Abstract
BackgroundCompared to body mass index (BMI), waist circumference (WC), and adiposity measurements, adipose tissue morpho-functionality evaluations are more consistent predictors of cardiometabolic abnormalities. However, these evaluations require determination of adipokines and other non-routine biochemical parameters, which is not feasible in clinical practice. The present study establishes dysfunctional adiposity index (DAI) as a simple, accessible, and reliable marker of early adipocytes morpho-functional abnormalities and cardiometabolic diseases.MethodsTo establish the DAI constant parameters, 340 subjects (134 males and 206 females) without cardiovascular risk factors were selected from a cross-sectional study. Then, DAI was calculated in 36 healthy subjects who underwent subcutaneous adipose tissue biopsy, for whom adipocytes number and size, body composition, circulating adipokines, glucose, insulin, and lipids were also determined. The correlation of DAI with adipocyte morphology (size/number of adipocytes) and functionality (adiponectin/leptin ratio) was analyzed. The receiver operating characteristic curve was used to define the optimal DAI cut-off point to identify metabolic abnormalities. Finally, the independent association of DAI with cardiometabolic abnormalities was determined in 1418 subjects from the cross-sectional study through multivariate analyses.ResultsThe constant parameters to calculate the DAI were [WC/[22.79+[2.68*BMI]]]*[triglycerides (TG, mmol/L)/1.37]*[1.19/high density lipoprotein-cholesterol (HDL-C, mmol/L)] for males, and [WC/[24.02+[2.37*BMI]]]*[TG(mmol/L)/1.32]*[1.43/HDL-C(mmol/L)] for females. In subjects underwent biopsy, DAI correlated with adipocytes mean area (r=0.358; p=0.032), adipocyte number (r=-0.381; p=0.024), adiponectin/leptin ratio (r=-0.483; p=0.003), and systemic inflammation markers. Compared to BMI, WC, and visceral fat, DAI was the only determination associated with insulin resistance (area under the curve: 0.743; p = 0.017). In the cross-sectional study, DAI ≥1.065 was independently associated with diabetes (OR: 1.96; 95%CI: 1.36-2.84), non-alcoholic fatty liver disease (OR: 2.57; 95%CI: 1.98-3.33), subclinical atherosclerosis (OR: 1.74; 95%CI: 1.02-2.94), and hypertension (OR: 1.44; 95%CI: 1.10-1.88).ConclusionsThe present study establishes the constant parameters to calculate the DAI and highlights that a DAI ≥ 1.065 is associated with early cardiometabolic abnormalities independently of adiposity and other risk factors. Since DAI is calculated using accessible parameters routinely used in the clinic, this indicator can be easily incorporated in clinical practice for the early identification of adipose tissue abnormalities in apparently healthy subjects.
Lower plasma PCSK9 in normocholesterolemic subjects is associated with upregulated adipose tissue surface‐expression of LDLR and CD36 and NLRP3 inflammasome
