Endocrine Abstracts

Background: The fetal insulin hypothesis proposes that low birth weight, insulin resistance, and decreased insulin secretion in adulthood are genetically mediated. Babies with low birth weight have higher morbidity and mortality risk in adulthood. However, this situation could also occur in children with adequate weight at birth with genetic risk factors. The polymorphisms rs11708067 in ADCY5 and rs7754840 in CDKAL1 have been associated with low birth weight, risk of DM2, and lower insulin secretion in adults. However, it remains to be proven if they are related to fetal-neonatal insulin secretion or insulin resistance.

Methods: Genotyping for rs11708067 in ADCY5 was performed by RFLPS and for rs7754840 in CDKAL1 by qPCR with TaqMan probe in genomic DNA from 218 healthy neonates recruited in Guanajuato. Neonatal C-peptide and insulin concentrations were measured by ELISA. The difference between genotypes was evaluated using ANOVA. The association of polymorphisms with insulin and C-peptide was evaluated by multiple regression.

Results: Differences were found in the concentrations of insulin (P=0.010) and C-peptide (P=0.004) between rs11708067genotypes, with lower concentrations of both variables on allele A carriers. We found an inverse association of the A allele of rs11718067 with insulin (P=0.016) and neonatal C-peptide (P<0.001). No differences were found between genotypes and birth weight, glucose, or HOMA-IR. For rs7754840 no difference was found between genotypes for any variable, nor association with insulin concentrations or C-peptide.

Conclusions: The risk allele A in rs11708067 ADCY5 could be related to fetal/neonatal insulin secretion. This is the first study to evaluate neonatal insulin associated with the rs11708067 genotype. This proyect was supported by CONACYT (CB-2013-222563) and UG-DAIP 2016-2017 (1089/2016).