Contribution of polymorphisms in the LEP, LEPR and RETN genes on serum leptin and resistin levels in young adults from Mexico.

Polymorphisms in the LEP (G-2548A and A19G), LEPR (A326G, A668G and G3057A) and RETN (C-420G and G+62A) genes were documented according to their association with alterations in biochemical parameters such as glucose, insulin and lipid profiles, along with serum leptin and resistin concentrations. The aim of the study was to establish any contribution of the G-2548A and A19G polymorphisms of the LEP gene, the A326G, A668G and G3057A polymorphisms of the LEPR gene, and the C-420G and G+62A polymorphisms of the RETN gene to serum leptin and resistin levels in Mexican young adults. Clinical and biochemical variables, serum leptin and resistin levels, and genotype profiles were analysed in 66 Mexican young adults. Seven polymorphisms in the LEP, LEPR and RETN genes were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analysis. Individuals carrying allele 3057A of the G3057A polymorphism in the LEPR gene showed significantly higher leptin concentrations than those bearing the genotype G/G (43.78 ± 39.11 vs 28.20 ± 14.12 ng/mL; p = 0.021). There were no associations of serum leptin or resistin levels according to the genotype of the other six analysed polymorphisms. Our results suggest that the allele 3057A of the LEPR G3057A polymorphism contributes to increased serum leptin levels in Mexican young adults.

Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by chronic hyperglycemia as a consequence of decreased insulin sensitivity, which contributes to bone demineralization and could also be related to changes in serum levels of osteocalcin and insulin, particularly when coupled with a deficiency in the daily consumption of vitamins D3 and K2. The objective of this study was to evaluate the effect of vitamin D3 and vitamin K2 supplements alone or in combination on osteocalcin levels and metabolic parameters in patients with T2DM. METHODS: A double-blind, randomized clinical trial was carried out in 40 patients aged between 30 and 70 years old for 3 months. Clinical and laboratory assessment was carried out at the beginning and at the end of the treatment. The patients were divided into three groups: (a) 1000 IU vitamin D3 + a calcinated magnesium placebo (n = 16), (b) 100 µg of Vitamin K2 + a calcinated magnesium placebo (n = 12), and (c) 1000 IU vitamin D3 + 100 µg vitamin K2 (n = 12). RESULTS: After treatment in the total studied population, a significant decrease in glycemia (p = 0.001), HOMA-IR (Homeostatic model assessment-insulin resistance) (p = 0.040), percentage of pancreatic beta cells (p < 0.001), uOC/cOC index and diastolic blood pressure (p = 0.030) were observed; in vitamin D3 group, differences in serum undercarboxylated osteocalcin (p = 0.026), undercarboxylated to carboxylated osteocalcin index (uOC/cOC) (p = 0.039) glucose (p < 0.001) and  % of functional pancreatic beta cells (p < 0.001) were demonstrated. In vitamin K2 group a significant decrease in glycemia (p = 0.002), HOMA-IR (p = 0.041), percentage of pancreatic beta cells (p = 0.002), and in cOC (p = 0.041) were observed, conversely cOC concentration was found high. Finally, in the vitamins D3 + K2 a significant decrease in glycemia (p = 0.002), percentage of pancreatic beta cells (p = 0.004), and in the uOC/cOC index (p = 0.023) were observed. CONCLUSION: Individual or combined supplementation with vitamins D3 and K2 significantly decreases the glucose levels and  % of functional pancreatic beta cells, while D3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. Only in the group with vitamin D3 supplementation, it was observed a reduction in undercarboxylated osteocalcin while vitamin K2 increased the carboxylated osteocalcin levels.Trial registration NCT04041492.