Association between new markers of cardiovascular risk and hepatic insulin resistance in those at high risk of developing type 2 diabetes

Aim/hypothesis: Hepatic insulin resistance (HIR) is considered to be an independent predictor of metabolic disorders and plays an important role in systemic inflammation, which contributes to abnormalities in cardiovascular disease (CVD) risk factors. The aim of this study was to investigate the relationship between HIR and new markers of cardiovascular risks, including leptin/adiponectin ratio (L/A), lipoprotein(a) [Lp(a)], and tumor necrosis factor alpha (TNF-α), at comparable whole body insulin sensitivity in non-diabetic individuals with or without CVD and at high risk of developing type 2 diabetes. Methods: The HIR index, L/A, Lp(a), and TNF-α were measured in 50 participants with CVD and in 200 without CVD (1:4 ratio). These were also matched for the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda-insulin sensitivity index (ISI) in an observational study design. Results: The HIR index (1.52 ± 0.14 vs. 1.45 ± 0.17, p < 0.02), L/A (3.22 ± 3.10 vs. 2.09 ± 2.27, p < 0.004), and levels of Lp(a) (66.6 ± 49.5 vs. 37.9 ± 3 6.8 mg/dL, p < 0.0001) and TNF-α (18.9 ± 21.8 vs. 5.4 ± 7.1 pg/mL, p < 0.0001) were higher in those with CVD than those without CVD. HOMA-IR and ISI were not significantly different (p = 0.88 and p = 0.35, respectively). The HIR index was directly correlated with L/A (r = 0.41, p < 0.0001), Lp(a) (r = 0.20, p < 0.002), TNF- α (r = 0.14, p < 0.03), and diastolic blood pressure (DBP) (r = 0.13, p < 0.03). The stepwise model analysis showed that L/A, Lp(a), and TNF-α explained about 20% of the variation in the HIR indices of all the participants (p < 0.02). Conclusions/Interpretations: Our results suggest a positive association between HIR and new markers of cardiovascular risk [L/A, Lp(a), and TNF- α] at comparable whole body insulin sensitivity in those with or without CVD and at high risk of developing type 2 diabetes.