Morris Jill K, Vidoni Eric D, Mahnken Jonathan D, Montgomery Robert N, Johnson David K, Thyfault John P, Burns Jeffrey M
Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Alzheimer's Disease Center, University of Kansas Medical Center, Fairway, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Neurobiol Aging. 2016 Mar;39:19-24. doi: 10.1016/j.neurobiolaging.2015.11.005. Epub 2015 Dec 1.
Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important physiological differences between these cohorts.
胰岛素抵抗是阿尔茨海默病（AD）的一个风险因素，尽管其在AD病因学中的作用尚不清楚。我们在51名无痴呆（ND；n = 37）和有认知障碍（CI；n = 14）的老年受试者中，使用空腹和胰岛素刺激测量方法评估胰岛素抵抗。CI受试者表现为轻度CI或AD。使用胰岛素抵抗的稳态模型评估（HOMA-IR）测量空腹胰岛素抵抗。使用高胰岛素-正常血糖钳夹评估胰岛素刺激的葡萄糖处置，以计算进入瘦体重（胰岛素刺激的葡萄糖处置的主要部位）的葡萄糖处置率。由于胰岛素可穿过血脑屏障，我们还评估了与基线相比，胰岛素输注是否会改善言语情景记忆。在基础状态和胰岛素刺激状态下，以平衡顺序进行不同但等效版本的认知测试。两组在年龄或体重指数方面无差异。认知受损受试者在空腹时（HOMA-IR；ND：1.09 [1.1] vs. CI：2.01 [2.3]，p = 0.028）和高胰岛素钳夹期间（进入瘦体重的葡萄糖处置率；ND：9.9（4.5）vs. AD 7.2（3.2），p = 0.040）表现出更大的胰岛素抵抗。与ND受试者相比，认知受损受试者的空腹胰岛素也更高（CI：8.7 [7.8] vs. ND：4.2 [3.8] μU/mL；p = 0.023），空腹胰淀素更高（CI：24.1 [39.1] vs. 8.37 [14.2]；p = 0.050），空腹血糖无差异。胰岛素输注对两组的一项言语情景记忆测试（自由和提示选择性回忆测试）产生了有害影响（p < 0.0001），而另一项任务（延迟逻辑记忆）的表现没有变化。在本研究中，尽管与ND对照组相比，认知受损受试者中观察到胰岛素抵抗，但胰岛素输注并未改善记忆。此外，HOMA-IR与葡萄糖处置率之间的显著相关性仅在ND组中存在（p = 0.0002），而在认知受损组中不存在（p = 0.884），这表明这些队列之间可能存在重要的生理差异。
