Background: Eight percent of the U.S. population has been diagnosed with diabetes mellitus (DM), while another large percentage has gone undiagnosed. As the epidemiology of this disease constitutes a larger percentage of the American population, another factor presents a dangerous dilemma that can exacerbate the hazardous effects imposed by DM. Excessive alcohol consumption concerns the health of more than 50% of all adults. When this heavy-alcohol-drinking population overlaps with DM and its complications, the effects can be dangerous. In this review, we term it as "double trouble." Methods: We provide evidence of alcohol-induced exacerbation of organ damage in diabetic conditions. In certain cases, we have explained how diabetes and alcohol induce similar pathological effects. Results: Known exacerbated complications include those related to heart diseases, liver damage, kidney dysfunction, as well as retinal and neurological impairment. Often, pathophysiological damage concludes with end-stage disorders and even mortality. The metabolic, cell signaling, and pathophysiological changes associated with "double trouble" would lead to the identification of novel therapeutic targets. Conclusions: This review summarizes the epidemiology, diagnosis, pathophysiology, metabolic, and cell signaling alterations and finally brushes upon issues and strategies to manage the "double trouble".
