Association of Visceral Adipose Tissue and Insulin Resistance with Incident Metabolic Syndrome Independent of Obesity Status: The IRAS Family Study

Abstract

Objective: Although increasing evidence suggests that visceral adipose tissue (VAT) is a major underlying cause of metabolic syndrome (MetS), few studies have measured VAT at multiple time points in diverse populations. VAT and insulin resistance were hypothesized to differ by MetS status within BMI category in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study and, further, that baseline VAT and insulin resistance and increases over time are associated with incident MetS.

Methods: Generalized estimating equations were used for differences in body fat distribution and insulin resistance by MetS status. Mixed effects logistic regression was used for the association of baseline and change in adiposity and insulin resistance with incident MetS across 5 years, adjusted for age, sex, race/ethnicity, and family correlation.

Results: VAT and insulin sensitivity differed significantly by MetS status and BMI category at baseline. VAT and homeostatic model assessment of insulin resistance (HOMA-IR) at baseline (VAT odds ratio [OR] = 1.16 [95% CI: 1.12-2.31]; HOMA-IR OR = 1.85 [95% CI: 1.32-2.58]) and increases over time (VAT OR = 1.55 [95% CI: 1.22-1.98]; HOMA-IR OR = 3.23 [95% CI: 2.20-4.73]) were associated with incident MetS independent of BMI category.

Conclusions: Differing levels of VAT may be driving metabolic heterogeneity within BMI categories. Both overall and abdominal obesity (VAT) may play a role in the development of MetS. Increased VAT over time contributed additional risk.

Figure 1.

Body fat distribution (means and 95% confidence intervals [CI]) by metabolic syndrome status and BMI category adjusted for age, sex, and race/ethnicity in 1,475 participants of the IRAS Family Study at baseline. All estimates derived from a generalized estimating equation using a sandwich estimator for variance to account for the correlation between family members. Open circles = metabolically healthy group. Black circles = group with metabolic syndrome. All estimates are significantly different at the P < 0.05 statistical level, except the following: For visceral adipose tissue: MetS normal weight/healthy overweight, MetS normal weight/MetS overweight, and MetS overweight/healthy obesity. For subcutaneous adipose tissue: healthy overweight/MetS overweight and healthy obesity/MetS obesity.

Figure 2.. Odds ratios and 95% confidence intervals for incident metabolic syndrome at 5 years by visceral adipose tissue (VAT) at baseline and change over time, baseline body mass index (BMI), and HOMA-IR at baseline and change over time in 938 IRAS Family Study participants.

* Mutual adjustment plus adjustment for age, sex, race/ethnicity, and family correlation structure. Baseline VAT by quartile (Q). Change in VAT: No change (less than a 30cm2 change between Visits 1 and 2), Decrease (participant lost 30cm2 or more between Visits), or Increase (participant gained 30cm2 or more between Visits). BMI at baseline (normal, overweight, and obesity by WHO category). Baseline HOMA-IR by quartile (Q). Change in HOMA-IR: No change (less than a 2.5 change), Decrease of at least 2.5, or Increase of least 2.5 between visits.