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Serum adipokine concentrations in patients with type 2 diabetes: the relationships with distribution, hypertrophy and vascularization of subcutaneous adipose tissue

Abstract

Academy of Sciences, Novosibirsk, Russia 2Novosibirsk State Medical University, Novosibirsk, Russia


BACKGROUND: Adipose tissue (AT) dysfunction plays an important role in metabolic disorders in obesity and type 2 diabetes. The role of distribution, hypertrophy and vascularization of AT in adipokine secretion disturbances remain to be clarified.


AIMS: To determine the relationships between serum concentrations of adipokines and the mass and distribution of AT, diameter of adipocytes and vascularization of subcutaneous AT in patients with type 2 diabetes.


MATERIALS AND METHODS: A total of 125 patients were examined, including 82 subjects with obesity. Thirty persons without diabetes and obesity, matched by sex and age, were acted as control. Concentrations of leptin, resistin, visfatin, adipsin and adiponectin in fasting serum were determined using multiplex analysis. Mass and distribution of AT was assessed by dual-energy X-ray absorptiometry. Samples of SAT were obtained from umbilical region using a knife biopsy in 25 patients and in 15 individuals who died in accidents. Blood and lymphatic vessels in SAT were revealed with immunohistochemistry, using antibody to CD-34 and podoplanin respectively. The volume and numerical density, ultrastructure of blood and lymphatic vessels, and mean diameter of subcutaneous adipocytes were evaluated.


RESULTS: Patients with diabetes, as compared to control, had significantly higher levels of leptin, resistin, adipsin and visfatin (all p<0.001). Adiponectin showed no differences. Concentrations of leptin, resistin, visfatin, adipsin and adiponectin correlated positively with gynoid fat mass. Additionally, leptin and adipsinshowed positive correlations with truncal and central abdominal fat mass. Concentration of leptin, but not other adipokines, was associated with hypertrophy of subcutaneous adipocytes. A decrease in volumetric density of microvessels(р=0.01) and increase in volume and numerical density of lymphatic vessels (both р=0.02) was observed in subcutaneous AT from diabetic subjects. The swelling of cytoplasm, mitochondria, cisterns of granular endoplasmic reticulum and reduced content of micropinocytotic vesicles was revealed in lymphatic capillaries. Resistin and visfatin showed inverse associations with density of microvessels.


CONCLUSION: Endocrine dysfunction of AT in patients with type 2 diabetes, manifested by elevation of serum concentrations of leptin, resistin, visfatin and adipsin, is associated with mass and distribution of AT, hypertrophy of subcutaneous adipocytes and vascularization abnormalities of subcutaneous AT.

About the Authors

Vadim V. Klimontov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Novosibirsk State Medical University
Russian Federation

MD, PhD, Professor



Dinara M. Bulumbaeva
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Junior research associate



Nataliya P. Bgatova
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

PhD, Professor



Iuliia S. Taskaeva
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, Junior research associate



Nikolay B. Orlov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, PhD, Senior research associate



Olga N. Fazullina
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, Junior research associate



Michael Y. Soluyanov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, PhD, Senior research associate



Sergey V. Savchenko
Novosibirsk State Medical University
Russian Federation

MD, PhD, Professor



Vladimir I. Konenkov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

MD, PhD, Professor, Academician of the Russian Academy of Sciences



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Supplementary files

1. Fig. 1. Research design.
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2. Fig. 2. Schematic representation of the assessment of the distribution of adipose tissue by region in the Body Composition program. 1 - area android fat; 2 - region of gynoid fat.
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3. Fig. 3. Visualization and density of lymphatic vessels in subcutaneous adipose tissue in patients with type 2 diabetes mellitus and in control. A - the lymphatic vessel is normal; B - lymphatic vessels in a patient with type 2 diabetes. Immunohistochemical staining for a marker of endotheliocytes of the lymphatic vessels, subplanin. SW x400; In - bulk density of lymphatic vessels, LDVv,%; G is the numerical density of the lymphatic vessels, LVDq, n; * - p <0.02 in comparison with the control group.
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4. Fig. 4. The ultrastructural organization of the endothelial cells of the lymphatic and blood vessels of the adipose tissue of patients with type 2 diabetes. A - endothelium of the lymphatic capillary is normal; B - endothelium of the lymphatic capillary of a patient with type 2 diabetes and obesity. Outgrowths and protrusions of the luminal and basal surfaces of the endothelial cell of the lymphatic capillary. Contact with an adjacent endothelial cell (arrows); In - the endothelium of the blood capillary is normal; G - endothelium of the blood capillary of a patient with type 2 diabetes mellitus and obesity. Swelling of the cytoplasm of endotheliocytes, a decrease in the content of cytoplasmic organelles and vesicles. Electron microscopy. SW x10,000.
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5. Климонтов_Адипокины_Фото 5
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6. Климонтов_Адипокины_Фото 6
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7. Fig. 1. Study design.
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Klimontov V.V., Bulumbaeva D.M., Bgatova N.P., Taskaeva I.S., Orlov N.B., Fazullina O.N., Soluyanov M.Y., Savchenko S.V., Konenkov V.I. Serum adipokine concentrations in patients with type 2 diabetes: the relationships with distribution, hypertrophy and vascularization of subcutaneous adipose tissue. Diabetes mellitus. 2019;22(4):336-347. (In Russ.)

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ISSN 2072-0351 (Print)
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