A study to investigate genetic factors associated with weight gain in people with diabetes: analysis of polymorphisms in four relevant genes.

Background: Weight change is often seen in people with diabetes. We investigated the effects of genes associated with weight change/glucose handling/insulin-signalling.

Materials/methods: DNA from diabetes individuals and non-diabetes individuals, plus clinical data, were available from the DARE study ( = 379 individuals: T1D  = 111; T2D  = 222; controls  = 46). Weight gain was assessed by temporal change of Body Mass Index (BMI). Genotyping was performed for rs926198, rs1137101, rs6265 and rs9939609.

Results: No differences in genotype distributions were observed for the four SNPs in all groups un-stratified by weight gain. Following stratification differences in genotype distribution were observed. For those BMI relatively stable; controls showed a difference in genotype distributions versus T1D (rs926198, rs1137101). In T2D vs controls, significant differences were observed in genotype distribution for all four genes. For BMI increase, the only difference by category was rs1137101 (bothT1D/T2D vs controls). In BMI-stable groups, rs926198, T1D individuals showed lower T allele frequency (=0.004) vs non-diabetes and for rs1137101 a higher G allele frequency versus controls (=0.002). For T2D, rs926198, T allele frequency was lower in T2D than controls (=0.005). For rs1137101, the G allele frequency was higher than in controls (=0.004). In those with BMI increase, rs1137101 T1D individuals had higher G allele frequency versus controls (=0.002) as did T2D vs controls (=0.03).

Conclusion: Differences in allele frequency were seen between diabetes individuals and non-diabetes diagnosed at baseline in relation to the likelihood of BMI increase of >10%. It is established that the G allele of rs1137101 is associated with weight gain/obesity. However, this is the first report of rs926198 polymorphism being associated with weight stability/gain in diabetes.