Submitted to: Journal of Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/21/2012
Publication Date: 1/23/2013
Citation: Hruby, A., Jacques, P.F., Meigs, J.B., Mckeown, N.M., Nettleton, J.A. 2013. Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 charge consortium studies. Journal of Nutrition. 142(10):1859-1864. Interpretive Summary: Magnesium is a nutrient that is found in many foods and beverages, including leafy greens, whole grains, coffee, and chocolate. However, despite its wide availability in food, many people do not meet their daily magnesium intake recommendations. Low magnesium intake has been linked to a wide variety of disease conditions, including type 2 diabetes. Some studies have shown that higher magnesium intake in people with type 2 diabetes helps improve some of the markers of their disease status. In this study, the authors wanted to investigate whether magnesium intake is related to blood glucose and insulin, in people free of diabetes. They also wanted to find out if certain genetic characteristics that affect the body’s handling of blood glucose, insulin, and magnesium help determine the way dietary magnesium is used by the body to alter blood glucose and insulin. The analysis was cross-sectional, meaning the authors looked at people at one time point. Like many studies involving genetics, the authors needed a lot of data, so they pooled together data from 15 studies across the United States and Europe, gathering relevant information on over 50,000 people. These people were all of European descent (Caucasian) and ranged in age from about 11 years old into their 80s. The researchers found that higher magnesium intake was indeed associated with slightly lower blood glucose and insulin. They found some hints — but no definitive conclusions — about how genetics interacts with dietary magnesium, and the genetic questions still merit further research. In conclusion, higher magnesium intake — easily accomplished by consuming more readily-available magnesium-rich foods — is associated with lower blood glucose and insulin in Caucasians free of diabetes.
Technical Abstract: Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism impact the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effect meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L), and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, body mass index, and behavioral risk factors, magnesium (per 50 mg/d increment) was inversely associated with fasting glucose [beta (95% CI): 0.009 mmol/L ( 0.013, 0.005), P<0.0001] and insulin [ 0.020 ln pmol/L ( 0.024, 0.017), P<0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached statistical significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed nominal association (uncorrected P=0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed nominal interaction (uncorrected, both P=0.02) with magnesium on glucose. Consistent with other studies, higher magnesium intake associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence, and magnesium interaction with select loci, suggest further investigation is warranted.