Ebeling P, Teppo A M, Koistinen H A, Viikari J, Rönnemaa T, Nissén M, Bergkulla S, Salmela P, Saltevo J, Koivisto V A
Department of Medicine, Helsinki University Central Hospital, Finland.
Diabetologia. 1999 Dec;42(12):1433-8. doi: 10.1007/s001250051315.
AIMS/HYPOTHESIS: Inflammation could play a part in insulin resistance. Thiazolidinediones, new antidiabetic drugs, possess anti-inflammatory effects in vitro. We investigated if acute-phase serum proteins are increased in patients with Type II (non-insulin-dependent) diabetes mellitus who had been treated with insulin and whether troglitazone has anti-inflammatory effects in vivo.
A total of 27 patients (age 63.0+/-1.7 years, HbA1c 8.8+/-0.3%, BMI 32.7+/-0.8 kg/m2, duration 15.2+/-1.4 years, insulin dose 73.3+/-7.0 U/day) participated in the study. The patients received daily either 400 mg troglitazone or placebo for 16 weeks. Blood samples were taken at baseline, at the end of therapy and after a follow-up time of 23+/-4 days.
The concentrations of serum amyloid A (6.2+/-1.1 mg/l) and C-reactive protein (6.1+/-1.1 mg/l) were increased (p < 0.001) and complement protein C3 (1.69+/-0.05 g/l) was also above the reference range for healthy subjects. Placebo treatment had no effect on glucose or inflammation, whereas troglitazone reduced fasting glucose (from 10.4+/-0.6 mmol/l to 8.1+/-0.5 mmol/l, p < 0.01), HbA1c (from 8.7+/-0.3% to 7.5+/-0.3%, p < 0.01), insulin requirements (from 75+/-10 U/day to 63+/-10 U/day, p < 0.05), serum amyloid A (from 6.3+/-1.5 mg/l to 4.0+/-1.3 mg/l, p = 0.001), alpha-1-acid glycoprotein (from 906+/-51 mg/l to 729+/-52 mg/l, p = 0.001) and C3 (from 1.72+/-0.07 g/l to 1.66+/-0.06 g/l, p < 0.05) but not alpha-1-antitrypsin, ceruloplasmin, C-reactive protein or haptoglobin significantly. Concentrations of glucose and acute-phase reactants had returned to those before treatment at the follow-up visit.
CONCLUSION/INTERPRETATION: In Type II diabetic patients serum amyloid A and complement protein C3 are raised. Troglitazone exerts a selective reversible action on some acute-phase proteins and C3 but not on others in conjunction with the improvement in glucose metabolism.
目的/假设：炎症可能在胰岛素抵抗中起作用。噻唑烷二酮类新型抗糖尿病药物在体外具有抗炎作用。我们研究了接受胰岛素治疗的II型（非胰岛素依赖型）糖尿病患者急性期血清蛋白是否升高，以及曲格列酮在体内是否具有抗炎作用。
共有27名患者（年龄63.0±1.7岁，糖化血红蛋白8.8±0.3%，体重指数32.7±0.8kg/m2，病程15.2±1.4年，胰岛素剂量73.3±7.0U/天）参与研究。患者每天服用400mg曲格列酮或安慰剂，持续16周。在基线期、治疗结束时以及随访23±4天后采集血样。
血清淀粉样蛋白A（6.2±1.1mg/l）和C反应蛋白（6.1±1.1mg/l）浓度升高（p<0.001），补体蛋白C3（1.69±0.05g/l）也高于健康受试者的参考范围。安慰剂治疗对血糖或炎症无影响，而曲格列酮可降低空腹血糖（从10.4±0.6mmol/l降至8.1±0.5mmol/l，p<0.01）、糖化血红蛋白（从8.7±0.3%降至7.5±0.3%，p<0.01）、胰岛素需求量（从75±10U/天降至63±10U/天，p<0.05）、血清淀粉样蛋白A（从6.3±1.5mg/l降至4.0±1.3mg/l，p=0.001）、α-1-酸性糖蛋白（从906±51mg/l降至729±52mg/l，p=0.001）和C3（从1.72±0.07g/l降至1.66±0.06g/l，p<0.05），但对α-1-抗胰蛋白酶、铜蓝蛋白、C反应蛋白或触珠蛋白无显著影响。随访时血糖和急性期反应物浓度已恢复至治疗前水平。
结论/解读：II型糖尿病患者血清淀粉样蛋白A和补体蛋白C3升高。曲格列酮在改善糖代谢的同时，对某些急性期蛋白和C3具有选择性可逆作用，而对其他蛋白无此作用。
