Ghrelin deficiency is associated with obesity, adipose tissue dysfunction and glucose variability in type 2 diabetes V.V. Klimontov, A.I. Korbut, O.N. Fazullina, D.M. Bulumbaeva, N.B. Orlov Scientific Institute of Clinical and Experimental Lymphology, Novosibirsk, Russia Background and aims: Ghrelin, a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract, plays an important role in regulation of feeding behavior and energy balance. It has been proposed that ghrelin is involved in development of adiposity and insulin resistance. The significance of ghrelin as a possible contributor to metabolic disturbances in diabetic patients remain to be clarified. In this study we aimed to determine the relationships between serum levels of ghrelin, adipokines, body fat distribution, and glucose variability in type 2 diabetic subjects. Material and methods: We observed 124 patients with type 2 diabetes, 48M/76F, 43-70 years of age (median 62 years), including 42 non-obese subjects and 82 patients with obesity. Twenty six non-obese healthy subjects matched by age and sex were acted as control. The concentrations of C-peptide, glucagon, ghrelin, leptin, resistin, visfatin, adipsin, adiponectin in the fasting serum were determined by Multiplex analysis. The fat mass and adipose tissue distribution was studied with dual-energy X-ray absorptiometry. The parameters of glucose variability, including standard deviation (SD), mean amplitude of glucose excursions (MAGE), 2-hour continuous overlapping net glycemic action, M-value, J-index, and mean absolute glucose, were derived from continuous glucose monitoring. Results: The levels of ghrelin in patients with diabetes were decreased significantly as compared to control (p<0.000001). Diabetic patients with obesity demonstrated lower ghrelin concentrations then non-obese patients (p=0.002). The levels of ghrelin correlated negatively with body mass index, proportion of fat mass and gynoid fat mass (r =-0.42, r =-0.42 and r =-0.49 respectively, all p<0.001). At the same time, there was a positive concentration between ghrelin concentration and lean mass (r=0.32, p=0.0003). In patients with diabetes significant increase in the levels of glucagon (p<0.0001), leptin (p=0.004), resistin (p<0.0001), adipsin (p<0.0001) and visfatin (p=0.0003) was revealed. Ghrelin levels demonstrated negative correlations with concentrations of glucagon, resistin and visfatin (r=-0.46, r=-0.48 and r=-0.45 respectively, all p<0.0001). We found positive correlations between ghrelin levels and nocturnal parameters of glucose variability: SD and MAGE (r=0.46 and r=0.62, both p<0.01). There were no correlations between the levels of ghrelin and other glucose variability parameters, mean monitored glucose, and HbA1c. Conclusion: Patients with type 2 diabetes are characterized by reduced serum level of ghrelin at fasting. The reduction in ghrelin concentrations in these patients is associated with obesity, adipose tissue dysfunction and nocturnal glucose variability.
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