Soluble human leukocyte antigen-g expression and glucose tolerance in subjects with different degrees of adiposity.
BACKGROUND
Type 2 diabetes mellitus (T2DM) and obesity are characterized by a low-grade inflammation, which might be related to the development of insulin resistance. Human leukocyte antigen-G (HLA-G) shows antiinflammatory and tolerogenic properties, including the modulation of CD8+ T-cell cytotoxicity and regulation of CD4+ T-lymphocyte function. These functions are partially shared with IL-10, whose levels are reduced in insulin-resistant states.


OBJECTIVE
The aim was to explore the relationship between HLA-G and the metabolic and inflammatory pattern of obesity or T2DM.


METHODS
Soluble HLA-G, IL-6, and IL-10 were measured and related with metabolic and biochemical parameters in 230 volunteers with normal glucose tolerance, impaired glucose tolerance, or T2DM by oral glucose tolerance test.


RESULTS
sHLA-G, detected in 144 subjects (sHLA-G positive), was more frequent in T2DM or impaired glucose tolerance subjects than in normal glucose tolerance (chi(2) =18.6; P < 0.0001), and its plasma levels increased progressively across the classes of glucose tolerance. sHLA-G-positive individuals had higher body mass index, systolic blood pressure, and cholesterol levels; a reduced degree of insulin sensitivity; and almost 2-fold higher levels of IL-6, a cytokine related to insulin sensitivity, whereas IL-10 was similar. In the sHLA-G-positive subgroup, by a multivariate regression model, sHLA-G was significantly related to 2-h glucose, the area under insulin curve, and IL-6 levels (multiple r(2) = 0.14; P < 0.001), independently of age, gender, and body mass index.


CONCLUSIONS
A frequent expression of sHLA-G, linked to a typical biomarker of insulin resistance like IL-6, seems to characterize subjects with an impaired glucose metabolism.
Solini
Anna
A
Department of Internal Medicine, University of Pisa, Via Roma 67, I-56100 Pisa, Italy. a.solini@med.unipi.it
Muscelli
Elza
E
Stignani
Marina
M
Melchiorri
Loredana
L
Santini
Eleonora
E
Rossi
Chiara
C
Astiarraga
Brenno Domingues
BD
Rizzo
Roberta
R
Baricordi
Olavio Roberto
OR
D050154:Adiposity / Q000502:physiology*; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006680:HLA Antigens / Q000097:blood*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D012044:Regression Analysis; D018709:Statistics, Nonparametric
D015415:Biomarkers; D001786:Blood Glucose; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D015850:Interleukin-6; D016753:Interleukin-10