Sweetening sixteen: Beyond the ominous octet

As the epidemic of type 2 diabetes continues to grow, newer pathophysiologic mechanisms of diabetes are being unraveled in quick succession. From a simplistic model of insulin deficiency and insulin resistance, researchers have moved to a multipronged explanation of the disease. In addition to the ominous octet, eight other players, such as catecholamines, vitamin D deficiency, renin–angiotensin system, testosterone deficiency, melatonin, renal gluconeogenesis, intestinal sodium-glucose cotransporter 1, and gut microbiota, seem to participate in the etiopathogenesis of glucose intolerance and type 2 diabetes. Collectively, these 16 players comprise a cluster of interrelated etiologies implicated in the pathogenesis of diabetes, prompting the authors to address them as the “sweetening sixteen.” While exploring these factors, the authors wish to emphasize that diabetes treatment should focus on the reversal of these proposed pathogenetic defects and not simply reduction of hemoglobin A1C.