Ryan Christopher M, Freed Martin I, Rood Julie A, Cobitz Alexander R, Waterhouse Brian R, Strachan Mark W J
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Diabetes Care. 2006 Feb;29(2):345-51. doi: 10.2337/diacare.29.02.06.dc05-1626.
The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance.
This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery.
Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1-2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG.
Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.
本研究的目的是确定代谢控制的改善是否能改善与2型糖尿病相关的认知功能障碍，并评估这种改善是否由循环胰岛素或胰岛素抵抗的变化介导。
这项随机双盲试验在美国18个中心招募了145名受试者。接受二甲双胍单药治疗的老年2型糖尿病患者接受罗格列酮（一种噻唑烷二酮类胰岛素增敏剂）或格列本脲的附加治疗。在基线和第24周使用数字符号替换测试、雷伊听觉词语学习测试和剑桥神经心理测试自动成套系统评估认知功能。
两组治疗前空腹血糖（FPG）相似，24周后两个治疗组的FPG均有相似的显著降低（2.1 - 2.3 mmol/l）。罗格列酮（P < 0.001）和格列本脲（P = 0.017）治疗后工作记忆均有改善。在配对联想学习测试中改善最为明显（错误减少25 - 31%），并且与FPG测量的血糖控制改善显著相关（r = 0.30）。
罗格列酮和格列本脲治疗均观察到相似且具有统计学意义的认知改善，且这种效果的程度与FPG改善程度相关。这些结果表明，针对血糖控制的药物干预可实现认知益处。
