2型糖尿病患者糖耐量正常一级亲属降脂治疗对胰岛B细胞功能的影响

Effect of lipid-lowering treatment on the function of B islet cells in the first-order relatives with normal glucose tolerance of type 2 diabetes mellitus

目的观察2型糖尿病患者糖耐量正常一级亲属血清游离脂肪酸(FFA)浓度降低后,胰岛B细胞分泌功能的变化。方法2004年4月至2005年7月,对安徽医科大学第一附属医院内分泌科38例2型糖尿病(T2DM)患者糖耐量正常的一级亲属,给予阿昔莫司0.25g,每日3次,口服,连用5d。服药前后均进行75g口服葡萄糖耐量试验(OGTT)。结果服用阿昔莫司后,空腹FFA、胰岛素抵抗指数(HOMA-IR)、OGTT葡萄糖曲线下面积(AUCg)、游离脂肪酸曲线下面积(AUCf)均明显降低(P<0.05或P<0.01),胰岛B细胞功能指数(ΔI30/ΔG30)、胰岛B细胞功能调整指数(ΔI30.ΔG30-1.HOMA-IR-1)均明显增加(P<0.05或P<0.01),而体重指数(BMI)、腰臀围比(WHR)、空腹血糖、空腹胰岛素、胰岛素曲线下面积(AUCi)均无显著改变(P>0.05)。服药前后ΔI30/ΔG30、ΔI30.ΔG30-1.HOMA-IR-1的改变值与空腹FFA改变值(ΔFFA)、AUCf改变值(ΔAUCf)呈显著负相关(r=-0.39^-0.49,P<0.05或P<0.01),HOMA-IR改变值(ΔHOMA-IR)与ΔFFA、ΔAUCf均呈显著正相关(r=0.31,0.35,P<0.05);服药前后AUCg改变值(ΔAUCg)与ΔI30/ΔG30、ΔI30.ΔG30-1.HOMA-IR-1的改变值呈显著负相关(r=-0.52,-0.56,P<0.01),与ΔHOMA-IR无显著相关性(r=0.28,P=0.07);ΔAUCg与ΔAUCf之间呈显著正相关(r=0.44,P<0.05)。结论阿昔莫司在降低T2DM患者糖耐量正常的一级亲属FFA的同时,可明显改善胰岛素敏感性、口服葡萄糖耐量以及胰岛B细胞的分泌功能,提示脂毒性可能参与早期胰岛B细胞功能缺陷的发生。

Objective To study the change of B-cell function after reduction in plasma free fatty acid（FFA） concentration. Methods All 38 normoglycemic first-degree relatives of type 2 diabetes received a 75 g oral glucose tolerance test （ OGTT）, before and after acipimox,250 mg orally rid for 5 days. Results Acipimox significantly reduced fasting plasma FFA,HOMA-IR, the incremental glucose area under the curve （AUCg）and the incremental FFA area under the curve （AUCf） during OGTT （ P 〈 0. 05 - 0. 01 ）, and significantly increased △I3o/△G30, △I30 · △G30^-1 . HOMA-IR^-1（ p 〈 0. 05-0. 01 ）;whereas following acipimox, body mass index, waist and hip circumference ratio, fasting plasma glucose, fasting insulin and the incremental insulin area under the curve（ AUCi ）during OGTT all did not change（ P 〉0. 05 ）. The increment in △I30/△G30 ,△I30 · △G30^-1 . HOMA-IR^-1 correlated negatively with the decrement in fasting FFA, AUCf（r = -0. 39 - -0. 49, P 〈 0. 05 - 0. 01 ）, whereas the decrement in HOMA-IR correlated positively with the decrement in fasting FFA, AUCf （ r = 0. 31,0. 35, P 〈 0. 05 ）. The decrement in AUCg correlated negatively with △I30/△G30 、 △I30·△G30^-1 · HOMA-IR^-1（r = -0. 52, -0. 56,P 〈 0. 01 ）, whereas it did not correlate with the decrement in HOMA-IR （ r = 0. 28 ,P = 0. 07 ）. There was significant positive correlation between the decrement in AUCg and AUCf. Conclusion The reduction in plasma free fatty acid after administration of acipimox can obviously improve insulin sensitivity ,oral glucose tolerance and islet B-cell function in normoglycemic first-degree relatives of type 2 diabetes suggesting lipotoxicity might be involved in early phase B-cell dysfunction.