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Background:Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated.The aim of this study was to investigate whether common variants in genes CDKAL1,HHEX,ADCY5,SRR,PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods:Twelve single nucleotide polymorphisms (rs7756992/rs 10946398 in CDKAL1,rs1 111875 in HHEX,rs391300 in SRR,rs17584499 in PTPRD,rs 1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals b in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays,of which 645 had normal glucose tolerance,181 had developed type 2 diabetes and 348 impaired glucose regulation.Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results:Birthweight was inversely associated with CDKAL1-rs10946398 (β =-41 g [95％ confidence interval [CI]:-80,-3],P =0.034),common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life.After adjusting for sex,gestational weeks,parity and matal age,the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β =-36 g [95％ CI:-72,-0.2],P =0.048).The risk allele in SRR showed a trend toward a reduction of birthweight (P =0.085).Conclusions:This study identified the association between type 2 diabetes risk variants in CDKALI and birthweight in Chinese Han individuals,and the carrier of risk allele within SRR had the trend of reduced birthweight.This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth,which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.