Iatrogenic Hypoglycemia Research Articles

The Use of a Single Risk Assessment Tool for Mortality and Numerous Hospital-Acquired Conditions.

Quality assessment organizations leverage numerous patient safety measures to evaluate hospital performance, resulting in significant financial, administrative, and operational burdens on health systems. Low-intensity approaches that allow for reliable risk stratification of patients can reduce the required investment. The Braden score is a routinely performed bedside nursing evaluation validated to assess risk for hospital-acquired pressure injury. We hypothesized that the tool can be used to evaluate risk for other hospital-related adverse outcomes, including mortality, catheter-associated urinary tract infection (CAUTI), and central line-associated blood stream infection (CLABSI). We found that abnormal Braden scores have significant association with numerous adverse outcome measures, including mortality, CLABSI, CAUTI, and iatrogenic hypoglycemia. Because of its frequency of reevaluation, we have found preliminary evidence that leveraging this tool can reduce harm by quickly identifying the most at-risk patients for various types of iatrogenic harm. We conclude that in the face of increasing automation and technical applications, for example, artificial intelligence-driven tools, highly reliable clinician bedside physical examination and evaluation can still have significant, low-cost, and high-value impact in improving patient safety.

Aging In The Face of Diabetes: Severe Hypoglycemia in Older Adults

Global rates of type 1 and type 2 diabetes (T1D, T2D) continue to climb, despite medical advancements. Older adults constitute one of the fastest growing segments of the diabetes population, backed by the world’s unprecedented aging population, decreased diabetes mortality rates, and the obesity epidemic. In Canada, individuals aged ≥65 years account for more than a quarter of all prevalent diabetes cases, far exceeding the other age groups. Older adults with diabetes face the highest risks of microvascular and macrovascular complications, which, compared to younger age cohorts, can contribute to significant functional loss, frailty, and premature mortality. A considerable amount of research links intensive glucose-lowering with insulin or secretagogues to reduced cardiovascular disease. However, the consequent risk of severe hypoglycemia and related sequelae can be particularly catastrophic for older adults, exacerbated by coexisting health conditions and age-related social needs. Approximately 40% of Canadians with T2D aged ≥65 years currently use secretagogues, while 27% use insulin—alongside all those with T1D. Longitudinal evidence suggests that since the year 2000, hospital admission rates for hypoglycemia have consistently surpassed those for hyperglycemia, especially among individuals aged 75 years and above. Economic modelling estimates that the Canadian healthcare system spends $125,932 CAD per year on iatrogenic hypoglycemia, with the bulk of these costs likely allocated to people ≥65 years. Diabetes in older adults is a pressing public health issue in Canada, marked by clinical diversity and widespread use of medications that are prone to cause hypoglycemia. This review outlines recent epidemiologic findings on severe hypoglycemia among community-dwelling older adults with T1D or T2D treated with insulin or secretagogues. Understanding the complex factors contributing to severe hypoglycemia in this population is crucial for developing tailored prevention strategies that are both effective and safe.

Medical database analysis of the association between kidney function and achievement of glycemic control in older Japanese adults with type 2 diabetes who started with oral antidiabetic drugs.

Despite the emergence of new drugs with novel mechanisms of action, treatment options for older people and those with chronic kidney disease are still limited. Using a medical database compiled from Diagnostic Procedure Combination hospitals, we retrospectively analyzed treatment status, glycemic control and kidney function over 3 years after the first oral antidiabetic drugs in Japanese adults with type 2 diabetes who were aged ≥65 years. Among 5,434 study participants, 3,246 (59.7%) were men, the median age was 72.0 years, the baseline median hemoglobin A1c was 7.1% and the baseline median estimated glomerular filtration rate was 66.6 mL/min/1.73 m2. Treatment was intensified in 40.0% of people during the 3-year observation period, and the median time to the first treatment intensification was 198 days. Insulin was the most commonly used agent for treatment intensification (36.9%, 802/2,175). Hemoglobin A1c of <7.0% was achieved in 3,571 (65.7%) at 360 ± 90 days. Multivariable logistic regression analysis found that baseline age, hemoglobin A1c and estimated glomerular filtration rate were negatively associated with achieving hemoglobin A1c of <7.0% at 360 ± 90 days. In older Japanese adults with type 2 diabetes, those with a lower estimated glomerular filtration rate were more likely to achieve hemoglobin A1c of <7.0%. To safely manage blood glucose levels in older adults with chronic kidney disease, physicians should remain vigilant about the risk of iatrogenic hypoglycemia.

