The analysis of in vitro transforming growth factor-beta1 (TGF-beta1) production by peripheral blood in overt and pre-clinical type 1 diabetes mellitus.
The alterations of TGF-beta1 production are believed to contribute to the development of insulin-dependent diabetes mellitus (IDDM) in animal models as well as in humans. There is also increasing evidence about the role of this cytokine in the pathogenesis of diabetic vascular complications. The aim of our study was to evaluate in vitro TGF-beta1 production by peripheral blood of newly diagnosed type 1 diabetes patients and subjects in the pre-clinical stage of the disease in comparison to healthy controls and relatives of IDDM patients with low genetic risk for diabetes development. The study was carried out in three groups of subjects: 22 patients with a recently diagnosed type 1 diabetes, their 24 first degree relatives with a different genetic risk of IDDM development and 18 healthy volunteers (control group). In all studied groups whole blood was taken for morphology parameters. HbA1C and for 72 h cultures with PHA stimulation for the estimation of TGF-beta1 in vitro production. TGF-beta1 concentration in supernatants were quantified by ELISA. In the first degree relatives HLA typing (for DR3, DR4 and DQB1*0602 alleles), measurements of anti-pancreatic antibodies (ICA, GADA, IA-2A, IAA) and intravenous glucose tolerance tests were performed. The levels of TGF-beta1 in the supernatants were significantly higher in diabetic patients (P < 0.0002) and in their first degree relatives (P < 0.05) in comparison to the control group. In the group of first degree relatives TGF-beta1 levels were highest in subjects with the presence of two or more pancreatic autoantibodies and/or with impaired insulin release in IVGTT, but lowest in relatives with protective DQB1*0602 alleles (P < 0.01). There was also a significant positive correlation between the TGF-beta1 levels and HbA1C in the IDDM subjects and first degree relatives (P < 0.03). Our study suggests that the alterations of TGF-beta1 levels could be associated with the activity of autoimmune process leading to pancreatic B cells destruction and may have a role in the pathogenesis of diabetic complications, but further studies in humans are needed.
Kretowski
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Department of Endocrinology, Medical Academy of Bialystok, Poland. akretows@amb.ac.bialystok.pl
Maciej
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Ida
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D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D005951:Glucose Tolerance Test; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000276:immunology; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood*
D001323:Autoantibodies; D006681:HLA-D Antigens; D016212:Transforming Growth Factor beta