If Obesity Is A Disease, What’s The Disease Process?

Obesity, defined as the presence of abnormal or excess body fat that impairs health, by definition, impairs health and is increasingly recognised as a chronic disease not unlike hypertension or diabetes.

But what exactly is the disease process?

Here an analogy with chronic kidney disease may be helpful.

For one, like chronic kidney disease, obesity can have a wide range of different underlying drivers. These can be genetic, environmental, iatrogenic (medications), or some other (unrelated) disease process.

Thus, in the same way that chronic kidney disease can result from polycystic kidney disease (genetic), lead toxicity (environmental), non-steroidal anti-inflammatory drugs (medications), or plasmocytoma (unrelated disease), obesity can result from Prader-Willi syndrome (genetic), highly processed foods (environmental), atypical anti-psychotics (medications), or craniopharyngioma (unrelated disease).

In kidney disease, each of these causes have different disease pathways, timelines, and prognosis, the end result, however, is an often progressive and irreversible loss of kidney function, which in extreme cases can end with the patient needing renal replacement therapy (like dialysis of kidney transplant).

Similarly, irrespective of the underlying cause, obesity, once established, generally becomes a life-long problem, which can often progress over time and may, in extreme cases, result in terminal incapacitating illness.

Secondly, irrespective of the underlying cause, chronic kidney disease, like obesity, can result in a wide range of associated disease processes.

Thus, irrespective of the underlying cause, progressive loss of kidney function results in a common pathway of related disease processes that can lead to fluid retention, hypertension, anemia, hyperparathyroidism, bone disease, and increased risk for infections and cardiovascular complications.

Similarly, irrespective of the underlying cause, progressive accumulation of abnormal or excessive body fat can result in a range of related disease processes ranging from metabolic problems (type 2 diabetes, gout, dyslipidemia, fertility issues), to mechanical issues (obstructive sleep apnea, GERD, plantar fasciitis, gonarthritis, urinary incontinence), to cancers (endometrial, breast, colon).

In addition, both chronic kidney disease and obesity can significantly affect overall physical and emotional well-being and quality of life.

As in chronic kidney disease, the exact processes by which obesity affects various aspects of health are distinct and involve specific pathophysiological pathways.

Thus, in the same way that we now understand how loss of kidney function can result in complications like anemia (loss of erythropoietin) or hyperparathyroidism (loss of activation of Vitamin D), we understand how accumulation of abnormal or excess body fat can lead to type 2 diabetes (reduced levels of adiponectin and increased intramyocellular lipid accumulation leading to insulin resistance) or obstructive sleep apnea (increased pharyngeal fat accumulation).

As in chronic kidney disease, not every patient with obesity develops every possible complication. Thus, for e.g. in the same way that not every patient with chronic kidney disease develops hypertension or bone disease, not every patient with obesity necessarily develops type 2 diabetes or sleep apnea.

In summary, as in patients with chronic kidney disease, where we now appreciate that irrespective of the different causal pathways leading to the loss of kidney function, there are discrete common pathways leading to typical complications, in patients presenting with obesity, irrespective of the wide range of pathways that can lead to the accumulation of abnormal or excessive body fat, there are discrete common pathways leading to the typical complications associated with obesity.

Incidentally, this view of obesity has important clinical consequences. Thus, as in patients with chronic kidney disease, obesity management had three distinct goals, each of which may require a different management strategy:

1. Addressing the underlying drivers
2. Halting or slowing progression
3. Preventing or managing the complications

@DrSharma
Busan, South Korea