IMPE Abstracts

Over the last two decades, there has been a major expansion in agents targeting contributors to metabolic dysfunction in type 2 diabetes. Modern pharmacologic agents have allowed clinicians to move beyond reduction in glycemia as the primary treatment target and to begin to select agents based on more individualized aspects of dysfunction unique to each patient. The potency of this approach is demonstrated by the changing outcomes landscape for adult individuals with type 2 diabetes treated with physiology-based multi-agent therapy. Current adult therapy pairs glucose normalization with leveraging of pathways to facilitate improvements in adiposity, hepatic dysfunction, cardiac and vascular dysfunction, dyslipidemia, and other associations with insulin resistance. Most exciting, there are finally treatment approaches that reduce risk for cardiac and, most exciting, there are finally treatment approaches that reduce hard cardiac and renal events, the real killers in type 2 diabetes. Given the success of these agents in adults, it is tempting to apply these results to youth and initiate treatment with agents approved in adults but not yet in the pediatric population. However, there is a strong argument for caution. It has been clearly demonstrated that youth-onset type 2 diabetes differs from its adult counterpart in several ways. Youth-onset type 2 shows more severe insulin resistance, generally more rapid progression of beta-cell dysfunction, differences in insulin clearance, important sex-related differences not seen in adults, and more rapid accumulation of complications. These differences suggest that treatment responses may differ between youth and adults and already we have seen outcomes of clinical trials completed to-date of these agents that confirm this suspicion, with less efficacy and impact on weight than seen in adults. Indeed, sitagliptin, a widely prescribed medication in adults, was not shown to be better than placebo in youth in a rigorously preformed trial. These differences in pathophysiology and effects in trials reported so far suggest the need for discretion in prescribing these exciting agents before there is sufficient data to warrant approval. Fortunately, the quickening pace of reports of trials in youth promises that the wait may not be much longer.