Rebound Hyperglycemia Research Articles

Mechanism and performance of choline-based ionic liquids in enhancing nasal delivery of glucagon

Proteins and peptides have been increasingly developed as pharmaceuticals owing to their high potency and low side effects. However, their administration routes are confined to injections, such as intra-muscular and intra-venous injections, making patient compliance a challenge. Hence, non-injectable delivery systems are crucial to expanding the clinical use of proteins and peptides. In this context, two choline-based ionic liquids (ILs), namely, choline geranic acid ([Ch][Ger]) and choline citric acid ([Ch][Cit]), have been identified as promising agents for enhancing the permeation and prolonging the retention time of glucagon (GC) after intra-nasal administration. Notably, intra-nasal delivery of GC via ILs (GC/ILs) elicited rapid and smooth reversal of acute hypoglycaemia without leading to rebound hyperglycaemia in type 1 diabetic rats subjected to insulin induction. In addition, ILs could improve the transcellular transport of GC through electrostatic interaction. ILs could also transiently open inter-cellular tight junctions transiently to facilitate the paracellular transport of GC. Safety tests indicated that continuous intra-nasal delivery of ILs led to reversible changes, such as epithelial cell inflammation, goblet cell overgrowth, and impacts on the distribution of nasal cilia. However, these changes could be alleviated by the innate self-repair ability of mucosal epithelial cells. This study highlights the considerable potential of ILs for long-term nasal delivery of biomacromolecules.

Frequency of Rebound Hyperglycemia in Adults with Type 1 Diabetes Treated with Different Insulin Delivery Modalities.

Background: For people with type 1 diabetes (T1D), ensuring fast and effective recovery from hypoglycemia while avoiding posthypoglycemic hyperglycemia (rebound hyperglycemia, RH) can be challenging. The objective of this study was to investigate the frequency of RH across different treatment modalities and its impact on glycemic control. Methods: This cross-sectional real-world study included adults with T1D using continuous glucose monitoring and attending the outpatient clinic at Steno Diabetes Center Copenhagen. RH was defined as ≥1 sensor glucose value (SG) >10.0 mmol/L (180 mg/dL) starting within 2 h of an antecedent SG <3.9 mmol/L (70 mg/dL). The severity of the RH events was calculated as area under the curve (AUC) and separately for users of multiple daily injections (MDIs), unintegrated insulin pumps, sensor augmented pumps (SAPs), and automated insulin delivery (AID), respectively. Results: Across the four groups, SAP and AID users had the highest incidence of RH (2.06 ± 1.65 and 2.08 ± 1.49 events per week, respectively) and a similar percentage of hypoglycemic events leading to RH events (41.3 ± 22.8% and 39.6 ± 20.1%, respectively). The AID users with RH events were significantly shorter compared with MDI users (122 ± 72 vs. 185 ± 135 min; P < 0.0001). Overall, severity of RH was inversely associated with more advanced technology (P < 0.001) and inversely associated (P < 0.001) with time in target range (TIR). Conclusions: Groups with insulin suspension features experienced the highest frequency of RH; however, AID users tended to experience shorter and less severe RH events. The association between the severity of RH events and TIR suggests that RH should be assessed and used in the guidance of hypoglycemia management.

Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes?

Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition. This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts. We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups. Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers.

Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) severe iatrogenic hypoglycemia followed by rebound hyperglycemia. Methods: Two iatrogenic hypoglycemia studies were compared; firstly, mild hypoglycemia in 18 subjects (10 type 2 diabetes (T2D), 8 controls; blood glucose to 2.8 mmoL/L (50 mg/dL) for 1 h), and secondly, severe hypoglycemia in 46 subjects (23 T2D, 23 controls; blood glucose to <2.2 mmoL/L (<40 mg/dL) transiently followed by intravenous glucose reversal giving rebound hyperglycemia). A SOMAscan assay was used to measure 54 of the 92 cardiovascular protein biomarkers that reflect biomarkers involved in inflammation, cellular metabolic processes, cell adhesion, and immune response and complement activation. Results: Baseline to euglycemia showed no change in any of the proteins measured in the T2D cohort. With severe hypoglycemia, the study controls showed an increase in Angiopoietin 1 (ANGPT1) (p < 0.01) and Dickkopf-1 (DKK1) (p < 0.01), but no changes were seen with mild hypoglycemia. In both the mild and severe hypoglycemia studies, at the point of hypoglycemia, T2D subjects showed suppression of Brother of CDO (BOC) (p < 0.01). At 1 h post-hypoglycemia, the changes in ANGPT1, DKK1, and BOC had resolved, with no additional protein biomarker changes despite rebound hyperglycemia from 1.8 ± 0.1 to 12.2 ± 2.0 mmol/L. Conclusions: Proteomic biomarkers of cardiovascular disease showed changes at hypoglycemia that resolved within 1 h following the hypoglycemic event and with no changes following hyperglycemia rebound, suggesting that any cardiovascular risk increase is due to the hypoglycemia and not due to glucose fluctuation per se.

Pilot Study on the Impact of Early Subcutaneous Basal Insulin Administration in Diabetic Ketoacidosis.

Purpose/Background: Recent studies have shown improved outcomes with the initiation of earlier subcutaneous (SQ) basal insulin. The purpose of this study was to examine the effects of early SQ basal insulin administration on hospital length of stay in patients with mild to moderate diabetic ketoacidosis (DKA). Methods: This was a retrospective, single-center study from a large community teaching hospital that included patients 18 years or older with mild to moderate DKA, identified using ICD-10 codes, who received intravenous (IV) insulin. Patients who received SQ basal insulin prior to a documented anion gap ≤12 mmol/L were considered to have received early SQ basal insulin and were compared to patients who received SQ basal insulin after closure of their anion gap (AG). The primary outcome was hospital length of stay. Secondary outcomes included intensive care unit length of stay, duration of IV insulin, time to anion gap closure, and incidences of rebound hyperglycemia. Safety outcomes included incidences of hypoglycemia, and hypokalemia. Results: Of 301 patients screened, 108 patients were included in the final analysis. Forty patients received early SQ basal insulin and 68 did not. Median hospital length of stay in the nonearly group was 71 h, compared to 62 h in the early group (P = .57). Secondary and safety outcomes were similar between groups. Conclusions: In this study, there was no statistically significant difference in length of stay in patients that received early SQ basal insulin. Larger trials are needed to determine the significance of earlier SQ basal insulin in DKA.

Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies. Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: P = .0047; 1-4 hours: P = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: P = .0034; 1-4 hours: P = .0068). iAUC and AUC were lower with NG vs IG (P = .025 and P < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies. This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG. NCT03421379, NCT03339453, NCT01994746.

FRI642 The Effect Of Early Basal Insulin Administration On Diabetic Ketoacidosis (DKA) Management

Abstract Disclosure: H. Al-Marsumi: None. S.Z. Pollack: None. N. Simon: None. Background: DKA and HHS are considered serious acute complications of diabetes and constitute endocrine emergencies. Management of DKA and HHS consists of fluid, potassium replacement and weight-based adjusted rate intravenous insulin infusion, with close monitoring of capillary glucose, serum electrolytes, venous PH, and Beta-hydroxybutyrate. Current Standard DKA management protocols introduce and overlap subcutaneous insulin with intravenous insulin infusion after anion gap closure. In United states, few studies looked at different outcomes after early administration of basal insulin (i.e. before anion gap closure) during DKA management. Objective: The purpose of this research is to study the effect of early administration of basal long-acting insulin in addition to intravenous insulin on the time to anion gap closure, incidence of rebound hyperglycemia, hypoglycemia, transitional failure, length of ICU stays and length of Hospital stays, compared to intravenous insulin infusion only. Methods: This was a single-center, retrospective chart review study of adults 21 years or older admitted to the hospital with DKA diagnosis between September 2020 and May 2022. The patients were divided into two groups (Study group which includes those with early administration of basal long-acting insulin in addition to intravenous insulin infusion and Standard group which includes patients who received intravenous insulin infusion only). The primary outcome was the time to anion gap closure. The other outcomes included incidence of rebound hyperglycemia, hypoglycemia, transitional failure, length of ICU stay, as well as the length of hospital stay. Results: A total of 231 admissions were included for analysis; 29 patients were included in the (Study group) and 202 in the (Standard group). The mean time ± standard deviation for hours till anion gap closure in the study group and standard group were (21.3938 ± 25.2603 and 12.7679 ± 9.3512) respectively showing no statistical difference between the two groups with a P value of 0.0789. The incidence of hypoglycemia was 21% in the study group and 24% in the standard group with P value of 0.8173. There was no statistical difference in length of ICU stays, length of hospital stays, incidence of rebound hyperglycemia, transitional failure between the study and control groups with a p value of (0.3867, 0.7207, 0.7758 and 0.1387) respectively. Conclusion: There was no statistical difference in time to anion gap closure, length of ICU stays, length of hospital stays, incidence of rebound hyperglycemia, hypoglycemia, transitional failure between the study and Standard groups. Further Studies are needed to evaluate the effect of early basal insulin administration on DKA management. Presentation: Friday, June 16, 2023

