Differential white blood cell count and type 2 diabetes: systematic review and meta-analysis of cross-sectional and prospective studies.
OBJECTIVE
Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.


METHODS
Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.


RESULTS
The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I(2) = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.


CONCLUSIONS
A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.
MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
Effrossyni
E
Gkrania-Klotsas
Zheng
Z
Ye
Andrew J
AJ
Cooper
Stephen J
SJ
Sharp
Robert
R
Luben
Mary L
ML
Biggs
Liang-Kung
LK
Chen
Kuppan
K
Gokulakrishnan
Markolf
M
Hanefeld
Erik
E
Ingelsson
Wen-An
WA
Lai
Shih-Yi
SY
Lin
Lars
L
Lind
Vitool
V
Lohsoonthorn
Viswanathan
V
Mohan
Antonio
A
Muscari
Goran
G
Nilsson
John
J
Ohrvik
Jiang
J
Chao Qiang
Nancy Swords
NS
Jenny
Koji
K
Tamakoshi
Theodora
T
Temelkova-Kurktschiev
Ya-Yu
YY
Wang
Chittaranjan Sakerlal
CS
Yajnik
Marco
M
Zoli
Kay-Tee
KT
Khaw
Nita G
NG
Forouhi
Nicholas J
NJ
Wareham
Claudia
C
Langenberg
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies