Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance

• Published in: Metabolism, clinical and experimental Vol. 63; no. 4; pp. 492 - 501
• Main Authors: van Beek, Lianne, Lips, Mirjam A, Visser, Annemieke, Pijl, Hanno, Ioan-Facsinay, Andreea, Toes, René, Berends, Frits J, Willems van Dijk, Ko, Koning, Frits, van Harmelen, Vanessa
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2014; Elsevier
• Subjects: Adipose tissue; Adipose Tissue - physiopathology; Biological and medical sciences; Crown like structures; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Endocrinology & Metabolism; Fatty acids; Fatty Acids, Nonesterified - blood; Feeding. Feeding behavior; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Glucose Tolerance Test; Glycerol - blood; Humans; Hypoglycemic Agents - therapeutic use; Interleukin-6 - blood; Lymphocyte Count; Lymphocytes; Medical sciences; Metabolic diseases; Middle Aged; Obesity; Obesity - blood; Obesity - complications; Obesity - physiopathology; Systemic inflammation; Systemic Inflammatory Response Syndrome - blood; Systemic Inflammatory Response Syndrome - complications; Systemic Inflammatory Response Syndrome - physiopathology; T-Lymphocyte Subsets; Vertebrates: anatomy and physiology, studies on body, several organs or systems; FFA; low density lipoprotein; crown like structures; C-reactive protein; Adipose tissue; IHC; cluster of differentiation; CLS; phorbol myristate acetate; IMDM; HDL-C; IFN-γ; Iscove’s modified Dulbecco’s medium; FSC; interferon gamma; IL; type two diabetes mellitus; body mass index; high density lipoprotein cholesterol; PBMC; Fatty acids; normal glucose tolerance; radioimmunoassay; NGT; Phytohaemagglutinin; Systemic inflammation; CRP; T2DM; PHA; Sideward scatter; tumor necrosis factor alpha; LDL; Lymphocytes; immunohistochemistry; interleukin; homeostasis model assessment; BMI; IRMA; CD; SSC; PMA; RIA; triglycerides; TG; TNF-α; free fatty acid; HOMA; Forward scatter; peripheral blood mononuclear cell; immunoradiometric assay; Crown like structures; Human; Obesity; Nutrition disorder; Tolerance; Female; Inflammation; Disseminated; Glucose; Woman; Endocrinology; Nutritional status
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2013.12.002

Abstract Introduction Obesity is strongly related to type-2 diabetes (T2DM), but there is a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy. This study determined to what extent differences in metabolic health in obese women are associated with differences in adipose tissue and/or systemic inflammation. Methods The subject group consisted of age comparable lean (n = 12) and obese women either with T2DM (n = 28) or normal glucose tolerance (NGT; n = 26). Number of crown like structures (CLS) and adipocyte size were measured in subcutaneous and visceral adipose tissue of the obese women. Circulating cytokine and free fatty acid (FFA) levels, as well as number and activation status of peripheral leukocytes were determined. Results Obese T2DM subjects showed higher circulating levels of IL-6, FFA and glycerol as compared to obese NGT subjects. Obese T2DM subjects had higher absolute numbers of peripheral leukocytes which were mainly due to an increase of T helper cells. Activation status of circulating cytotoxic T (CD8+CD25 +) and B (CD19+CD38 +) cells was significantly increased in obese NGT subjects as compared to lean but was not different between the two obese groups. Subcutaneous adipose tissue of obese T2DM subjects contained more CLS than adipose tissue of obese NGT subjects. Conclusion Obese T2DM subjects show higher FFA levels and adipose tissue macrophage infiltration in addition to higher levels of circulating IL-6 and numbers of CD4 + T cells than obese NGT subjects. Hence, obese T2DM subjects show a higher extent of inflammation at both the systemic and adipose tissue level.