The expression of particular glucose transporters and insulin resistance indicators in the risk groups of type 2 diabetes - a two-year follow-up

Introduction: The proper expression of particular glucotransporter (GLUT) isoforms determines a sufficient supply of glucose to tissues. The impairment of cellular glucose transport observed in insulin resistance leads to glucose metabolism disturbances. The aim of this study was the estimation of insulin resistance indicators and the quantitative expression of GLUT-1, GLUT-3 and GLUT-4 on peripheral blood lymphocytes in prediabetic subjects and persons with a positive family history of type 2 diabetes during 24 months of observation. Material and methods: The study included 25 prediabetic subjects (according to WHO criteria) and 24 normoglycaemic individuals with a positive family history of type 2 diabetes. Twenty three healthy subjects with no family history of type 2 diabetes, matched with BMI, served as a control group. All participants were recommended to perform physical activity for at least 140 minutes per week and to maintain a low calorie diet. The peripheral blood lymphocytes demonstrating expression of GLUT-1, GLUT-3 and GLUT-4 were labelled with the use of indirect immunofluorescence. The expression of GLUT isoforms was investigated by flow cytometry. Cells were stained by using anti-human GLUT antibodies and FITC-conjugated immunoglobulin. Flow cytometry was performed using a FACS Calibur (Becton-Dickinson). Additionally, we determined: fasting plasma glucose (FPG), insulin and C peptide concentrations, HOMA-IR, BMI and WHR. All the tests were performed at baseline, and after 12 and 24 months. Results: At baseline, prediabetics and subjects with a positive family history of type 2 diabetes were characterised by a much higher expression of GLUT-4 compared to control subjects. Twenty four months of lifestyle modification resulted in significant lowering of the expression of GLUT-4 on the surface of PBL in both studied groups, with no differences in the expression of GLUT-1 or GLUT-3. Both prediabetic subjects and individuals with a positive family history of type 2 diabetes revealed no significant differences in determined insulin resistance markers after 24 months of the observation compared to the baseline values. Conclusions: The estimation of typical GLUT isoforms present on the peripheral blood lymphocytes, as well as the evaluation of insulin resistance indicators, are obviously insufficient for monitoring the metabolic disorders progression in the risk groups of type 2 diabetes. The decrease in GLUT-4 lymphocyte expression may reflect a positive influence of lifestyle modification on a tissue redistribution of this crucial insulin-dependent glucotransporter. The determination of GLUT-4 on the surface of peripheral blood lymphocytes can be a useful tool for the evaluation of the efficacy of therapeutic actions in subjects at high risk of type 2 diabetes. (Pol J Endocrinol 2012; 63 (3): 212-219)