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AIMTo study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease (NAFLD) in db/db mice.METHODSMale diabetic db/db mice (BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin (10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) was assessed by immunohistochemistry.RESULTSIn 18-wk-old diabetic mice, liver steatosis (predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets (92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets (20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independent to changes in the plasma glucose levels.CONCLUSIONThe DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice.

Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and the risk of complicationsKlimontov V.V., Myakina N.E. Institute of Clinical and Experimental Lymphology, Novosibirsk, Russian Federation The routine approach to evaluating the effectiveness of diabetes treatment based on the level of glycated haemoglobin (HbA 1c ) accounts for the average glucose level but does not consider the scope and frequency of its fluctuations. The development of computational methods to analyse glycaemic oscillations has made it possible to propose the concept of glycaemic variability (GV). The interest in research focused on GV increased dramatically after continuous glucose monitoring (CGM) technology was introduced, which provided the opportunity to study in detail the

Клинические и метаболические факторы, ассоциированные с хроническим воспалением низкой интенсивности, у больных сахарным диабетом 2 типа © Климонтов В.В., Тян Н.В., Фазуллина О.Н., Мякина Н.Е., Лыков А.П., Коненков В.И. (r=0,34, r=0,28 и r=0,31 соответственно, p<0,00004). Концентрация α1-AGP не показала связи с массой жировой ткани, но коррелировала со средним уровнем гликемии, CONGA,38, r=0,36, r=0,43 и r=0,4 соответственно, p<0,0001 (r = 0.34, r = 0.28 and r = 0.31; respectively, p < 0.00004). α1-AGP level showed no relationship with fat mass but positively correlated with mean glucose, CONGA, r = 0.36, r = 0.43 and r = 0.4; respectively, p < 0.0001). Patients with the highest hsCRP levels (>75 percentile) ФГБНУ Научно-исследовательский институт клинической и экспериментальной лимфологии, Новосибирск

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