Obesity is a significant risk factor for the development of a number of diseases, but the first that comes to mind is type 2 diabetes. 

Type 2 diabetics have a greater risk of developing—and dying—from nephropathy, micro- and macrovascular disease, impaired wound healing and neuropathy.  So invoking the transitive property, obesity should be associated with increased mortality and shorter life span.  Yet a surprising number of studies have shown that patients with a type 2 diabetes (and other diseases), live longer than their normal weight counterparts—the  so-called obesity paradox. 

To me, this just doesn’t make a lot of sense, so why do the data suggest otherwise?  A recent study published in the New England Journal of Medicine offers some insights  that suggest the previous observations, at least for patients with type 2 diabetes,  might be flawed for including small study populations and omitting the effects of smoking and undiagnosed illnesses that  contribute to weight loss and decreased longevity. (In other words, when you fail to consider the contribution of smoking and other co-morbid conditions—that might result in a thinner body type—to overall mortality it can, statistically speaking, weaken the link between obesity and premature death.)

 In fact, the data reported by the authors of the NEJM study (which included something like 11,000 patients ) suggested that increased all-cause mortality risk was greatest for those at both ends of the BMI curve.  Does it appear that there is a paradox within the paradox?

Perhaps, the issues lie in how we ask the question and whether or not we’re even asking the right questions with respect to type 2 diabetes!  For instance, we define obesity and being overweight according to body mass index (BMI) cut-offs based on a distribution across the population.  And while those cut-offs have implications for treatment and classifications (and all those diet plans, I suppose) BMI tends to be normally distributed across the population.  That makes absolute classification a bit fuzzy. 

BMI is an easily calculated parameter.  Estimate a patient’s mass in kg and divide it by her/his height in m2. But it doesn’t measure adiposity (fat deposition) per se, or, more importantly where that adipose tissue is located.  It might hold that as diabetic, insulin resistant patients improve their sensitivity to the hormone they also develop more muscle mass (which is quite a bit denser than adipose), and increase BMI without significantly altering overall adiposity.

 To that point, fitness may have been an overlooked factor.  The authors of the NEJM study indicated that fitness didn’t make a difference in their results, so they didn’t include them.  It’s hard to make a judgment on that statement without knowing how fitness was assessed, since muscle is the organ with the greatest rate of glucose utilization. 

A second question that comes to my mind is whether or not lean type 2 diabetics are treated as aggressively or with the same regimens as the overweight/obese patients.   Increased cardiovascular risk is associated with certain classes of anti-diabetic agents, and physicians might view a type 2 diabetic with increased BMI as requiring more attention than one with normal weight.  It could be that lean patients weren’t followed as closely as obese diabetics and didn’t maintain the same degree of glycemic control, or that the lean diabetics were disproportionately treated with anti-diabetic agents associated with increased cardiovascular risk. 

I think that we’re not going to be able to adequately address this issue if we stick with our current diagnostic classification of both obesity and diabetes.  We’re already wrestling with this classification conundrum in the treatment of cancer. It’s been a long time coming, but the biomedical community now espouses the concept that not all cancers arising from the same cell type are identical.  While breast cancer may look the same under the microscope, we now appreciate that various mutations influence treatment regimens and prognosis.  Why then should we be surprised that complex metabolic disorders are any different? 

Is there an obesity paradox in type 2 diabetes?  That really isn’t the question.  Instead, we should focus on understanding the nuances of the disease, and its treatment that suggest there might be one.