What are we waiting for? A review of early basal insulin therapy in diabetic ketoacidosis management

Diabetic ketoacidosis (DKA) remains a significant challenge for healthcare systems due to prolonged lengths of stay and rising costs. The current American Diabetes Association (ADA) guidelines recommend starting basal insulin after resolution of DKA. However, these guidelines have not been updated since 2009, which can potentially limit optimal care. Meanwhile, the Joint British Society guidelines on DKA management, which were more recently updated in March 2023, do advocate for early administration of basal insulin in their treatment algorithm. This article assesses the rationale and literature associated with the recommendation for early basal insulin administration in the management of DKA. Benefits of early basal insulin in this cohort appears to be associated with less rebound hyperglycemia, reduction in time to DKA resolution, reduced intravenous insulin requirements, and reduced length of stay without associated increases in hypoglycemic or hypokalemic events.

380-P: Towards Prevention of Nonsevere Hypoglycemia in Type 1 Diabetes with Oral Glucose at a Higher Blood Glucose Threshold—The REVERSIBLE Trial

Background: Current guidelines recommend initiating the treatment of non-severe (NS) hypoglycemia with 15g of carbohydrates (CHO) at 15 minutes intervals when blood glucose (BG) reaches &amp;lt;72 mg/dl. Despite this recommendation, NS hypoglycemia management remains challenging for people living with type 1 diabetes (pwT1D) and more optimal treatment strategies are required. We aim to assess the efficacy of 15g of CHO at higher treatment thresholds. Methods: The REVERSIBLE Trial is an open-label, randomized, three interventions x three periods cross-over study. Following inpatient insulin-induced decrease in BG, 16g of oral carbohydrates is administered at a plasma glucose threshold of &amp;lt;72 mg/dl, ≤81 mg/dl or ≤90 mg/dl. The primary outcome is the time (in minutes) spent in hypoglycemia (&amp;lt;72 mg/dl) after the initial correction. Results: Participants (n=29) characteristics are 52% male, 46.8±16.3 years old, BMI of 26.4±3.9 kg/m2, diabetes duration of 26.2±15.9 years, A1c of 53.4±15.5 mmol/mol and 62% insulin pump users. When comparing &amp;lt;72 mg/dl (control) to ≤81 mg/dl and ≤90 mg/dl treatment thresholds, 100% vs. 86% (p=0.1201) vs. 34% (p&amp;lt;0.0001) of participants had hypoglycemia. These hypoglycemic events lasted 26.0±12.6 vs. 17.9±14.7 (p=0.026) vs. 7.1±11.8 (p=0.002) minutes, with a blood glucose nadir of 56.5±9.9 vs. 63.5±7.9 (p=0.008) vs. 73.4±9.7 mg/dl (p=0.002) respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥ 72 mg/dl) compared to 52% in the ≤81 mg/dl group and 31% in the ≤90 mg/dl group with no significant rebound hyperglycemia (&amp;gt;180mg/dl) within the first hour. Conclusion: Compared with &amp;lt;72 mg/dl, consuming 16g of oral carbohydrates at ≤81 mg/dl and ≤90 mg/dl shortened the time spent in hypoglycemia, lessened the glucose nadir and reduced the need for repetitive treatments. For some NS episodes, pwT1D could benefit from CHO intake at a higher BG threshold. Disclosure R.Cheng: None. N.Taleb: Consultant; Viatris Inc. Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)

