人群中血糖水平对微血管和大血管疾病的影响：一项孟德尔随机化研究。
Impact of Glucose Level on Micro- and Macrovascular Disease in the General Population: A Mendelian Randomization Study.
机构信息
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
出版信息
Diabetes Care. 2020 Apr;43(4):894-902. doi: 10.2337/dc19-1850. Epub 2020 Feb 13.
OBJECTIVE
To evaluate whether high glucose levels in the normoglycemic range and higher have a causal genetic effect on risk of retinopathy, neuropathy, nephropathy, chronic kidney disease (CKD), peripheral arterial disease (PAD), and myocardial infarction (MI; positive control) in the general population.
RESEARCH DESIGN AND METHODS
This study applied observational and one-sample Mendelian randomization (MR) analyses to individual-level data from 117,193 Danish individuals, and validation by two-sample MR analyses on summary-level data from 133,010 individuals from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), 117,165 from the CKDGen Consortium, and 452,264 from the UK Biobank.
RESULTS
Observationally, glucose levels in the normoglycemic range and higher were associated with high risks of retinopathy, neuropathy, diabetic nephropathy, PAD, and MI (all for trend <0.001). In genetic causal analyses, the risk ratio for a 1 mmol/L higher glucose level was 2.01 (95% CI 1.18-3.41) for retinopathy, 2.15 (1.38-3.35) for neuropathy, 1.58 (1.04-2.40) for diabetic nephropathy, 0.97 (0.84-1.12) for estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m, 1.19 (0.90-1.58) for PAD, and 1.49 (1.02-2.17) for MI. Summary-level data from the MAGIC, the CKDGen Consortium, and the UK Biobank gave a genetic risk ratio of 4.55 (95% CI 2.26-9.15) for retinopathy, 1.48 (0.83-2.66) for peripheral neuropathy, 0.98 (0.94-1.01) for eGFR <60 mL/min/1.73 m, and 1.23 (0.57-2.67) for PAD per 1 mmol/L higher glucose level.
CONCLUSIONS
Glucose levels in the normoglycemic range and higher were prospectively associated with a high risk of retinopathy, neuropathy, diabetic nephropathy, eGFR <60 mL/min/1.73 m, PAD, and MI. These associations were confirmed in genetic causal analyses for retinopathy, neuropathy, diabetic nephropathy, and MI, but they could not be confirmed for PAD and seemed to be refuted for eGFR <60 mL/min/1.73 m.
目的
评估正常血糖范围内的高血糖水平以及更高的血糖水平是否对一般人群的视网膜病变、神经病变、糖尿病肾病、慢性肾脏病 (CKD)、外周动脉疾病 (PAD) 和心肌梗死 (MI; 阳性对照) 风险具有因果遗传效应。
研究设计和方法
本研究应用观察性和单样本孟德尔随机化 (MR) 分析对来自 117,193 名丹麦个体的个体水平数据进行了分析，并通过对来自 Meta-Analyses of Glucose and Insulin-Related Traits 协作组 (MAGIC) 的 133,010 名个体、CKDGen 协作组的 117,165 名个体和 UK Biobank 的 452,264 名个体的汇总水平数据进行两样本 MR 分析进行了验证。
结果
观察性研究表明，正常血糖范围内和更高的血糖水平与视网膜病变、神经病变、糖尿病肾病、PAD 和 MI 的高风险相关（所有趋势 P<0.001）。在遗传因果分析中，血糖水平每升高 1 mmol/L，视网膜病变的风险比为 2.01（95%CI 1.18-3.41），神经病变为 2.15（1.38-3.35），糖尿病肾病为 1.58（1.04-2.40），肾小球滤过率（eGFR）<60 mL/min/1.73 m 为 0.97（0.84-1.12），PAD 为 1.19（0.90-1.58），MI 为 1.49（1.02-2.17）。来自 MAGIC、CKDGen 协作组和 UK Biobank 的汇总水平数据得出的遗传风险比为 4.55（95%CI 2.26-9.15），用于视网膜病变，1.48（83-2.66）用于周围神经病变，0.98（94-1.01）用于 eGFR <60 mL/min/1.73 m，以及 1.23（57-2.67）用于 PAD，血糖水平每升高 1 mmol/L。
结论
正常血糖范围内和更高的血糖水平与视网膜病变、神经病变、糖尿病肾病、eGFR <60 mL/min/1.73 m、PAD 和 MI 的高风险相关。这些关联在视网膜病变、神经病变、糖尿病肾病和 MI 的遗传因果分析中得到了证实，但在 PAD 中无法得到证实，并且似乎对 eGFR <60 mL/min/1.73 m 进行了反驳。
Zotero 插件