Reducing the harm associated in treating hyperkalaemia with insulin and dextrose

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04).

Vulnerable Hours of the Day for Severe Iatrogenic Hypoglycaemia in Type 2 Diabetes: A Single-Centre Retrospective Study.

Iatrogenic hypoglycaemia is an event that should be avoided in the treatment of diabetes, but the pathophysiology thereof has been poorly examined and reported. There is no established method for preventing iatrogenic hypoglycaemia and the current approach is a reactive response following onset of the disease. In this study, we aimed to explore the existence of 'hypoglycaemia-vulnerable hours of the day' in patients with type 2 diabetes, with the ultimate goal of preventing the onset of iatrogenic hypoglycaemia by clarifying the time when severe hypoglycaemia is likely to occur. Of the 553,201 patients who visited the Critical Care and Emergency Center of Aizawa Hospital between 2008 and 2019, patients with proven hypoglycaemia (blood glucose level <3.0 mmol/L) and those using insulin or oral hypoglycaemic agents for the treatment of type 2 diabetes were included: 146 insulin users and 148 oral hypoglycaemic agent users. Cosinor analysis was employed to identify hypoglycaemia-vulnerable hours of the day. Patients with type 2 diabetes and severe hypoglycaemia had two peaks: at 8:00 and 18:00-19:00. Hypoglycaemia was observed as quadra-peaked in insulin users and double-peaked in oral hypoglycaemic agent users. Single-cosinor analysis revealed that the cycle was 5.83 hours (R=0.417) in insulin users, whereas it was 11.0 hours (R=0.717) in oral hypoglycaemic agent users. In insulin users, a significant periodicity of sixhours (P=0.003) was observed in the cosinor detection analysis, and a significant correlation (P<0.05) was present in the cosinor percent rhythmicity analysis. In contrast, in oral hypoglycaemic agent users, a significant periodicity of 11 hours (P=0.03) was ascertained in the cosinor detection analysis, and there was a significant correlation (P<0.001) in the cosinor percent rhythmicity analysis. There were different hypoglycaemia-vulnerable hours of the day in the patients with type 2 diabetes, suggesting an interaction between disease pathophysiology and pharmacology. These results can help elucidate the trend of the development of iatrogenic hypoglycaemia and contribute to the prevention of the onset thereof.

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.

Noniatrogenic hypoglycemia: A universal marker for poor outcomes

ObjectivePrevious retrospective studies have established a relationship between postoperative hypoglycemia and adverse outcomes after cardiac surgery, but none have accounted for the cause of hypoglycemia. MethodsA retrospective review was performed of patients who underwent cardiac surgery at a single institution between 2016 and 2021. Patients were categorized as hypoglycemic if they had 1 or more postoperative blood glucose measurement less than 70 mg/dL and normoglycemic otherwise. Hypoglycemia was subcategorized as noniatrogenic (underlying liver failure, adrenal insufficiency, sepsis, or shock) or iatrogenic (insulin infusion continued while nil per os or infusion protocol violated) via manual chart review. Baseline characteristics were compared between groups using Pearson χ2, analysis of variance, and Kruskal-Wallis testing, and outcomes were compared using multivariable logistic regression. ResultsIn total, 5373 patients and 183,346 glucose measurements were included. Hypoglycemia occurred in 5% (267) of patients, of whom 63% (169) were iatrogenic and 37% (98) were noniatrogenic. In a multivariate analysis adjusting for age, sex, case urgency, pre-existing diabetes, and bypass time, both iatrogenic and noniatrogenic hypoglycemia were associated with greater odds of renal failure, prolonged ventilation, and prolonged intensive care unit length of stay relative to normoglycemia, but the magnitude was substantially lower in iatrogenic hypoglycemia. Patients with noniatrogenic hypoglycemia had 68.6 times greater odds of mortality relative to patients who were normoglycemic (odds ratio, 68.6; confidence interval, 39.5-119), but patients with iatrogenic hypoglycemia had no increased odds of mortality (odds ratio, 1.45; confidence interval, 0.77-2.73). ConclusionsWhen excluding patients with conditions known to cause hypoglycemia from the analysis, the morbidity and mortality of iatrogenic hypoglycemia from tight postoperative glycemic control is dramatically attenuated.

