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Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the 'common soil' hypothesis.

ABSTRACT: BACKGROUND:Chronic low-grade inflammation and associated insulin resistance and metabolic abnormalities have been proposed as 'common soil' for diabetes mellitus (DM) and cardiovascular disease (CVD). This paper aimed to investigate the inflammatory profiles of DM and CVD and to distinguish their shared and specific markers. METHODS:Based on the Malmö Diet and Cancer cohort, total and differential leukocyte counts were measured in 25,969 participants without previous DM or CVD and were studied in relation to incident DM (mean follow-up 17.4?±?5.58 years) and incident CVD (i.e., coronary events, including fatal and nonfatal myocardial infarction, or stroke); mean follow-up 17.7?±?5.46 years, using multivariable Cox regression models. Furthermore, plasma concentrations of another seven inflammatory markers were examined in relation to incident DM and incident CVD in a sub-cohort of 4658 participants. The associations of each inflammatory marker with incident DM versus incident CVD were compared using the Lunn-McNeil competing risks approach. In sensitivity analyses, those who developed both DM and CVD during follow-up were excluded. RESULTS:After adjustment for conventional risk factors, total and differential leukocyte counts, orosomucoid, and C-reactive protein were associated with an increased risk of both DM and CVD. Neutrophil to lymphocyte ratio, ceruloplasmin, alpha1-antitrypsin and soluble urokinase plasminogen activator receptor predicted increased risk of CVD but not DM, while haptoglobin and complement C3 showed the opposite pattern. In competing risks analyses, lymphocyte count and complement C3 had stronger associations with risk of DM than with risk of CVD (p for equal associations?=?0.020 and 0.006). The reverse was true for neutrophil to lymphocyte ratio (p for equal associations?=?0.025). Results were consistent in sensitivity analyses. CONCLUSIONS:The results indicated substantial similarities in the inflammatory profiles associated with DM and CVD. However, there are also significant differences. These findings may help discriminate between individuals at elevated risk of DM and those at elevated risk of CVD, which is a prerequisite for targeted therapies.

SUBMITTER: Bao X

PROVIDER: S-EPMC5996509 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the 'common soil' hypothesis.

Bao Xue X Bao Xue X Borné Yan Y Johnson Linda L Muhammad Iram Faqir IF Persson Margaretha M Niu Kaijun K Engström Gunnar G

Cardiovascular diabetology 20180612 1

<h4>Background</h4>Chronic low-grade inflammation and associated insulin resistance and metabolic abnormalities have been proposed as 'common soil' for diabetes mellitus (DM) and cardiovascular disease (CVD). This paper aimed to investigate the inflammatory profiles of DM and CVD and to distinguish their shared and specific markers.<h4>Methods</h4>Based on the Malmö Diet and Cancer cohort, total and differential leukocyte counts were measured in 25,969 participants without previous DM or CVD and ...[more]

PMID: 29895294

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Project description:BackgroundIn observational and experimental studies, allergic diseases (AD) have been reported to be associated with some types of cardiovascular diseases (CVD), as both share common pathophysiological processes involving inflammation and metabolic disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between AD and CVD.MethodsWe utilized publicly available genome-wide association study (GWAS) summary statistics data from European participants in the UK Biobank and the IEU Open GWAS database. Genetic variants associated with AD, asthma, and CVD were identified and used as instrumental variables to investigate the genetically causal association between them. MR analyses were performed using various analytical methods, including inverse variance weighted-fixed effects (IVW-FE), inverse variance weighted-multiplicative random effects (IVW-RE), MR-Egger, weighted median, weighted mode, and maximum likelihood. Sensitivity tests were conducted to assess the validity of the causality.ResultsThe MR analysis with the IVW method revealed a genetically predicted association between AD and essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], as well as between asthma and atrial fibrillation (OR=1.001, 95% CI: 1.0004-1.0017, P=6.43E-05). In the reverse MR analyses, heart failure was associated with allergic diseases (OR=0.0045, 95% CI: 1.1890E-04 - 0.1695, P=0.004), while atherosclerosis (OR=8.7371E-08, 95% CI: 1.8794E-14 - 4.0617E-01, P=0.038) and aortic aneurysm and dissection (OR=1.7367E-07, 95% CI: 3.8390E-14 - 7.8567E-01, P=0.046) might be protective factors of asthma. However, after a Bonferroni correction, only the association between asthma and atrial fibrillation remained robust.ConclusionThe MR study revealed that asthma is a predominant risk of atrial fibrillation in European individuals, consistent with most experimental and observational studies. Whether AD affects other CVD and the causality between them needs further investigation.

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Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the 'common soil' hypothesis.

Publications

Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the 'common soil' hypothesis.

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