The pathogenetic role of ghrelin and leptin in the comorbid course of gastroesophageal reflux disease and type 2 diabetes

Objective — to study the levels of ghrelin and leptin, depending on the body mass index (BMI) in patients with gastroesophageal reflux disease (GERD) against the background of type 2 diabetes mellites (T2DM), to determine their role in the GERD formation and progression against T2DM background and to build a prognostic model for the GERD development in presence of T2DM. Materials and methods. Examinations involved 120 patients (44 (44%) men and 56 (56%) women) who were divided into 3 groups: 1st group included 60 patients with comorbid GERD and T2DM, the 2nd group consisted of 20 patients with isolated GERD, and the 3rd group — 20 patients with T2DM. The control group consisted of 20 age‑matching practically healthy persons. The levels of ghrelin and leptin were determined by enzyme‑linked immunosorbent assay (ELISA) on a Labline‑90 analyzer (Austria). Results. Patients of the 2nd group demonstrated significantly maximal ghrelin levels 1.54±0.36 ng/mL, and leptin levels were significantly highest in the 1st group 18.87±1.22 ng/mL. Patients of the 1st group with a BMI ≥ 30 kg/m2 had higher values of serum leptin 25.34±1.51 ng/mL and lower values of ghrelin 0.65±0.02 ng/mL (р <0.001) when compared with subjects with normal or slightly excessed body weight. In patients of both 1st and 2nd groups, the correlation between BMI and leptin levels was significant, direct and strong (ρ=+0.89016 and ρ=+0.82493, respectively), that is, with an increase in the serum leptin levels, an increase in BMI should be expected. Dependence of BMI from ghrelin levels was significant, inverse, of medium strength (ρ=–0.6864 and ρ=–0.6635). In group 3 patients, significantly strong direct correlation between BMI and leptin (ρ=0.935245) and significantly strong inverse correlation between BMI and ghrelin (ρ=–0.7740) were found. A prognostic model of GERD development against T2DM background has been built, which considered the following parameters: levels of ghrelin, leptin, glycosylated hemoglobin, insulin resistance index (NOMA‑IR), BMI and the level of very low‑density lipoprotein cholesterol. According to the formula, the diagnosis of GERD is positive if Y >0.5 and negative if Y <0.5. According to the ROC analysis, it was established that the sensitivity of the obtained prognostic formula was 96.2%; specificity 75.0%. Conclusions. The obtained data showed that ghrelin and leptin play an important role in the formation and progression of GERD against T2DM background, and changes in the levels of these adipocytokines are among the factors that significantly complicate the clinical course of GERD and T2DM. Therefore, further studies are needed to determine whether leptin and ghrelin play a causal role in this relationship, or whether they are, after all, circulating biomarkers that improve insulin sensitivity and have anti‑inflammatory effects.