Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components

Introduction: Association between insulin resistance (IR) and prevalence of coronary artery calcification (CAC) has been inconsistent after adjustment for metabolic syndrome (MetS). In addition, relation of IR to progression of CAC has remained unclear. Recent basic science studies have reported that IR could promote atherosclerosis not only through the mechanisms that involve systemic factors such as dyslipidemia and hypertension, but also through the effect of perturbed insulin signaling at the cell level. Therefore we assessed the hypothesis that IR is associated with CAC prevalence or progression independently of MetS components in a general population. Methods: We conducted a population-based study in a random sample of men aged 40-79 years living in Kusatsu City, Shiga, Japan, without prior coronary heart disease (Shiga Epidemiological Study of Subclinical Atherosclerosis; SESSA). IR was determined by homeostasis model assessment of IR index (HOMA-IR). We measured CAC at baseline and five years later with noncontrast computed tomography. CAC prevalence was defined as baseline CAC score > 0, and CAC progression as a change > 2.5 between the square root transformed values of baseline and follow-up CAC scores. Multivariate logistic regression was performed to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) in total participants and in those without diabetes. Results: Of 1022 total participants at baseline (mean age, 64 ± 10 years), CAC prevalence was found in 658 (64.4%), and of 804 participants at follow-up (mean follow-up duration, 4.9 ± 1.3 years), CAC progression in 371 (46.1%). Even after adjustment for MetS components in addition to other confounding factors, higher HOMA-IR was independently associated with CAC prevalence (OR, 1.35; 95% CI, 1.11-1.64; P = 0.003) and CAC progression (OR, 1.44; 95% CI, 1.18-1.74; P < 0.001). In participants without diabetes (N = 807 at baseline, N = 638 at follow-up), we observed similar positive associations of HOMA-IR with CAC prevalence (OR, 1.30; 95% CI 1.05-1.61; P = 0.016) and CAC progression (OR 1.31; 95% CI 1.03-1.67; P = 0.025). In contrast, fasting glucose and hemoglobin A1c were not related to CAC prevalence and progression. Conclusion: In conclusion, higher IR was associated with CAC prevalence and progression independently of MetS components in general men and also in those without diabetes. Adding measuring of IR as routine clinical examination may provide additional predictive value beyond traditional risk assessment especially among population without diabetes.

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DOES RELATIONSHIP EXIST BETWEEN METABOLIC SYNDROME AND CORONARY ARTERY CALCIFICATION IN KIDNEY TRANSPLANT RECIPIENTS?

Transplantation Journal ◽

10.1097/00007890-201007272-01305 ◽

2010 ◽

Vol 90 ◽

pp. 680

Author(s):

A. Adamowicz ◽

P. Stróżecki ◽

Z. Serafin ◽

Z. Włodarczyk ◽

J. Manitius ◽

...

Keyword(s):

Metabolic Syndrome ◽

Coronary Artery ◽

Kidney Transplant ◽

Coronary Artery Calcification ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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The impact of non-alcoholic fatty liver disease and metabolic syndrome on the progression of coronary artery calcification

Scientific Reports ◽

10.1038/s41598-018-30465-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Yun Kyung Cho ◽

Yu Mi Kang ◽

Jee Hee Yoo ◽

Jiwoo Lee ◽

Seung Eun Lee ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Coronary Artery ◽

Fatty Liver ◽

Coronary Artery Calcification ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

The Impact ◽

Alcoholic Fatty Liver Disease

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Response: The Relationship of Body Composition and Coronary Artery Calcification in Apparently Healthy Korean Adults (Endocrinol Metab 2013;28:33-40, Jung-Hee Yu et al.)

