Abstract

BackgroundType 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients.MethodsProspective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria.Results307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease.ConclusionLow grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Highlights

  • Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance

  • The aim of the present study is to evaluate the relation between hs-C-reactive protein (CRP) plasma levels and cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients with and without clinical manifest vascular disease

  • hemoglobin A1c (HbA1c), LDL-cholesterol, triglycerides and non-HDL-cholesterol all increased over the tertiles, while the estimated glomerular filtration rate decreased

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Summary

Introduction

Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Most of the observed increased cardiovascular risk is attributed to Insulin resistance is a hallmark in patients with type 2 diabetes leading not just to hyperglycemia and to low-grade inflammation. The inflammatory adipocytokines TNF-α and IL-6 are related to elevated levels of circulating C-reactive protein (CRP) [7,8,9] These changes in the release of adipocytokines, from especially visceral adipose tissue, induces a state of systemic insulin resistance and low-grade inflammation [6]. In patients without diabetes, elevated levels of CRP are related to future insulin resistance and development of type 2 diabetes [10]

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