‘You have to use everything and come to some equilibrium’: a qualitative study on hypoglycemia self-management in users of continuous glucose monitor with diverse hypoglycemia experiences

IntroductionAlthough continuous glucose monitoring systems (CGMs) can help reduce hypoglycemia, about one-quarter of people with type 1 diabetes (T1D) who use CGMs still either spend at least 1% of the...

Rebound Hypoglycemia and Hyperglycemia in Type 1 Diabetes.

The aim was to investigate rebound hypoglycemic and hyperglycemic events, and describe their relation to other glycemic metrics. Data from intermittently scanned continuous glucose monitoring were downloaded for 90 days for 159 persons with type 1 diabetes. A hypoglycemic event was defined as glucose <3.9 mmol/l for at least two 15-minute periods. Rebound hypoglycemia (Rhypo) was a hypoglycemic event preceded by glucose >10.0 mmol/l within 120 minutes and rebound hyperglycemia (Rhyper) was hypoglycemia followed by glucose >10.0 mmol/l within 120 minutes. A total of 10 977 hypoglycemic events were identified of which 3232 (29%) were Rhypo and 3653 (33%) were Rhyper, corresponding to a median frequency of 10.1, 2.5, and 3.0 events per person/14 days. For 1267 (12%) of the cases, Rhypo and Rhyper coexisted. The mean peak glucose was 13.0 ± 1.6 mmol/l before Rhypo; 12.8 ± 1.1 mmol/l in Rhyper. The frequency of Rhyper was significantly (P < .001) correlated with Rhypo (Spearman's rho 0.84), glucose coefficient of variation (0.78), and time below range (0.69) but not with time above range (0.12, P = .13). The strong correlation between Rhyper and Rhypo suggests an individual behavioral characteristic toward intensive correction of glucose excursions.

Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon

ObjectivesSelf-management guidelines for nonsevere hypoglycemia (NS-H) in type 1 diabetes recommend 15 g of simple carbohydrates (CHO) at 15-minute intervals. Because automated insulin delivery (AID) preventively reduces or suspends insulin infusion for imminent hypoglycemia, we aimed to determine whether guidelines were excessive during AID. MethodsThis work was a secondary analysis of NS-H episodes during inpatient single-hormone (insulin) or dual-hormone (insulin and glucagon) AID trials with standardized CHO treatment protocols. ResultsForty NS-H episodes occurred: 15 during single-hormone arms (2 trials) and 25 during dual-hormone arms (5 trials). At NS-H treatment T0min, plasma glucose (PG) level was 3.1±0.6 mmol/L, corresponding to a sensor value of 3.6±0.6 mmol/L. Fifteen minutes after CHO consumption, PG increased by 0.9±0.8 mmol/L, recovering 45% of episodes to a safe PG of ≥4.0 mmol/L. With repeated CHO consumption, time to recovery was 21.4±15.7 minutes without rebound hyperglycemia; PG 1 hour after initial CHO was 5.9±2.0 mmol/L. Outcome differences between single-hormone and dual-hormone systems were not statistically significant, except for higher insulin and glucagon levels and less repeated treatments in dual-hormone AID. PG and glucagon levels at T0min were positively associated with increase in PG at T15min and negatively associated with time to recovery. ConclusionsNS-H self-management CHO 15-g/15-minute guidelines were neither excessive nor optimal during AID. There is a need to examine data with different AID systems to optimize treatment recommendations.

