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

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Abstract

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.

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Abbreviations

AUC:

area under the curve

BMI:

body mass index

CVD:

cardiovascular disease

FFM:

free fat mass

FM:

fat mass

HDL:

high density lipoprotein

HIR:

hepatic insulin resistance

HIR index:

hepatic insulin resistance index

HOMA-IR:

homeostasis model assessment of insulin resistance

IR:

insulin resistance

L/A:

leptin/adiponectin ratio

LDL:

low density lipoprotein

Matsuda-ISI::

Matsuda insulin sensitivity index

MS:

metabolic syndrome

OGTT:

oral glucose tolerance test

TNF-α:

tumor necrosis factor alpha

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Author contributions

PMP and LDM designed the study. PMP, LDM, and AM conducted clinical determinations, BF, EG, and SS acquired data, PMP, LDM and CBC performed statistical analysis. PMP, LDM, and CBC wrote the manuscript. PMP, LDM, and EB contributed to the manuscript revision

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This research did not receive any specific grant from funding agencies in the public, commercial, or not for-profit sectors.

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Authors and Affiliations

  1. Cardio-Metabolism and Clinical Trials Unit, Diabetes Research Institute, Department of Internal Medicine, IRCCS San Raffaele Institute, Via Olgettina 60, 20132 Milan, MI, Italy

    Lucilla D. Monti, Camillo Bechi Genzano, Andrea Magistro, Emanuele Bosi & Piermarco Piatti

  2. Cardio-Diabetes and Core Lab Unit, Diabetes Research Institute, Department of Internal Medicine, IRCCS San Raffaele Institute, Via Olgettina 60, 20132 Milan MI, Italy

    Lucilla D. Monti, Barbara Fontana, Elena Galluccio, Serena Spadoni & Emanuele Bosi

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  1. Lucilla D. Monti
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Correspondence to Lucilla D. Monti.

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Monti, L.D., Genzano, C.B., Fontana, B. et al. Association between new markers of cardiovascular risk and hepatic insulin resistance in those at high risk of developing type 2 diabetes. Endocrine 75, 409–417 (2022). https://doi.org/10.1007/s12020-021-02868-x

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