Identification and characterization of metabolically benign obesity in humans

Background: Obesity represents a risk factor for insulin resistance, type 2 diabetes mellitus, and atherosclerosis. In addition, for any given amount of total body fat, an excess of visceral fat or fat accumulation in the liver and skeletal muscle augments the risk. Conversely, even in obesity, a metabolically benign fat distribution phenotype may exist. Methods: In 314 subjects, we measured total body, visceral, and subcutaneous fat with magnetic resonance (MR) tomography and fat in the liver and skeletal muscle with proton MR spectroscopy. Insulin sensitivity was estimated from oral glucose tolerance test results. Subjects were divided into 4 groups: normal weight (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared], <25.0), overweight (BMI, 25.0-29.9), obese-insulin sensitive (IS) (BMI, >= 30.0 and placement in the upper quartile of insulin sensitivity), and obese-insulin resistant (IR) (BMI, >= 30.0 and placement in the lower 3 quartiles of insulin sensitivity). Results: Total body and visceral fat were higher in the overweight and obese groups compared with the normal-weight group (P <.05); however, no differences were observed between the obese groups. In contrast, ectopic fat in skeletal muscle (P <.001) and particularly the liver (4.3%+/- 0.6% vs 9.5%+/- 0.8%) and the intima-media thickness of the common carotid artery (0.54 +/- 0.02 vs 0.59 +/- 0.01 mm) were lower and insulin sensitivity was higher (17.4 +/- 0.9 vs 7.3 +/- 0.3 arbitrary units) in the obese-IS vs the obese-IR group (P <.05). Unexpectedly, the obese-IS group had almost identical insulin sensitivity and the intima-media thickness was not statistically different compared with the normal-weight group (18.2 +/- 0.9 AU and 0.51 +/- 0.02 mm, respectively). Conclusions: A metabolically benign obesity that is not accompanied by insulin resistance and early atherosclerosis exists in humans. Furthermore, ectopic fat in the liver may be more important than visceral fat in the determination of such a beneficial phenotype in obesity.