Endocrine Abstracts

Introduction: The shape of the glucose curve during oral glucose tolerance test (OGTT) reflects the dynamic of the glucose stimulus-response, and it can be considered as predictor of the impaired glucose tolerance and Type 2 Diabetes (T2D). Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. Due to the fact that obesity and T2D are common in several ciliopathies, we enrolled this gene into the candidate genes for impaired glucose tolerance and T2D. Previously, we have confirmed the relationship between the gene for NME7 and the parameters associated with T2D and obesity on a large set of DNAs from the Czech population.

Aim: The aim of the study was to ascertain possible association of the OGTT glucose curves with the genetic background.

Methods: The study included 1219 3-h OGTT curves (blood collection in 30 min intervals) from 997 women (age median 32 years) and 222 men (age median 31 years) with a wide range of glucose tolerance. The OGTT glucose curves were divided accordingly to their shape into four groups: monophasic, biphasic, triphasic and curves with more than three peaks. In these groups we studied the variability of the candidate genes for glucose metabolism disturbances and related diseases: NME7, ATP1B1, BLZF1, GCK, KCNJ11, LRP5, PPARGC1A, PPARG, SLC30A8, TCF7L2, FTO, ZBTB16, THADA, PICALM, BIN1, CLU, CR1, MTNR1B, PNPLA3. The polymorphisms were genotyped using TaqMan SNP genotyping assays (RealTime LC480, Roche).

Results: Most of the OGTT glucose curves were monophasic (48.4%), then triphasic (26.7%), biphasic (20%), curves with more than three peaks were rare (4.9%). The monophasic curves were connected with worse metabolic profile (the lowest insulin sensitivity and insulin secretion, worse lipid spectrum). The shape of glucose OGTT curves was associated with NME7 polymorphisms (rs10732287, P=0.001; rs4264046, P=0.01; rs10800438, P=0.02) with the lowest frequencies of minor alleles in the biphasic type of curves.

Conclusion: The shape of glucose OGTT curves is variable and is connected with distinct metabolic profile. Our study found the association of the curve shape with the variability of the NME7 gene which biological function is still not clear. We are now preparing the animal nme7 knock-out model.

Supported by grants GACR 17-13491S, NV 18-01-00399, MH CR-DRO (EU 00023761).