New approaches to the use of insulin in patients with diabetic ketoacidosis

Barski, Leonid; Kezerle, Louise; Zeller, Lior; Zektser, Miri; Jotkowitz, Alan

doi:10.1016/j.ejim.2013.01.014

Cited by 23 publications

(14 citation statements)

References 40 publications

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“…Insulin analogs glulisine, aspart and lispro have been reported to have equal efficacy and in vivo potency compared to regular insulin in animals and humans, attributable to their similar receptor binding affinity and receptor mediated clearance (50–53), although only studies comparing the role of intravenous glulisine infusion as an alternative to intravenous infusion of regular human insulin has been performed (54). In spite of their more rapid onset, studies comparing the pharmacokinetics and pharmacodynamics of intravenous glulisine (an ultrashort-acting insulin analogue) to intravenous regular insulin (short-acting insulin) have found glulisine demonstrates equivalent glucose utilisation and disposal; and a similar distribution and elimination profile to regular insulin (50, 54).…”

Section: Resultsmentioning

confidence: 99%

“…In spite of their more rapid onset, studies comparing the pharmacokinetics and pharmacodynamics of intravenous glulisine (an ultrashort-acting insulin analogue) to intravenous regular insulin (short-acting insulin) have found glulisine demonstrates equivalent glucose utilisation and disposal; and a similar distribution and elimination profile to regular insulin (50, 54). …”

Section: Resultsmentioning

confidence: 99%

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Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols

et al. 2017

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BackgroundDiabetic ketoacidosis (DKA) is an endocrine emergency with associated risk of morbidity and mortality. Despite this, DKA management lacks strong evidence due to the absence of large randomised controlled trials (RCTs).ObjectiveTo review existing studies investigating inpatient DKA management in adults, focusing on intravenous (IV) fluids; insulin administration; potassium, bicarbonate, and phosphate replacement; and DKA management protocols and impact of DKA resolution rates on outcomes.MethodsOvid Medline searches were conducted with limits “all adult” and published between “1973 to current” applied. National consensus statements were also reviewed. Eligibility was determined by two reviewers’ assessment of title, abstract, and availability.ResultsA total of 85 eligible articles published between 1973 and 2016 were reviewed. The salient findings were (i) Crystalloids are favoured over colloids though evidence is lacking. The preferred crystalloid and hydration rates remain contentious. (ii) IV infusion of regular human insulin is preferred over the subcutaneous route or rapid acting insulin analogues. Administering an initial IV insulin bolus before low-dose insulin infusions obviates the need for supplemental insulin. Consensus-statements recommend fixed weight-based over “sliding scale” insulin infusions although evidence is weak. (iii) Potassium replacement is imperative although no trials compare replacement rates. (iv) Bicarbonate replacement offers no benefit in DKA with pH > 6.9. In severe metabolic acidosis with pH < 6.9, there is lack of both data and consensus regarding bicarbonate administration. (v) There is no evidence that phosphate replacement offers outcome benefits. Guidelines consider replacement appropriate in patients with cardiac dysfunction, anaemia, respiratory depression, or phosphate levels <0.32 mmol/L. (vi) Upon resolution of DKA, subcutaneous insulin is recommended with IV insulin infusions ceased with an overlap of 1–2 h. (vii) DKA resolution rates are often used as end points in studies, despite a lack of evidence that rapid resolution improves outcome. (viii) Implementation of DKA protocols lacks strong evidence for adherence but may lead to improved clinical outcomes.ConclusionThere are major deficiencies in evidence for optimal management of DKA. Current practice is guided by weak evidence and consensus opinion. All aspects of DKA management require RCTs to affirm or redirect management and formulate consensus evidence-based practice to improve patient outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols

et al. 2017

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“…7,8 However, daily administration of insulin by injection is uncomfortable for patients and can even be dangerous: the injection of excess insulin can result in serious shock responses such as hypoglycemia, syncope, or even death. 9,10 To ameliorate these issues, much effort has been invested in the development of smart drug delivery systems that are able to release insulin in response to changes in the blood glucose level. A significant number of reports of glucose-sensitive systems have emerged in the literature over the last decade or so.…”

Section: Introductionmentioning

confidence: 99%

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Wu¹,

Williams²,

Li³

et al. 2017

IJN

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Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid- b -diethylene glycol methyl ether methacrylate); p(AAPBA- b -DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1 H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA- b -DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.

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“…Few studies, mostly in adults, demonstrated subcutaneous rapid acting insulin injected every 1-2 h to be a valid alternative for the standard intravenous insulin treatment of mild-tomoderate uncomplicated DKA [79,80]. In our practice, we administer subcutaneous regular insulin (SCRI) every 4 h for treating children with DKA and pH ≥7.00 and K >2.5 mEq/L.…”

Section: Subcutaneous Insulin Regimensmentioning

confidence: 99%

Diabetic Ketoacidosis in the Pediatric Population with Type 1 Diabetes

Cohen¹,

Shilo²,

Zuckerman‐Levin³

et al. 2015

Major Topics in Type 1 Diabetes

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Diabetic ketoacidosis DK" is a leading cause of morbidity and mortality in patients with type diabetes T DM . Individuals familiar with this complication of diabetes should be able to identify the earliest signs and symptoms and act promptly to prevent further deterioration. However, even in patients with established diabetes, the rates of DK" are considerable. This chapter discusses in detail the various aspects of DK" in the pediatric population with T DM. The prevalence and regional effects on the prevalence of DK" as well as the specific risk factors, whether disease, patient, or physician related, are reviewed. Patients with DK" experience a condition of starvation despite the abundance of metabolic substrate i.e., glucose the pathophysiological mechanisms responsible for the development of DK" are outlined. Next, a detailed discussion of the clinical aspects of DK" is provided. This includes the clinical findings at presentation, the approach to treatment, and potential complications. Prevention is the best method for reducing rates of DK". Somewhat different factors apply in patients with new-onset diabetes when compared with those with established diabetes and these are reviewed.

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New approaches to the use of insulin in patients with diabetic ketoacidosis

Cited by 23 publications

References 40 publications

Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols

Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Diabetic Ketoacidosis in the Pediatric Population with Type 1 Diabetes

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