Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, 1 Autumn Street, BCH 3428, Boston, MA, 02115, USA.
Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
Diabetologia. 2020 May;63(5):977-986. doi: 10.1007/s00125-020-05101-y. Epub 2020 Feb 4.
AIMS/HYPOTHESIS: Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.
Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.
Negative phenotypic correlations (ρ) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d']: ρ = -0.143, p = 0.001), verbal memory (California Verbal Learning Test [CVLT] recall: ρ = -0.111, p = 0.004) and face memory (Penn Face Memory Test [PFMT]: ρ = -0.127, p = 0.002; PFMT Delayed: ρ = -0.148, p = 2 × 10), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (ρ) were also observed between type 2 diabetes and measures of attention (CPT d': ρ = -0.401, p = 0.001), working memory (digit span backward test: ρ = -0.380, p = 0.005), and face memory (PFMT: ρ = -0.476, p = 2 × 10; PFMT Delayed: ρ = -0.376, p = 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d': β = -0.219, p = 0.005), working memory (digit span backward: β = -0.326, p = 0.035), and face memory (PFMT: β = -0.171, p = 0.023; PFMT Delayed: β = -0.215, p = 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level.
CONCLUSIONS/INTERPRETATION: These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease.
The data analysed in this study is available in dbGaP: www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2.
目的/假设：2 型糖尿病与认知障碍有关，但尚不清楚常见的遗传因素是否会同时影响 2 型糖尿病的风险和认知能力。
使用来自扩展家系的 1892 名墨西哥裔美国人的数据（包括 402 名 2 型糖尿病患者），我们使用全面的神经心理学测试组合来检查 2 型糖尿病与认知功能之间是否存在潜在的多效性。
观察到 2 型糖尿病与注意力（连续性能测试 [CPT d']：ρ=−0.143，p=0.001）、语言记忆（加利福尼亚语言学习测试 [CVLT] 回忆：ρ=−0.111，p=0.004）和面孔记忆（宾夕法尼亚面孔记忆测试 [PFMT]：ρ=−0.127，p=0.002；PFMT 延迟：ρ=−0.148，p=2×10）之间存在负表型相关性，复制了 2 型糖尿病认知障碍的发现。也观察到 2 型糖尿病与注意力（CPT d'：ρ=−0.401，p=0.001）、工作记忆（数字跨度回溯测试：ρ=−0.380，p=0.005）和面孔记忆（PFMT：ρ=−0.476，p=2×10；PFMT 延迟：ρ=−0.376，p=0.005）之间存在负遗传相关性，这表明导致 2 型糖尿病的相同遗传因素也会影响这些领域的认知表现不佳。使用表型评分值方法，这些领域的表现也与 2 型糖尿病风险相关。具体来说，在注意力测量（CPT d'：β=−0.219，p=0.005）、工作记忆（数字跨度回溯：β=−0.326，p=0.035）和面孔记忆（PFMT：β=−0.171，p=0.023；PFMT 延迟：β=−0.215，p=0.005）方面，2 型糖尿病患者的表现最差，而未受影响/无关个体的表现最好，而与 2 型糖尿病患者相关的个体的表现处于中间水平。
结论/解释：这些发现表明，认知障碍可能是 2 型糖尿病的一个有用的表型，因此有助于阐明这种慢性疾病的病理生理基础。
本研究分析的数据可在 dbGaP 中获得：www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2。