A potential role for GPR107 in the development of Hypoglycemia Unawareness

Diabetes remains one of the largest health burdens in modern society and while an estimated 37.3 million people suffer from either type 1 or type 2 diabetes worldwide, a further 96 million people are currently estimated to be prediabetic. So far, most efforts for diabetic therapies have been focused on insulin-replacement therapies and secretagogues; however, a common risk associated with these therapies is hypoglycemia. Hypoglycemia is defined as low plasma glucose levels (&lt; 70 mg/dl) and can lead to loss of consciousness and death. Recently, it has been established that repeated exposure to bouts of hypoglycemia in diabetic individuals likely impairs sympathoadrenal counter regulation, and shifts the glycemic threshold for symptoms to lower plasma glucose concentrations, close to levels which result in cognitive failure. This pathology has been titled hypoglycemia unawareness (HU) and constitutes a major risk factor for developing severe hypoglycemia. The development of severe hypoglycemia in diabetics accounts for a six-fold increase in mortality, compared to diabetic individuals who do not experience severe hypoglycemia. Thus, it is important to understand how to prevent and reverse its development. We have developed a novel rat model of HU in which rats are exposed to insulin-induced recurrent hypoglycemia for five consecutive days. In this model of HU, we found that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Our group previously identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone, which can exert anorexigenic actions in the hypothalamus. Using a GPR107-flox rat model we are currently evaluating the effect of hypothalamic knock-down of GPR107 on the development of HU and basal feeding behavior. We anticipate that if knock-down of GPR107 reverses HU, the development of NST antagonists could potentially be useful therapeutically for diabetic patients who experience recurrent hypoglycemia. Our GPR107-flox rat model will enable us to identify upstream and downstream interacting partners of GPR107/NST. This could reveal hypothalamic pathways involved in the development of HU that also could serve as potential therapeutic targets for this devastation consequence of iatrogenic hypoglycemia. Internal Funds St. Louis University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Re-audit of the Management of Diabetic Ketoacidosis (DKA): The Importance of the Seven-Day Working Inpatient Diabetes Specialist Nurse Service.

Background Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency due to insulin deficiency in patients with diabetes mellitus. The United Kingdom national survey and local audits of the management of DKA have revealed several areas of suboptimal care, and room for improvement, necessitating the need for intensified education, updating local guidelines, and increased recruitment of seven-day working inpatient diabetes specialist nurses. Therefore, this project aimed to re-audit our adherence to the DKA treatment guidelines. Methodology A retrospective re-audit examining patient admissions with DKA between October 2022 and September 2023. A list of 18 standards/criteria, adopted from the Joint British Diabetes Society (JBDS) DKA treatment guidelines was used for this re-audit. Results were compared with that of the previous audit. Results We had 126 patients admitted with DKA between October 2022 and September 2023. There were 62 males and 64 females with an average (range) age of 46.5 (19-92) years. Eighty percent had type 1 diabetes, and common precipitating factors for admission included infection and poor adherence to insulin treatment. The median (IQR) length of hospital stay was 2.1 (1.0-5.1) days. Compared to the previous audit, improvements occurred in 11 of 18 standards/criteria. This included timely commencement of intravenous fluids and fixed-rate insulin, commencing glucose infusion to prevent hypoglycemia,potassium replacement, continuation of long-acting insulin during treatment, timely conversion to variable-rate insulin infusion, and conversion to the usual subcutaneous insulin regimen. Additionally, 124 patients (98.4%) were reviewed at least once by the inpatient diabetes specialist nurses (DSN) during their admission. Complications of treatment, namely, iatrogenic hypoglycemia and transient hypokalemia occurred in 13 (10.3%) and 40 (31.7%) patient admissions, respectively. Conclusions This re-audit demonstrated improved adherence to the guidelines during several steps in the management of DKA. It also demonstrated room for improvement regarding other aspects of care. The importance of continued education, accurate documentation, and the presence of seven-day working inpatient DSN cover cannot be overemphasized.

Euglycemic Diabetic Ketoacidosis: Experience with 44 Patients and Comparison to Hyperglycemic Diabetic Ketoacidosis.