Pen-administered low-dose dasiglucagon vs usual care for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions: a Phase II, randomised, open-label, two-period crossover trial

Aims/hypothesisConsumption of excess carbohydrates to manage hypoglycaemia can lead to rebound hyperglycaemia and promote weight gain. The objective of this trial was to evaluate the efficacy, safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions.MethodsTwenty-four adults with insulin pump-treated type 1 diabetes (HbA1c ≤70 mmol/mol [8.5%]) completed a randomised, open-label, two-period crossover study with 2 week periods. During the usual care and dasiglucagon intervention (DASI) periods, participants managed impending and manifested episodes of hypoglycaemia with regular carbohydrate consumption or pen-administered low-dose (80 μg) s.c. dasiglucagon, respectively. Glycaemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event registration of prevention and treatment episodes.ResultsCompared with usual care, the mean difference (95% CI) in the DASI period for time in (3.9–10.0 mmol/l) and below (<3.9 mmol/l) range was 2.4 %-points (−0.7, 5.5) and −0.5 %-points (−1.2, 0.2), respectively. In the DASI period, recovery rate (time from hypoglycaemia treatment to euglycaemia) was 44% (11, 87) faster while total daily carbohydrate intake was reduced by 11% (−18, −3). Dasiglucagon use was safe and well tolerated with mild nausea being the most frequent adverse effect. Among the participants, 96% (p<0.0001) were likely to include dasiglucagon in their future routine management of hypoglycaemia.Conclusions/interpretationUse of low-dose dasiglucagon to prevent and treat non-severe hypoglycaemia during free-living conditions was safe, fast and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction.Trial registrationClinicalTrials.gov NCT04764968FundingThe study was an investigator-initiated trial. Zealand Pharma supplied the investigational drug and device and provided financial support for the conduct of the trial.Graphical abstract

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities

GPR40 AgoPAMs are highly effective antidiabetic agents that have a dual mechanism of action, stimulating both glucose-dependent insulin and GLP-1 secretion. The early lipophilic, aromatic pyrrolidine and dihydropyrazole GPR40 AgoPAMs from our laboratory were highly efficacious in lowering plasma glucose levels in rodents but possessed off-target activities and triggered rebound hyperglycemia in rats at high doses. A focus on increasing molecular complexity through saturation and chirality in combination with reducing polarity for the pyrrolidine AgoPAM chemotype resulted in the discovery of compound 46, which shows significantly reduced off-target activities as well as improved aqueous solubility, rapid absorption, and linear PK. In vivo, compound 46 significantly lowers plasma glucose levels in rats during an oral glucose challenge yet does not demonstrate the reactive hyperglycemia effect at high doses that was observed with earlier GPR40 AgoPAMs.

Hypoglycaemia and rebound hyperglycaemia increase left ventricular systolic function in patients with type 1 diabetes.

To investigate echocardiographic changes during acute hypoglycaemia followed by recovery to hyperglycaemia or euglycaemia in patients with type 1 diabetes. In a randomized crossover study, 24 patients with type 1 diabetes took part in two experimental study days, consisting of a hyperinsulinaemic-euglycaemic phase (5.0-8.0 mmol/L) for 45 minutes followed by a hyperinsulinemic-hypoglycaemic phase (2.5 mmol/L) for 60 minutes, and a recovery phase in either hyperglycaemia (20 mmol/L) or euglycaemia (5.0-8.0 mmol/L) for 60 minutes. Cardiac function was evaluated with echocardiography during each phase. Acute hypoglycaemia increased all markers of left ventricular (LV) systolic function, including LV ejection fraction (LVEF), global longitudinal strain (GLS), GLS rate and peak systolic velocity of mitral annular longitudinal movement (s'; P < 0.001 for all). During the recovery phases, all markers of LV systolic function were increased during hyperglycaemia (P < 0.01 for all), and LVEF and GLS remained increased during euglycaemia (P=0.0116 and P=0.0092, respectively). The increment in LVEF during the recovery phase was greater during hyperglycaemia than euglycaemia (P=0.0046). Hypoglycaemia, recent hypoglycaemia, and overcorrection of hypoglycaemia to rebound hyperglycaemia increased LV systolic function in type 1 diabetes and may imply consideration of plasma glucose when evaluating LV function in patients with type 1 diabetes. An increase in LV systolic function may cause increased strain on the heart and partly explain the link between hypoglycaemia, high glycaemic variability and cardiovascular disease.

