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.
Gkrania-Klotsas
Effrossyni
E
MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
Ye
Zheng
Z
Cooper
Andrew J
AJ
Sharp
Stephen J
SJ
Luben
Robert
R
Biggs
Mary L
ML
Chen
Liang-Kung
LK
Gokulakrishnan
Kuppan
K
Hanefeld
Markolf
M
Ingelsson
Erik
E
Lai
Wen-An
WA
Lin
Shih-Yi
SY
Lind
Lars
L
Lohsoonthorn
Vitool
V
Mohan
Viswanathan
V
Muscari
Antonio
A
Nilsson
Goran
G
Ohrvik
John
J
Chao Qiang
Jiang
J
Jenny
Nancy Swords
NS
Tamakoshi
Koji
K
Temelkova-Kurktschiev
Theodora
T
Wang
Ya-Yu
YY
Yajnik
Chittaranjan Sakerlal
CS
Zoli
Marco
M
Khaw
Kay-Tee
KT
Forouhi
Nita G
NG
Wareham
Nicholas J
NJ
Langenberg
Claudia
C
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