Subcutaneous insulin may be cutting edge in the treatment of diabetics, but studies show that its benefits over old fashioned IV insulin are marginal at best.
Diabetic ketoacidosis (DKA) remains one of the more serious complications of diabetes. DKA management usually involves the continuous infusion of intravenous regular insulin, as recommended by both the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes.
Studies conducted in the 1970s and 1980s demonstrated the superiority of IV regular insulin over subcutaneous (SC) or intramuscular (IM) regular insulin, with a more rapid initial decrease in plasma glucose and ketone levels observed (Fisher 1977). These observations are likely due to the relatively prolonged half-life of SC and IM regular insulin. Newer, rapid-acting insulin analogues (aspart and lispro) offer the advantage of having much shorter half-lives than regular insulin, and their efficacy in the management of DKA, when administered subcutaneously, is worth reviewing.
The main issue with IV insulin drips is that, in most institutions, their use requires admission to an ICU setting. Unfortunately, as our patient population ages and as life-prolonging treatments become more commonplace, ICU beds are getting harder to come by. As a result, DKA patients are sometimes managed in the emergency department until their anion gap closes and the insulin drip can be turned off. Management of such patients in the ED ties up precious space for hours, or even days, increasing wait times for other potentially ill patients. Therefore, a treatment strategy that can be performed on a general medical ward would be a valuable way to free up ICU and/or ED beds for other patients. SC insulin offers this advantage, at least in theory.
In the last decade, five small randomized, controlled trials have been published assessing the utility of SC, fast-acting insulin in the management of DKA. These studies have evaluated a wide range of patient populations, from adults to pediatrics, at academic US centers compared to those in Brazil and India, and those with DKA of varying severity (See Table 1). All of these studies have shown that SC insulin is safe and effective, compared to continuous IV insulin, in the treatment of DKA. These studies have demonstrated similar durations of treatment required to control hyperglycemia and to resolve DKA, without an increase in hypoglycemic events or recurrent DKA.
Why then, in light of this evidence, have we not abandoned insulin drips in uncomplicated cases of DKA? The answer is in the details. When considering the benefits of one route over another, there was no advantage in terms of duration of treatment or the frequency of adverse events. There were rare occurrences of hypoglycemia with both SC and IV insulin observed in all of the studies, with similar frequency seen for both routes. None of the studies reported any recurrence of DKA during hospital admission, and there was no mortality. Long-term outcomes were not reported, but would be expected to be similar, given the similar reductions in blood sugar, ketosis, and acidosis observed. The ability of SC insulin to effectively manage DKA, and to do so without increased harm, is therefore not in question.
One study did observe a significant cost difference, with a 39% mean reduction in hospital cost with the use of SC insulin. However, this observation has been attributed to the study’s protocol, whereby all patients in the IV group were admitted to the ICU, while patients in the SC group were admitted either to the floor or to an “intermediate care” unit. The cost difference, therefore, was likely due to the ICU charge itself (Haas 2004). Had all patients in the study been managed in the same setting, the costs would likely have been similar. As the study did not prove that ICU admission is necessary when treating DKA with IV insulin, but unnecessary when SC insulin is used, this cost difference must be attributed to the study protocol.
So, instead, we should consider two other factors: the amount of bedside nursing care required and patient satisfaction. As none of the studies assessed these outcomes, we must rely on conjecture. The only difference in management between the groups was in the administration of the insulin. All of these studies’ protocols involved the hourly (or every other hour) administration of SC, fast-acting insulin in lieu of a continuous IV infusion. The patients in the SC insulin groups in these studies still required hourly, or every other hour, blood sugar checks in addition to usual fluid administration. It seems unlikely, therefore, that the use of SC insulin would actually reduce the amount of nursing care required. In fact, one could argue that the time required to set up and adjust the pump for an insulin drip may be less than the time required to draw up and administer a shot of insulin every hour, or even every other hour.
Patient satisfaction also was not addressed in any of these studies. Not surprisingly, phlebotomy surveys have revealed that patient satisfaction decreases with an increasing number of needle sticks required to obtain blood. While a SC injection is different from the needle stick associated with phlebotomy, it seems reasonable to conclude that an increased number of SC injections would result in increased pain and decreased satisfaction. The use of every other hour SC insulin in these studies would result in 5-6 injections over a 10-12 hour period in order to achieve resolution of DKA. As the patient, many would likely prefer an insulin drip to the frequent injections required by this alternate therapy.
Given that SC insulin likely does not decrease the amount of nursing care required (and may actually increase it), it seems illogical to surmise that its use will obviate the need for ICU level care. Obtaining hourly, or every other hour, blood sugar checks while simultaneously administering an insulin injection every 1-2 hours is unlikely to occur in the general medical wards of most hospitals. In a retrospective chart review of patients receiving SC insulin aspart every two hours at Rush University Medical Center in Chicago, the average ICU length of stay was nearly 44 hours (Teevan 2012). The ICU length of stay reported is similar to values seen when a SC insulin protocol is not in use (Freire 2002). This protocol does not seem to keep these patients from being admitted to the ICU, or reduce their ICU length of stay, at least at this one institution.
While emergency physicians are known for their versatility, adaptability, and trailblazing capabilities, this is one situation where traditional care wins out. While subcutaneous insulin does appear to be a safe and effective alternative to continuous IV insulin in the management of DKA, its benefit is much less apparent. Its use will likely remain relegated to situations where an insulin drip is simply not possible. For the other 99% of the time, good old-fashioned IV insulin is the way to go.
Kitabchi AE, Umpierrez GE, Murphy MB, et al; American Diabetes Association. Hyperglycemic crises in diabetes. Diabetes Care. 2004 Jan;27 Suppl 1:S94-102.
Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis in children and adolescents with diabetes. Pediatr Diabetes. 2009 Sep;10 Suppl 12:118-33.
Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med 297:238 –241, 1977
Umpierrez GE, Cuervo R, Karabell A, Latif K, Freire AX, Kitabchi AE. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004 Aug;27(8):1873-8.
Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004 Sep 1;117(5):291-6.
Della Manna T, Steinmetz L, Campos PR, et al. Subcutaneous use of a fast-acting insulin analog: an alternative treatment for pediatric patients with diabetic ketoacidosis. Diabetes Care. 2005 Aug;28(8):1856-61.
Ersöz HO, Ukinc K, Köse M, et al. Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients. Int J Clin Pract. 2006 Apr;60(4):429-33.
Karoli R, Fatima J, Salman T, Sandhu S, Shankar R. Managing diabetic ketoacidosis in non-intensive care unit setting: Role of insulin analogs. Indian J Pharmacol. 2011 Jul;43(4):398-401.
Haas RM, Hoffman AR. Treatment of diabetic ketoacidosis: should mode of insulin administration dictate use of intensive care facilities? Am J Med. 2004 Sep 1;117(5):357-8.
Teevan C. Evaluation of a diabetic ketoacidosis treatment protocol using subcutaneous insulin aspart. Crit Care Med. 2012 Dec; 40(12):1-328.
Freire AX, Umpierrez GE, Afessa B, Latif KA, Bridges L, Kitabchi AE. Predictors of intensive care unit and hospital length of stay in diabetic ketoacidosis. J Crit Care. 2002 Dec;17(4):207-11.
Dr. Cohn practices emergency medicine at Washington University in St. Louis. He is the director of the Washington University EM Journal Club and the voice of the EMJClub podcast.