Department of Clinical Sciences, Lund University, Malmö, Sweden.
University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.
Diabet Med. 2020 Jul;37(7):1157-1166. doi: 10.1111/dme.14267. Epub 2020 Feb 26.
The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population-based setting.
Cross-sectional data were obtained from the Swedish population-based Malmö Diet and Cancer Study Re-examination 2007-2012 comprising 3001 older people (mean age 72 years). Through oral glucose tolerance testing (OGTT), fasting and post-load levels of serum insulin, plasma glucagon, serum glucose-dependent insulinotropic peptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) were measured. Insulin resistance and insulin sensitivity levels were calculated. In 454 participants, advanced glycation end products (AGEs) were estimated through skin autofluorescence. Associations between biomarkers and two cognitive tests, the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) respectively, were explored in multiple regression analyses.
Positive associations following adjustments for known prognostic factors were found between MMSE scores and insulin sensitivity (B = 0.822, P = 0.004), 2-h plasma glucagon (B = 0.596, P = 0.026), 2-h serum GIP (B = 0.581, P = 0.040) and 2-h plasma GLP-1 (B = 0.585, P = 0.038), whereas negative associations were found between MMSE scores and insulin resistance (B = -0.734, P = 0.006), fasting plasma GLP-1 (B = -0.544, P = 0.033) and AGEs (B = -1.459, P = 0.030) were found.
Higher levels of insulin sensitivity, GIP and GLP-1 were associated with better cognitive outcomes, but AGEs were associated with worse outcomes, supporting evidence from preclinical studies. Glucagon was linked to better outcomes, which could possibly reflect neuroprotective properties similar to the related biomarker GLP-1 which has similar intracellular properties. Longitudinal and interventional studies are needed to further evaluate neuromodulating effects of these biomarkers. Abstract presented at the European Association for the Study of Diabetes (EASD) 2019, Barcelona, Spain.
本观察性研究旨在探讨人群中葡萄糖代谢生物标志物的生理水平与认知测试结果之间的关系。
本研究的数据来自于基于人群的瑞典马尔默饮食与癌症研究再调查 2007-2012 年，共纳入 3001 名老年人（平均年龄 72 岁）。通过口服葡萄糖耐量试验（OGTT）检测空腹和负荷后血清胰岛素、血浆胰高血糖素、血清葡萄糖依赖性胰岛素释放肽（GIP）和血浆胰高血糖素样肽-1（GLP-1）水平。计算胰岛素抵抗和胰岛素敏感性水平。在 454 名参与者中，通过皮肤自发荧光估算晚期糖基化终产物（AGEs）。采用多元回归分析探讨生物标志物与两项认知测试（简易精神状态检查量表（MMSE）和 A 快速认知速度测试（AQT））之间的关系。
在调整了已知预后因素后，MMSE 评分与胰岛素敏感性（B=0.822，P=0.004）、2 小时血浆胰高血糖素（B=0.596，P=0.026）、2 小时血清 GIP（B=0.581，P=0.040）和 2 小时血浆 GLP-1（B=0.585，P=0.038）呈正相关，而与胰岛素抵抗（B=-0.734，P=0.006）、空腹血浆 GLP-1（B=-0.544，P=0.033）和 AGEs（B=-1.459，P=0.030）呈负相关。
更高的胰岛素敏感性、GIP 和 GLP-1 水平与更好的认知结果相关，而 AGEs 与更差的结果相关，支持来自临床前研究的证据。胰高血糖素与更好的结果相关，这可能反映了类似 GLP-1 的神经保护特性，GLP-1 具有相似的细胞内特性。需要进行纵向和干预性研究来进一步评估这些生物标志物的神经调节作用。该摘要在西班牙巴塞罗那举行的 2019 年欧洲糖尿病研究协会（EASD）年会上发表。
