Narrative Review
Basal insulin for the management of diabetic ketoacidosis

https://doi.org/10.1016/j.ejim.2017.08.025Get rights and content

Highlights

  • Basal insulin with regular insulin hastens ketoacidosis resolution and prevents hyperglycemia.

  • Basal insulin with regular insulin infusion was well tolerated.

  • This could potentially lead to a shorter ICU length of stay and reduced costs in the treatment of DKA.

Abstract

Due to its pharmacokinetic properties, it has been suggested that long-acting insulin analogues may have a role in facilitating the transition from continuous intravenous insulin infusion to subcutaneous maintenance therapy in patients with DKA for prevention of rebound hyperglycemia, particularly if there are high insulin requirements. Concomitant administration of basal insulin analogues with regular insulin infusion accelerates ketoacidosis resolution and prevents rebound hyperglycemia.

Several studies have investigated the use of basal insulin in the management of DKA. Studies have been instituted on pediatric patients and adult patients.

These studies reveal that co-administration of basal insulin in combination with an insulin infusion in the acute management of DKA is feasible.

Basal insulin co-administration with regular insulin infusion was well tolerated, associated with faster resolution of acidosis without any adverse effects; patients required a shorter duration of intravenous insulin infusion and had a lower total dose of intravenous insulin and significantly decreased hyperglycemia after discontinuation of the intravenous insulin. This could potentially lead to a shorter ICU length of stay and reduced costs in the treatment of DKA.

However, this approach may be associated with an increased risk of hypokalemia.

The current literature on this management approach is incomplete, due to its many limitations (retrospective nature, small sample size, nonrandomized design).

Additional prospective randomized studies are needed on this new therapeutic approach in the management patients with DKA.

Introduction

In the last decade, the mortality rate from diabetic ketoacidosis (DKA) has declined due to improvements in its management. The use of standardized written guidelines for therapy has resulted in a mortality rate lower than 5% [1], [2], [3], [4].

Long-acting insulin analogues enable a once-daily dosing in patients with diabetes mellitus (DM), thus providing a basal insulin component [5], [6].

Due to its pharmacokinetic properties, it has been suggested that this type of insulin may have a role in facilitating the transition from continuous intravenous (IV) insulin infusion to subcutaneous (SC) maintenance therapy in patients with DKA.

Transition from IV insulin infusion to SC insulin injections frequently results in rebound hyperglycemia, particularly if there are high insulin requirements. Furthermore, because of the short half-life of IV insulin, technical errors during the transitional phase of the insulin infusion can adversely affect the recovery process of DKA, specifically the occurrence of rebound hyperglycemia [7]. Extensive data indicate that uncontrolled hyperglycemia is associated with adverse outcomes in critically ill patients. For example, rebound hyperglycemia has the potential to increase the concentration of ketone bodies rather than decrease it, further delaying resolution of DKA and increasing length of stay in addition to increasing the risk of mortality and morbidity [7].

Concomitant administration of basal insulin analogues with regular insulin infusion accelerates ketoacidosis resolution and prevents rebound hyperglycemia [8].

Glargine, a soluble long-acting insulin analogue, exhibits physiological pharmacokinetic and pharmacodynamic characteristics [9]: it is a peakless insulin, that lasts for nearly 24 h, has lower intersubject variability compared with other types of intermediate- and long-acting insulins (such as Neutral Protamine Hagedorn – NPH – insulin, and Ultralente) and it closely mimics continuous subcutaneous insulin infusion (CSII), the gold standard of basal insulin replacement [10].

Therefore, the use of basal insulin such as glargine may be associated with several beneficent effects in the management of patients with DKA.

Several studies have investigated the use of basal insulin in the management of DKA. Studies have been instituted on experimental investigations, and have been performed using animal models (cats), pediatric patients and adult patients.

The addition of long-acting insulin during IV insulin infusion for treatment of DKA appears to be safe, as the number of hypoglycemic events does not differ [7].

Section snippets

Animal models

There are several studies on animal models confirming the usefulness of the management of DKA with basal insulin.

Gallagher BR et al. performed a pilot study comparing a protocol using intermittent administration of glargine and regular insulin to a continuous rate infusion of regular insulin in cats with naturally occurring DKA. The authors concluded that intermittent short- and long-acting insulin injection was useful for the treatment of cats with DKA [11].

In another study, Marshall RD et al.

Pediatric patients

Shankar V et al. studied the effect of subcutaneous administration of insulin glargine in the early phase of DKA on the rate of resolution of acidosis and intravenous insulin infusion requirement in children with moderate and severe diabetic ketoacidosis.

This was a retrospective cohort trial of 71 pediatric patients with moderate and severe DKA, during which 12 patients received 0.3 units/kg of subcutaneous insulin glargine within 6 h of admission and 59 were treated following a standard protocol

Adult patients

Hsia E et al. performed a prospective, randomized, controlled study of 61 diabetic patients, comparing 31 patients treated with regular insulin infusion and 30 patients treated with regular insulin infusion plus 0.25 U/kg of daily glargine [9]. It is important to note that only 25 patients in this study had DKA and all subjects with DKA had DM type 1. The remainder of patients received intravenous insulin for postoperative management of diabetes after kidney, liver, or lung transplantation (n = 

Conclusions

Co-administration of basal insulin in combination with an insulin infusion in the acute management of DKA is feasible.

Basal insulin co-administration with regular insulin infusion was well tolerated, associated with faster resolution of acidosis without any adverse effects; patients required a shorter duration of intravenous insulin infusion and had a lower total dose of intravenous insulin and significantly decreased hyperglycemia after discontinuation of the intravenous insulin. This could

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