Concept of ectopic fat as a cause of tissue insulin resistance
It appears that individuals prone to T2DM (based in part on their nonmodifiable characteristics) show a greater propensity to accumulate visceral or ectopic fat for a given weight. Interestingly this characteristic, in turn, may be a downstream consequence of “impaired” subcutaneous fat storage capacity, the mechanisms of which deserve further research. As an extreme example of this concept, lipodystrophic individuals have an impaired ability to store subcutaneous fat and, as a consequence, they accumulate fat in visceral and ectopic tissues and so have marked insulin resistance . It is also apparent that certain ethnic groups at heightened diabetes risk may have a tendency to store fat centrally sooner (i.e., at lower average BMI) than European whites and consequently develop diabetes at lower average BMI values and around a decade earlier . At the other extreme, there are many individuals, particularly women, who despite attaining very high BMIs, even as high as 50 to 60 kg m−2, remain insulin sensitive and normolipemic. Imaging studies have shown these individuals to have low levels of visceral and ectopic fat but a high subcutaneous fat content . In other words, the location of fat storage (subcutaneous vs. visceral/ectopic) appears critical as to the BMI and time that an individual develops metabolic complications linked to insulin resistance. Figure 23.2 summarizes the concept of ectopic fat and its importance to insulin resistance.