Euglycemic diabetic ketoacidosis (DKA) (glucose <250milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2 (SGLT2) inhibitors but remains challenging to diagnose and manage without the hyperglycemia that is otherwise central to diagnosing DKA, and with increased risk for hypoglycemia with insulin use. Our objective was to compare key resource utilization and safety outcomes between patients with euglycemic and hyperglycemic DKA from the same period. This is a retrospective review of adult emergency department patients in DKA at an academic medical center. Patients were included if they were >18years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (<250milligrams per deciliter [mg/dL]) vs hyperglycemic (≥250mg/dL) cohorts by presenting glucose. We extracted and analyzed patient demographics, resource utilization, and safety outcomes. Etiologies of euglycemia were obtained by manual chart review. For comparisons between groups we used independent-group t-tests for continuous variables and chi-squared tests for binary variables, with alpha 0.05. We identified 629 patients with DKA: 44 euglycemic and 585 hyperglycemic. Euglycemic patients had milder DKA on presentation (higher pH and bicarbonate, lower anion gap; P < 0.05) and lower initial glucose (195 vs 561mg/dL, P < 0.001) and potassium (4.3 vs 5.3mmol/L, P < 0.001). Etiologies of euglycemia were insulin use prior to arrival (57%), poor oral intake with baseline insulin use (29%), and SGLT2 inhibitor use (14%). Mean time on insulin infusion was shorter for those with euglycemic DKA: 13.5 vs 19.4 hours, P = 0.003. Mean times to first bicarbonate >18mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (<70mg/dL) while on insulin infusion was significantly higher for those with euglycemic DKA (18.2 vs 4.8%, P = 0.02); incidence of hypokalemia (<3.3mmol/L) was 27.3 vs 19.1% (P = 0.23). Compared to hyperglycemic DKA patients managed in the same protocolized fashion, euglycemic DKA patients were on insulin infusions 5.9 hours less, yet experienced hypoglycemia over three times more frequently. Future work can investigate treatment strategies for euglycemic DKA to minimize adverse events, especially iatrogenic hypoglycemia.

Serotonergic neurons are involved in the counter-regulatory response to hypoglycemia.

Intensive insulin therapy provides optimal glycemic control in patients with diabetes. However, intensive insulin therapy causes so-called iatrogenic hypoglycemia as a major adverse effect. The ventromedial hypothalamus (VMH) has been described as the primary brain area initiating the counter-regulatory response (CRR). Nevertheless, the VMH receives projections from other brain areas which could participate in the regulation of the CRR. In particular, studies suggest a potential role of the serotonin (5-HT) network. Thus, the objective of this study was to determine the contribution of 5-HT neurons in CRR control. Complementary approaches have been used to test this hypothesis in quantifying the level of 5-HT in several brain areas by HPLC in response to insulin-induced hypoglycemia, measuring the electrical activity of dorsal raphe (DR) 5-HT neurons in response to insulin or decreased glucose level by patch-clamp electrophysiology; and measuring the CRR hormone glucagon as an index of the CRR to the modulation of the activity of 5-HT neurons using pharmacological or pharmacogenetic approaches. HPLC measurements show that the 5HIAA/5HT ratio is increased in several brain regions including the VMH in response to insulin-induced hypoglycemia. Patch-clamp electrophysiological recordings show that insulin, but not decreased glucose level, increases the firing frequency of DR 5-HT neurons in the DR. In vivo, both the pharmacological inhibition of 5-HT neurons by intraperitoneal injection of the 5-HT1A receptor agonist 8-OH-DPAT or the chemogenetic inhibition of these neurons reduce glucagon secretion, suggesting an impaired CRR. Taken together, these data highlight a new neuronal network involved in the regulation of the CRR. In particular, this study shows that DR 5-HT neurons detect iatrogenic hypoglycemia in response to the increased insulin level and may play an important role in the regulation of CRR.

SAT138 “Zero”Ing On Hypoglycemia Caused By Hyperkalemia Treatments In The Inpatient Setting