Understanding Hypoglycemia in the Real World.

The purpose of this study was to gain a better understanding of real-world hypoglycemia experiences from people living with diabetes. An exploratory cross-sectional study of a convenience sample of 374 English-speaking adults affected by diabetes using an online survey was conducted. Participant mean age was 37 years with an average diabetes duration of 21 years. On average, participants reported feeling hypoglycemia at 64 mg/dL (3.6 mmol/L), worrying about hypoglycemia at 63 mg/dL (3.5 mmol/L), and treating hypoglycemia at 72 mg/dL (4 mmol/L). Terminology used by study participants did not match the current classifications of hypoglycemia used in clinical research. Participants who have been told they have hypoglycemia unawareness treat at a significantly lower level compared to those without hypoglycemia unawareness. Only 58% always carry hypoglycemia treatment; there was a relationship with increasing age and always carrying hypoglycemia treatment. Thirty-eight percent of participants treat hypoglycemia with the recommended 15 g of carbohydrate (CHO). Survey respondents who wore continuous glucose monitors reported using significantly less CHO to treat hypoglycemia. In the real world, experiences related to feeling, worrying about, and treating hypoglycemia trend higher than what is noted in the standardized hypoglycemia classifications. Study findings have implications for teaching and supporting people with diabetes who experience hypoglycemia. Consuming less CHO to treat hypoglycemia could lead to fewer episodes of rebound hyperglycemia and less weight gain. Increased support for continuous glucose monitoring is warranted.

Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients.

BackgroundNo consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia.MethodsPatients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108).ResultsThe rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups.ConclusionEarly co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Perioperative Management of a Rare Pancreatic Insulinoma Resection: Anaesthetic Challenge!

Insulinoma is a rare, mostly benign and solitary neuroendocrine tumour of the β-cells of islets of langerhans of pancreas. Clinically it presents with a classical ‘Whipple Triad’ encompassing symptomatic hypoglycemia, fasting hypoglycemia (&lt;50 mg/dl) and immediate relief of symptoms after glucose administration. Definitive treatment is laparoscopic or open surgical excision of the tumour. We report and discuss the distinctive anaesthetic considerations and implications during perioperative period. A comprehensive approach including preoperative optimization of blood glucose levels with various drugs and dietary modifications, scrupulous hemodynamic and blood sugar monitoring with prompt initiation of dextrose infusion during surgical handling of tumour and meticulous management of rebound hyperglycemia with insulin infusion in postoperative period remains the essence for better outcome in these subset of patients.

Weight-Based Insulin During and After Intravenous Insulin Infusion Reduces Rates of Rebound Hyperglycemia When Transitioning to Subcutaneous Insulin in the Medical Intensive Care Unit

ObjectiveHyperglycemia often occurs after the transition from intravenous insulin infusion (IVII) to subcutaneous insulin. Weight-based basal insulin initiated earlier in the course of IVII in the medical intensive care unit (MICU), and a weight-based basal-bolus regimen after IVII, can potentially improve post-IVII glycemic control by 48 hours. MethodsThis prospective study included 69 patients in MICU who were on IVII for ≥24 hours. Exclusions were end-stage renal disease, type 1 diabetes mellitus, and the active use of vasopressors. The intervention group received weight-based basal insulin (0.2-0.25 units/kg) with IVII and weight-based bolus insulin after IVII. The control group received current care. The primary end points were glucose levels at specific time intervals up to 48 hours after IVII. ResultsThere were 25 patients in the intervention group and 44 in the control group. The mean age of the patients was 59 ± 15 years, 32 (47%) were men, and 52 (78%) had prior diabetes mellitus. The 2 groups were not different (acute kidney injury/chronic kidney disease, pre-existing diabetes mellitus, illness severity, or nothing by mouth status after IVII), except for the steroid use, which was higher in the control group than in the intervention group (34% vs 12%, respectively). Glucose levels were not lower until 36 to 48 hours after IVII (166.8 ± 39.1 mg/dL vs 220.0 ± 82.9 mg/dL, P < .001). When controlling for body mass index, nutritional status, hemoglobin A1C, and steroid use, glucose level was lower starting at 12 to 24 hours out (166.87 mg/dL vs 207.50 mg/dL, P = .015). The frequency of hypoglycemia was similar between the 2 groups (5.0% vs 7.1%). The study did not reach target enrollment. ConclusionThe addition of weight-based basal insulin during, and basal-bolus insulin immediately after, IVII in MICU results in better glycemic control at 24 hours after IVII with no increased hypoglycemia.