Endocrinology and Metabolism ◽

10.3803/enm.2013.28.2.155 ◽

2013 ◽

Vol 28 (2) ◽

pp. 155

Author(s):

Jung-Hee Yu ◽

Eun-Jung Rhee

Keyword(s):

Body Composition ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Korean Adults ◽

Relationship Of ◽

The Relationship ◽

Apparently Healthy

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The Relationship of Adiponectin/Leptin Ratio with Homeostasis Model Assessment Insulin Resistance Index and Metabolic Syndrome in Apparently Healthy Korean Male Adults

Korean Diabetes Journal ◽

10.4093/kdj.2010.34.4.237 ◽

2010 ◽

Vol 34 (4) ◽

pp. 237 ◽

Cited By ~ 39

Author(s):

Chan-Hee Jung ◽

Eun-Jung Rhee ◽

Ji-Hoon Choi ◽

Ji-Cheol Bae ◽

Seung-Hyun Yoo ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Resistance Index ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Insulin Resistance Index ◽

Relationship Of ◽

The Relationship ◽

Apparently Healthy

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Insulin resistance independently predicts the progression of coronary artery calcification

American Heart Journal ◽

10.1016/j.ahj.2009.02.006 ◽

2009 ◽

Vol 157 (5) ◽

pp. 939-945 ◽

Cited By ~ 53

Author(s):

Keane K. Lee ◽

Stephen P. Fortmann ◽

Joan M. Fair ◽

Carlos Iribarren ◽

Geoffrey D. Rubin ◽

...

Keyword(s):

Insulin Resistance ◽

Coronary Artery ◽

Coronary Artery Calcification

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Abstract 2755: Insulin Resistance and Coronary Artery Calcification measured by Electron Beam Tomography

Circulation ◽

10.1161/circ.116.suppl_16.ii_611-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Robert Lee ◽

Fereshteh Hajsadeghi ◽

Jessica Ramirez ◽

Behnaz Sarlak ◽

Ambarish gopal ◽

...

Keyword(s):

Insulin Resistance ◽

Electron Beam ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Odds Ratio ◽

Electron Beam Tomography ◽

C Reactive Protein ◽

Lipoprotein A ◽

Reactive Protein ◽

Increased Risk

Background: Elevation in the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) has been suggested as a marker of insulin resistance (IR), conferring an increased risk of atherosclerosis in these patients. The association between TG/HDL-C and coronary artery calcification (CAC) measured by computed tomography has yet to be established. The goal of this study was to examine the relationship between IR, as determined by TG/HDL-C ≥ 3.5, and significant CAC (absolute score ≥ 100). Methods: Fasting lipid levels, homocysteine, C reactive protein and lipoprotein (a) levels of 336 asymptomatic individuals, who also underwent electron beam tomography (EBT), were measured. Results: The mean age of participants was 55 ±10 years. 71.7% were male. 37.4% had hypertension, 52.5% had hypercholesterolemia, 12.4% had diabetes mellitus (DM) and 52.5% had family history of premature CHD. Individuals with IR had higher significant CAC (≥100) than those without IR (70% vs. 27%, P=0.0001). After adjustment for age, gender, hypertension, hypercholesterolemia and DM, multivariate regression analysis demonstrated that individuals with IR had more significant CAC (odds ratio 2.1, 95% CI=1.1–3.9, p=0.01). Further sub-analysis revealed that individuals with IR had significantly higher lipoprotein (a) (Lp(a)) than those without IR (odds ratio 1.31, 95% CI=1.09-.16, p=0.03). No significant differences in C-reactive protein (CRP) and homocysteine were found between the two groups. Conclusion: Insulin resistance, as measured by TG/HDL-C ≥ 3.5, was associated with a significantly higher incidence of accelerated atherosclerosis on EBT (absolute CAC score ≥ 100), independent of age, gender and conventional risk factors. IR was also significantly associated with elevated levels of Lp(a). Further studies regarding the clinical significance of insulin resistance and elevated CAC score, as well as its association with Lp(a), may be warranted.

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Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Scientific Reports ◽

10.1038/s41598-019-51367-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Kenji Nishimura ◽

Taichi Murakami ◽

Toshihiro Sakurai ◽

Masashi Miyoshi ◽

Kiyoe Kurahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Insulin Resistant ◽

Cell Dysfunction ◽

Fractionation Analysis ◽

Abnormal Lipid Metabolism ◽

Hdl Metabolism ◽

Relationship Of

Abstract Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

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