Abstract
Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. Methods: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic–euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81–44.06] vs. 30.82 [21.48–38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.
Highlights
Type 2 diabetes mellitus (T2D) is a metabolic disorder that accounts for approximately90% of all diabetic patients [1,2]
A number of preclinical studies have shown that myocardial insulin resistance, which is characterized by inefficient energy metabolism, co-occurs with systemic insulin resistance and contributes to post-ischemic heart failure [4]
The exclusion criteria were: (1) a clinical diagnosis of type 1 diabetes and/or (2) any type of cardiovascular disease (CVD), (3) any absolute or relative contraindication to Positron emission tomography/computed tomography (PET/CT), (4) any concomitant disease associated with a short life expectancy
Summary
Type 2 diabetes mellitus (T2D) is a metabolic disorder that accounts for approximately90% of all diabetic patients [1,2]. Many clinical trials have shown that systemic insulin resistance is an independent risk factor for heart failure and cardiovascular death [1]. Increasing evidence points to insulin resistance as the primary etiologic factor in the development of nonischemic heart failure [2,3]. A number of preclinical studies have shown that myocardial insulin resistance (mIR), which is characterized by inefficient energy metabolism, co-occurs with systemic insulin resistance and contributes to post-ischemic heart failure [4]. Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18 F-FDG uptake and twenty-six a marginal increase, revealing mIS and mIR, respectively.
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