ALL SUGARS ARE NOT SWEET

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Extravasation of vesicants occurs when there is leakage from a vessel into the surrounding area, with the potential to cause tissue necrosis. Common vesicants include vasopressors, alkylating chemotherapeutic agents, hyper-osmolar or hypo-osmolar agents, and certain antibiotics (vancomycin). Dextrose, at concentrations greater than 10% (D10), is also considered a vesicant, with rates of extravasation from 50% dextrose (D50) varying between 10-30% (1). CASE PRESENTATION: A cachectic 48-year-old with a history of HIV and alcohol and IV drug use, presented with lethargy. Upon initial assessment, she had track marks on her arms and was only responsive to sternal rub, with her exam otherwise unremarkable. She briefly improved with intravenous naloxone but ultimately required intensive care unit admission following intubation for airway protection. The toxicology screen was positive for methadone, opioids, and alcohol. Initial labs revealed ALT of 118 units/L, AST of 94 units/L, hemoglobin of 9.5 g/dL, and albumin of 2.3 g/dL. She was started on thiamine, multivitamin, and folate supplements. Despite starting tube feeds, fingerstick (FS) glucose was consistently low, dropping to 35 mg/dL. She received 2 ampules of 50 mL (25 g) 50% dextrose through a 22-gauge antecubital peripheral IV line, with FS improving to 220 mg/dL after 10 minutes. Two hours later, extensive swelling and fluid-filled blisters were noted throughout the forearm and hand, with Doppler ultrasound revealing the absence of a radial pulse. Her arm was elevated, a cold compress was applied, and a local subcutaneous injection of hyaluronidase was administered. Compartment pressures remained within normal limits, and a repeat Doppler ultrasound after an hour showed reappearance of a right radial pulse. The patient's swelling and blisters improved over the next few days. DISCUSSION: To the best of our knowledge, there are only three published cases on D50 extravasation so far, where D50 was administered by initial paramedic responders, in the field, in an emergent setting (1,2,3). D10 has a similar median time to recovery and post-treatment Glasgow Coma Scale, but with a decreased risk of rebound hyperglycemia. In our case, as the hypoglycemia incident occurred in an intensive care unit, administering D10 would have been a better option, as frequent FS monitoring would have been possible to assess response. Fortunately, close monitoring allowed for early recognition, prompt treatment, and good outcome. CONCLUSIONS: Hypoglycemia is a frequently encountered complication in a critical care setting. This case emphasizes the importance of early detection and treatment when suspecting extravasation of D50 to prevent the development of serious complications. D10 is now emerging as a safer and equally effective alternative to D50 and could become the standard of care for hypoglycemia management. REFERENCE #1: Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med. 2010 Feb;28(2):257.e1-2. doi: 10.1016/j.ajem.2009.06.010. PMID: 20159411. REFERENCE #2: Chinn M, Colella MR. Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report. Prehosp Emerg Care. 2017 Jan-Feb;21(1):79-82. doi: 10.1080/10903127.2016.1209263. Epub 2016 Sep 6. PMID: 27598324. REFERENCE #3: Lawson SL, Brady W, Mahmoud A. Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment--a clinical report. Am J Emerg Med. 2013 May;31(5):886.e3-5. doi: 10.1016/j.ajem.2012.12.010. Epub 2013 Apr 18. PMID: 23602753. DISCLOSURES: No relevant relationships by Natasha Garg, source=Web Response No relevant relationships by Archana Pattupara, source=Web Response No relevant relationships by Adam Rothman, source=Web Response No relevant relationships by DISHANT SHAH, source=Web Response