LAUSR

BACKGROUND The CDKAL1 (CDK5 Regulatory Subunit Associated Protein 1 Like 1) gene encodes cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated proten1 like 1. This protein has been shown to contribute to the glucose-dependent regulation of insulin secretion in pancreatic islets. AIMS The aim of our study was to analyze the effects of the rs7756992 genetic variant of CDKAL1 gene on fasting glucose and insulin resistance after weight loss secondary to partial meal replacement hypocaloric diet (pMRHD). METHODS This was a non-randomized, single-treatment study with a formula-diet in 44 obese subjects. The patients received nutritional education and a modified diet with two intakes of a normocaloric hyperproteic formula for 3-months. Anthropometric parameter and biochemical profile were measured at basal time and after 3 months. The variant of CDKAL1 gene rs7756992 was assessed. RESULTS The following genetic distribution was observed; [27AA (61.3%), 12 AG (27.3%) and 5 GG (11.4%)]. After the pMRHD, body weight, the body mass index (BMI), fat mass, waist circumference and blood pressure decreased in both genotypes. Non-G allele carriers showed a significant improvement in fasting glucose levels (AA vs. AG + GG) (-6.1 ± 1.4 md/dl vs. -1.2 ± 0.7 mg/dl; p = 0.01), fasting insulin levels (-3.6 ± 0.2 mU/l vs. -1.3 ± 0.6 mU/l; p = 0.02) and HOMA-IR (-1.2 ± 0.2 units vs. -0.3 ± 0.2 units; p = 0.01). Fasting plasma glucose levels were higher in G allele carriers than non G allele carriers. CONCLUSIONS Our data suggest that the genetic variant (rs7756992) of CDKAL1 gene is associated with glycaemic status after a pMRHD, with greater improvements in fasting glucose, insulin and HOMA-IR in subjects without the G allele.