Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes

Abstract

Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.

Leptin is associated with cardiopulmonary fitness independent of body-mass index and insulin sensitivity in adolescents with type 1 diabetes: a brief report from the EMERALD study

“…Huby et al demonstrated that leptin contributes to CVD by upregulating aldosterone synthesis leading to increased blood pressures, and by promoting endothelial dysfunction and the expression of profibrotic markers in the heart (16). Other possible mechanisms include adiposopathy (17) and leptin related mitochondrial dysfunction (18), but these pathways have to our knowledge not been examined in T1D.…”

Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk

“…Moreover, the adiponectin/leptin ratio may constitute also a biomarker of insulin resistance during pregnancy [27] and of the presence of metabolic derangements in polycystic ovary syndrome [28]. Importantly, a recent study has shown that besides fitness and waist circumference the only other variable with an important independent contribution to predict insulin sensitivity in multiple regression models was adipose tissue dysfunction as reflected by the adiponectin/leptin ratio [29].…”

Abdominal obesity and metabolic syndrome: exercise as medicine?

“…Insulin resistance is thought to be the common denominator in the development of metabolic syndrome. In addition, evidence suggests that systemic inflammation is an important factor in its development, through the development of insulin resistance [ 18 – 21 ]. Visceral fat deposits (abdominal adiposity) are associated with the development of adipose cells that are enlarged and dysfunctional (adiposopathy, or ‘sick fat’) [ 21 ].…”

“…In addition, evidence suggests that systemic inflammation is an important factor in its development, through the development of insulin resistance [ 18 – 21 ]. Visceral fat deposits (abdominal adiposity) are associated with the development of adipose cells that are enlarged and dysfunctional (adiposopathy, or ‘sick fat’) [ 21 ]. Dysfunctional adipose tissue secretes pro-inflammatory biomarkers including prostaglandins, C-reactive protein (CRP), and cytokines such as interleukins (e.g.…”