetes among Asian people will be measured. Our specific aims include: (1) to compare the risk allele frequency of the birth weight and diabetes SNPs between famine exposed and control group; (2) to explore the interaction between gene and famine exposure on risk of type 2 diabetes; (3) to explore the interaction between gene and unhealthy lifestyle as adult on risk of type 2 diabetes; (4) to examine the interaction between gene and unhealthy lifestyle as adult on risk of type 2 diabetes, and compare their difference between famine exposed and control group. The finding would provide valuable evidence for the fetal origin hypothesis of type 2 diabetes, and then provide support for the prevention strategy development.