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.
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 affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects 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, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.
Tufts University Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Adela
A
Hruby
Julius S
JS
Ngwa
Frida
F
Renström
Mary K
MK
Wojczynski
Andrea
A
Ganna
Göran
G
Hallmans
Denise K
DK
Houston
Paul F
PF
Jacques
Stavroula
S
Kanoni
Terho
T
Lehtimäki
Rozenn N
RN
Lemaitre
Ani
A
Manichaikul
Kari E
KE
North
Ioanna
I
Ntalla
Emily
E
Sonestedt
Toshiko
T
Tanaka
Frank J A
FJ
van Rooij
Stefania
S
Bandinelli
Luc
L
Djoussé
Efi
E
Grigoriou
Ingegerd
I
Johansson
Kurt K
KK
Lohman
James S
JS
Pankow
Olli T
OT
Raitakari
Ulf
U
Riserus
Mary
M
Yannakoulia
M Carola
MC
Zillikens
Neelam
N
Hassanali
Yongmei
Y
Liu
Dariush
D
Mozaffarian
Constantina
C
Papoutsakis
Ann-Christine
AC
Syvänen
André G
AG
Uitterlinden
Jorma
J
Viikari
Christopher J
CJ
Groves
Albert
A
Hofman
Lars
L
Lind
Mark I
MI
McCarthy
Vera
V
Mikkilä
Kenneth
K
Mukamal
Oscar H
OH
Franco
Ingrid B
IB
Borecki
L Adrienne
LA
Cupples
George V
GV
Dedoussis
Luigi
L
Ferrucci
Frank B
FB
Hu
Erik
E
Ingelsson
Mika
M
Kähönen
W H Linda
WH
Kao
Stephen B
SB
Kritchevsky
Marju
M
Orho-Melander
Inga
I
Prokopenko
Jerome I
JI
Rotter
David S
DS
Siscovick
Jacqueline C M
JC
Witteman
Paul W
PW
Franks
James B
JB
Meigs
Nicola M
NM
McKeown
Jennifer A
JA
Nettleton
D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000235:genetics; D008274:Magnesium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050053:TRPM Cation Channels / Q000235:genetics; D014131:Trace Elements / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D014131:Trace Elements; D008274:Magnesium