Helicobacter pylori cytotoxin-associated gene-A antibodies do not predict complications or death in type 2 diabetes: the Fremantle Diabetes Study.
OBJECTIVE
There is cross-sectional evidence that CagA antigen produced by Helicobacter pylori is associated with coronary heart disease, stroke, atrial fibrillation (AF) and microalbuminuria, but no large-scale longitudinal studies have been conducted in diabetic patients. We aimed to determine whether cytotoxin-associated gene-A (CagA) seropositivity is independently associated with important vascular outcomes in type 2 diabetes.


METHODS
We studied 1179 type 2 patients from a well characterized community-based cohort who had available sera from baseline assessment between 1993 and 1996, and follow-up for incident events to end-June 2007. H. pylori IgG and CagA antibodies at baseline were measured by validated ELISA. Multiple logistic/linear regression analysis and Cox proportional hazards modelling were used to determine independent baseline associates of prevalent and incident complications, respectively, including H. pylori/CagA serostatus.


RESULTS
At baseline, 62.0% of patients were H. pylori seropositive and 37.7% were both H. pylori and CagA seropositive. CagA seropositivity was not independently associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CVD), peripheral arterial disease or AF at baseline (P > 0.41), but there was a significant inverse association with ln(urinary albumin:creatinine) (P = 0.033). There were no independent associations between CagA seropositivity and incident CHD/CVD or progression to microalbuminuria (P > 0.20). During follow-up, 480 patients (40.7%) died, 246 (50.2%) from cardiovascular causes. After adjustment for other variables,CagA seropositivity was weakly protective against cardiovascular death (P = 0.024).


CONCLUSIONS
CagA seropositivity is not a risk factor for chronic vascular complications of type 2 diabetes. Assay of CagA antibodies does not contribute significantly to clinical management outside gastroenterological indications.
Schimke
Katrin
K
School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
Chubb
Stephen A P
SA
Davis
Wendy A
WA
Davis
Timothy M E
TM
D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001315:Australia; D001426:Bacterial Proteins / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D002423:Cause of Death; D048909:Diabetes Complications / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology* / Q000401:mortality; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori