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Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.
Am J Clin Nutr 2015; 102(2):487-96AJ

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.

Authors+Show Affiliations

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;Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark; and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA christina@ellervik.dk.

Pub Type(s)

Comparative Study
Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26156736

Citation

Bergholdt, Helle K M., et al. "Milk Intake Is Not Associated With Low Risk of Diabetes or Overweight-obesity: a Mendelian Randomization Study in 97,811 Danish Individuals." The American Journal of Clinical Nutrition, vol. 102, no. 2, 2015, pp. 487-96.
Bergholdt HK, Nordestgaard BG, Ellervik C. Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals. Am J Clin Nutr. 2015;102(2):487-96.
Bergholdt, H. K., Nordestgaard, B. G., & Ellervik, C. (2015). Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals. The American Journal of Clinical Nutrition, 102(2), pp. 487-96. doi:10.3945/ajcn.114.105049.
Bergholdt HK, Nordestgaard BG, Ellervik C. Milk Intake Is Not Associated With Low Risk of Diabetes or Overweight-obesity: a Mendelian Randomization Study in 97,811 Danish Individuals. Am J Clin Nutr. 2015;102(2):487-96. PubMed PMID: 26156736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals. AU - Bergholdt,Helle K M, AU - Nordestgaard,Børge G, AU - Ellervik,Christina, Y1 - 2015/07/08/ PY - 2014/12/12/received PY - 2015/06/02/accepted PY - 2015/7/10/entrez PY - 2015/7/15/pubmed PY - 2015/10/20/medline KW - Mendelian randomization KW - body mass index KW - diabetes KW - lactase persistence KW - milk KW - overweight SP - 487 EP - 96 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 102 IS - 2 N2 - 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/26156736/Milk_intake_is_not_associated_with_low_risk_of_diabetes_or_overweight_obesity:_a_Mendelian_randomization_study_in_97811_Danish_individuals_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.114.105049 DB - PRIME DP - Unbound Medicine ER -