牛奶摄入量与糖尿病或超重肥胖的低风险无关：一项对97811名丹麦人的孟德尔随机化研究。

Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

作者信息

Bergholdt Helle K M, Nordestgaard Børge G, Ellervik Christina

机构信息

Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark;

出版信息

Am J Clin Nutr. 2015 Aug;102(2):487-96. doi: 10.3945/ajcn.114.105049. Epub 2015 Jul 8.

DOI:10.3945/ajcn.114.105049

PMID:26156736

Abstract

BACKGROUND

High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown.

OBJECTIVE

We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically.

DESIGN

In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence.

RESULTS

Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally.

CONCLUSIONS

High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification bias.

摘要

背景

观察性研究表明，高乳制品/牛奶摄入量与2型糖尿病风险较低相关，但这是否代表因果关系尚不清楚。

目的

我们通过观察性研究和基因研究检验了高牛奶摄入量与2型糖尿病及超重肥胖风险较低相关的假设。

设计

在来自丹麦普通人群的97,811名个体中，我们通过观察性研究以及乳糖酶（LCT）基因上游的LCT-13910 C/T基因型[多态性（rs4988235）]来研究2型糖尿病和超重肥胖的发病风险，其中TT和TC基因型与乳糖酶持续性相关，CC基因型与非持续性相关。

结果

观察性研究中，与不摄入牛奶相比，摄入任何量牛奶者患2型糖尿病的风险比（HR）为1.10（95%置信区间：0.98, 1.24；P = 0.11），而超重肥胖的比值比（OR）为1.06（1.02, 1.09；P = 0.002）。乳糖酶TT/TC持续性个体的牛奶摄入量中位数为5杯/周（四分位间距：0 - 10），CC非持续性个体为3杯/周（0 - 7）。基因研究中，与CC非持续性相比，乳糖酶TT/TC持续性个体患2型糖尿病的OR为0.96（0.86, 1.08；P = 0.50），超重肥胖的OR为1.06（1.00, 1.12；P = 0.04）。在2型糖尿病的分层分析中，摄入牛奶和未摄入牛奶者的相应值分别为0.88（0.76, 1.03；P = 0.11）和1.35（1.07, 1.70；P = 0.01）（P交互作用：0.002），而未发现超重肥胖存在基因 - 牛奶交互作用。对于每周多摄入1杯牛奶，2型糖尿病的基因风险比为0.99（0.93, 1.06），相应的观察性风险为1.01（1.00, 1.01）。对于超重肥胖，基因研究和观察性研究的相应值分别为1.01（1.00, 1.02）和1.00（1.00, 1.01）。