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


CONCLUSIONS
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.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Lianne
L
van Beek
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden The Netherlands.
Mirjam A
MA
Lips
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Annemieke
A
Visser
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden The Netherlands.
Hanno
H
Pijl
Department of Rheumatology. Leiden University Medical Center, Leiden, The Netherlands.
Andreea
A
Ioan-Facsinay
Department of Rheumatology. Leiden University Medical Center, Leiden, The Netherlands.
René
R
Toes
Department of Surgery, Rijnstate Hospital, Arnhem, The Netherlands.
Frits J
FJ
Berends
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden The Netherlands.
Ko
K
Willems van Dijk
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Frits
F
Koning
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: V.J.A.van_Harmelen@lumc.nl.
Vanessa
V
van Harmelen
D000273:Adipose Tissue / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D018655:Lymphocyte Count; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D016176:T-Lymphocyte Subsets
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D005990:Glycerol
Adipose tissue; Crown like structures; Fatty acids; Lymphocytes; Systemic inflammation