LAUSR

Obesity in nonhuman primates has been known for many years and is a well-established and well-studied characteristic of middle-aged rhesus and cynomolgus monkeys, as it is in humans (1,2). Also well established is the link between obesity/overweight in monkeys and the subsequent development of type 2 diabetes mellitus (T2DM) (3,4). Monkeys and humans with “simple” obesity (obesity without diabetes or significant complications), referred to by Kavanagh et al. (5) in this issue as metabolically healthy obesity, progressively move from this relatively healthy state (“insulin sensitive”) (6) through metabolic syndrome (including dyslipidemia, hypertension, and other associated comorbidities) to insulin-resistant obesity and overt diabetes (complete with all of the complications known to humans, if studied long enough during insulin-treated advanced diabetes) (6). The most important feature to note is that it is a progressive process (7), as shown in Figure 1, and that this process or progression begins to be observed in individuals at varying ages. Thus, the penultimate diagnosis of T2DM in rhesus can be made in some animals as early as age 8 in adult rhesus, and its diagnosis, established during longitudinal careful observation, can show onset as late as age 29 (and perhaps later). This is true even if all subjects have received the same diet and environmental conditions. Thus, we have relied upon “phases” in this progression from normal (phase 1 to severe diabetes [phase 9], as shown in Figure 1). Interestingly, this closely parallels the human disease, which can sometimes be diagnosed as early as the teens and certainly as late as the 80s. Only if humans or monkeys with obesity live out their full life-span with metabolic characterization will it be possible to define “healthy obese.” Until then, it must be considered to be a progressive process and likely “healthy” only transiently.