Early insulin resistance in normoglycemic low-risk individuals is associated with subclinical atherosclerosis

Figures

• 

  Fig. 1. 3-dimensional vascular ultrasound and computed tomography images exemplifying the study findings. (A) Visual example illustrating imaging findings in a participant with HOMA-IR < 2 (reference group), depicting the absence of subclinical atherosclerosis affecting vascular sites. (B) Visual example illustrating imaging findings in a participant with HOMA-IR ≥ 3 (category with the highest HOMA-IR values), revealing a multiterritorial extent of subclinical atherosclerosis in the carotid and femoral arteries and an elevated coronary artery calcium score. HOMA-IR = homeostatic model assessment of insulin resistance

• 

  Fig. 2. HOMA-IR categories, and association with the multiterritorial extent of subclinical atherosclerosis in different vascular territories. (A) Multiterritorial extent of subclinical atherosclerosis (SA), assessed by 2-dimensional vascular ultrasound and non-contrast coronary computed tomography, stratified by HOMA-IR category. Multiterritorial SA extent for this figure is defined by combining data from both imaging techniques to classify individuals as having no disease (0 vascular sites affected) or having focal (1 site), intermediate (2 to 3 sites), or generalized atherosclerosis (4 to 6 sites). (B–D) Presence of SA in different vascular territories stratified by HOMA-IR category. *Indicates statistically significant differences (p < 0.025) as compared to the lowest HOMA-IR category (HOMA-IR < 2, reference group). HOMA-IR = homeostatic model assessment of insulin resistance

• 

  Fig. 3. HOMA-IR categories and plaque volume measured by 3-dimensional vascular ultrasound (3DVUS). (A) Global plaque volume of subclinical atherosclerosis (no disease vs. volume in tertiles) assessed by 3DVUS and stratified by HOMA-IR category. (B, C) The presence of carotid and femoral plaque was assessed by 3DVUS (plaque volume > 0 mm3) and stratified by the HOMA-IR category. *Indicates statistically significant differences as compared to the lowest HOMA-IR category (HOMA-IR < 2, reference group)

• 

  Fig. 4. HOMA-IR, multiterritorial extent of subclinical atherosclerosis, and global plaque volume, stratified by SCORE2 risk category. (A) Number of participants in each SCORE2 risk category, stratified by HOMA-IR category. (B) Extent of subclinical atherosclerosis stratified by SCORE2 risk category. (C) Global plaque volume (absence of disease or plaque volume in tertiles) stratified by SCORE2 risk category. (D) SCORE2 risk-adjusted odds ratios for the multiterritorial extent of subclinical atherosclerosis stratified by HOMA-IR category. (E) Adjusted odds ratios for global plaque volume (absence of disease or plaque volume in tertiles) stratified by HOMA-IR category and SCORE2 risk category. The multivariable models were adjusted for age, sex, smoking status, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index, family history of CVD, and HbA1c. OR = odds ratio, SCORE2 = systematic coronary risk evaluation score 2, HOMA-IR = homeostatic model assessment of insulin resistance, 2DVUS = 2-dimensional vascular ultrasound, 3DVUS = 3-dimensional vascular ultrasound

• 

  Fig. 5. Central Illustration: Early insulin resistance and subclinical atherosclerosis. This study examined 3,741 individuals with normal HbA1c < 6.0% <42 mmol/mol) and no known cardiovascular disease. Higher homeostatic model assessment of insulin resistance (HOMA-IR) values were associated with higher subclinical atherosclerosis (SA) burden as measured by extensive imaging after adjusting for traditional CVRFs and HbA1c. The HOMA-IR index offers a simple and cost-effective way to detect the onset of insulin resistance and SA and could be used to support the implementation of early prevention strategies in clinical practice. 2DVUS, 2-dimensional vascular ultrasound; 3DVUS, 3-dimensional vascular ultrasound; CACS, coronary artery calcium score; IGT, impaired glucose tolerance; IFG, impaired fasting glucose