Increased secretion of TGF-beta1 by peripheral blood mononuclear cells from patients with Type 1 diabetes mellitus with diabetic nephropathy.
OBJECTIVE
To study transforming growth factor (TGF)-beta1 secretion by peripheral blood mononuclear cells (PBMC) from Type 1 diabetic patients with and without nephropathy.


METHODS
Thirty normoalbuminuric Type 1 diabetic patients (urinary albumin excretion rate (AER) < 20 microg/min), 12 microalbuminuric (AER 20-200 microg/min), 10 nephropathic (AER > 200 microg/min), and 13 non-diabetic individuals were recruited. TGF-beta1 secretion by PBMC was measured by enzyme immunoassay (EIA) after 48 h culture with and without phytohaemagglutinin (PHA) (5 microg/ml).


RESULTS
After 48 h culture, the highest TGF-beta1 levels secreted by unstimulated PBMC were found in patients with nephropathy (median 6.2 (range 0.9-20.0) ng/ml) when compared to patients with normal albumin excretion (4.1 (0.2-11.3) ng/ml), microalbuminuria (1.8 (0.2-6.4) ng/ml) and healthy controls (1.0 (0.2-7.0) ng/ml); P = 0.02 for the three diabetic groups and P = 0.006 for all groups. At 48 h, the PHA-stimulated TGF-beta1 levels were 12.4 (2.9-30.0) ng/ml in nephropathic, 7.3 (0.5-21.2) ng/ml in normoalbuminuric, and 5.5 (0.5-27.6) ng/ml in microalbuminuric patients (P = 0.05). A correlation was observed between TGF-beta1 and diastolic blood pressure in the subgroup of patients with incipient and overt nephropathy (r = 0.45, P = 0.04).


CONCLUSIONS
Type 1 diabetic patients with overt nephropathy show increased TGF-beta1 secretion by PBMC. Diastolic blood pressure levels correlated with TGF-beta1 secretion in diabetic patients with nephropathy. Increased TGF-beta1 secretion by PBMC may be associated with renal and vascular disease in Type 1 diabetes mellitus.
Korpinen
E
E
Hospital for Children and Adolescents, University of Helsinki, Finland. eija.korpinen@hus.fi
Groop
P H
PH
Fagerudd
J A
JA
Teppo
A M
AM
Akerblom
H K
HK
Vaarala
O
O
D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood* / Q000652:urine; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000097:blood*
D015415:Biomarkers; D016212:Transforming Growth Factor beta