Given that type 2 diabetes mellitus is common in several ciliopathies, the NME7 gene (non-metastatic cells 7), encoding a recognized member of the ciliome, was studied in connection with glucose metabolism. The aim was to find out whether the variability in the gene is associated with the response to administered glucose during the 3 h oral glucose tolerance test. The study included 1262 individuals with different levels of glucose tolerance. Glycemic curves were categorized according to their shape as monophasic, biphasic, triphasic, and more complex multiphasic. The analysis showed a significant association of five linked NME7 polymorphisms with the biphasic course of the glycemic curve, a shape that has been shown to be metabolically protective. Specifically, minor alleles of rs4656659 and rs2157597 in combination with wild-type alleles of rs10732287, rs4264046, and rs10800438 were more frequent within the biphasic category. Moreover, haplotype analysis confirmed higher insulin sensitivity in carriers of this specific haplotype. In conclusion, a cluster of five linked NME7 polymorphisms showed an association with a biphasic glycemic curve. Considering the health benefits of the biphasic curve in terms of glycoregulation and taking into account the demonstrated link of the NME7 haplotype with insulin sensitivity, variability in the NME7 gene represents another piece of the complex mosaic influencing healthy energy processing.

2nd Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague Czech Republic

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University and General University Hospital Prague Albertov 4 128 00 Prague Czech Republic

Institute of Endocrinology Narodni 8 110 00 Prague Czech Republic

Institute of Neuroscience National Research Council Corso Stati Uniti 4 35127 Padova Italy

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