Leveraging Mechanical Forces to Target Insulin Injection–Induced Lipohypertrophy and Fibrosis

As of 2017, more than 30 million Americans—nearly 10% of the population—have diabetes (1). More than 1.5 million new cases of diabetes were diagnosed in 2015 (1). The prevalence of both type 1 and type 2 diabetes is rapidly increasing, and by 2050, diabetes is expected to affect more than one in five adults in the United States (2–5). The economic burden of diabetes is enormous and growing; in 2017, it was estimated to be $327 billion, including $237 billion in direct medical costs (6), a nearly twofold increase from 2007 (3). The 1.25 million American adults living with type 1 diabetes comprise 5.6% of all U.S. adults with a diabetes diagnosis (7). Because these patients are unable to produce sufficient endogenous insulin, they are reliant on exogenous insulin injections for their entire lives. In addition to individuals with type 1 diabetes, roughly 30% of patients with type 2 diabetes also require insulin therapy, typically in the setting of A1C levels that are uncontrolled with oral hypoglycemic agents (8–11). Recently, exorbitant insulin prices have dominated news headlines across the United States. In just 5 years, from 2012 to 2017, the cost of insulin increased by 110% (6). Insulin costs totaled more than $14 billion in 2017, not including required supplies and equipment, which were responsible for an additional $5 billion in costs (6). Beyond the sizeable economic burden of insulin use, long-term insulin administration can also cause a host of problems for patients. In particular, repeated insulin injections and insulin pump use often result in complications and changes in the skin at injection or pump sites (Figure 1) (12). The two most common injection site complications are: 1. Fibrosis, the accumulation of stiff, dense scar tissue at the injection site (Figure 1 A , middle …