Abstract Disclosure: S. Kim: None. H. Tran: None. R.Y. Gianchandani: None. Background: Severe hyperkalemia can be life-threatening, therefore, is urgently treated in the hospital with intravenous (IV) insulin. An insulin dose of 10 units given with dextrose is considered standard of care. Hypoglycemia associated with hyperkalemia treatment was identified as a significant contributing factor to our overall hypoglycemia rate in the hospital. We designed a hyperkalemia quality improvement (QI) project based on recent studies demonstrating improvement in hypoglycemia rates with weight-based insulin dosing, without clinically impacting potassium-lowering effects. Methods: 5 months of retrospective data was collected before and after implementing a revised hyperkalemia orderset. Prior to implementation, regular insulin was dosed at 10 units intravenously along with 25 g of 50 percent dextrose (D50W). In the updated orderset, regular insulin was dosed at 0.1 units/kg of body weight up to a maximum of 10 units with 25 g of D50W. Additionally, the revised orderset included options for ordering alternative hyperkalemia treatment modalities along with monitoring parameters. A point of care BG was ordered at one hour post treatment. A utilization report was generated for pre- and post-implementation when IV insulin was ordered from hyperkalemia orderset. Additionally, patients who received IV insulin independent of the orderset during the post-implementation period were evaluated. The primary endpoint is the rate of hypoglycemia (BG &amp;lt;70 mg/dL) within 6 hours of IV insulin and D50W administration for hyperkalemia treatment. Results: In the pre-implementation period, 604 doses of insulin were administered from the original orderset with a hypoglycemia rate of 9.8% at 6 hours. Post-implementation, 322 doses were administered from the revised orderset which had a hypoglycemia rate of 5% at 6 hours. Partial adoption of the revised hyperkalemia orderset resulted in 281 doses of insulin treatment ordered independent of the new orderset and hypoglycemia rates remained high at 9.6% at 6 hours in this group. Most of these were in the emergency room where there was low orderset adoption.95% (21/22) of patients who experienced hypoglycemia despite using weight-based insulin dosing for hyperkalemia treatment had an initial BG ≤150 mg/dL and 59.1% (13/22) had a CrCl &amp;lt;30 mL/min or ESRD. Conclusion: A QI process utilizing weight-based insulin dosing for the treatment hyperkalemia reduced hypoglycemia rates by half. Patients who continued to have low BG post intervention were those with a pretreatment BG ≤150 mg/dL. We further revised our orderset to utilize a higher dose of dextrose (D50W 50 g) if pretreatment BG was less than 150 mg/dL and will be implementing this shortly. Additionally, we will work with the emergency room to assist in their hyperkalemia management. With follow-up data, we plan to reach negligible rates of iatrogenic hypoglycemia with our hyperkalemia interventions. Presentation: Saturday, June 17, 2023

The Role of Glucose Concentration and Resveratrol in Modulating Neuroinflammatory Cytokines: Insights from an In Vitro Blood-Brain Barrier Model.

BACKGROUND The prevalence of type 2 diabetes mellitus is rising, presumably because of a coexisting pandemic of obesity. Since diabetic neuropathy and neuroinflammation are frequent and significant complications of both prolonged hyperglycemia and iatrogenic hypoglycemia, the effect of glucose concentration and resveratrol (RSV) supplementation on cytokine profile was assessed in an in vitro model of the blood-brain barrier (BBB). MATERIAL AND METHODS The in vitro model of BBB was formed of endothelial cells and astrocytes, which represented the microvascular and brain compartments (MC and BC, respectively). The BC concentrations of selected cytokines - IL-10, IL-12, IL-17A, TNF-alpha, IFN-γ, GM-CSF in response to different glucose concentrations in the MC were studied. The influence of LPS in the BC and RSV in the MC on the cytokine profile in the BC was examined. RESULTS Low glucose concentration (40 mg/dL) in the MC resulted in increased concentration of all the cytokines in the BC except TNF-alpha, compared to normoglycemia-imitating conditions (90 mg/dL) (P<0.05). High glucose concentration (450 mg/dL) in the MC elevated the concentration of all the cytokines in the BC (P<0.05). RSV decreased the level of all cytokines in the BC after 24 h following its administration for all glucose concentrations in the MC (P<0.02). The greatest decline was observed in normoglycemic conditions (P<0.05). CONCLUSIONS Both hypo- and hyperglycemia-simulating conditions impair the cytokine profile in BC, while RSV can normalize it, despite relatively poor penetration through the BBB. RSV exhibits anti-neuroinflammatory effects, especially in the group with normoglycemia-simulating conditions.

3-OR: Severe Hypoglycemia among Older Adults with Diabetes (iNPHORM, USA)

Despite an aging US diabetes population, little is known about the real-world frequency of iatrogenic severe hypoglycemia (SH) among older adults. We analyzed iNPHORM data to address this gap. People ≥60-year-old with T1DM or T2DM on insulin and/or secretagogues were recruited from a probability-based internet panel. Data on SH were obtained via a screener, baseline, and 12 monthly follow-ups. Crude SH incidence rates (IRs) and proportions (IPs) were calculated overall, and by diabetes type, medication type, and mode of SH recovery. N=307 were analyzed (T1DM: 8.5%; age: 67.5 [SD:5.5] years; male: 54.1%; retention rate: 81.8%). Among T2DM respondents, 39.9% used insulin without secretagogues, 50.2% secretagogues without insulin, and 10.0% insulin and secretagogues. The overall IP of SH was 19.9 (95%CI: 15.8-24.7)%, and the IR was 0.89 (95%CI: 0.62-1.27) events per person-year (EPPY). People with T1DM had a higher total IP (42.3 [95%CI: 25.5-61.1]%) and IR (2.07 [95%CI: 0.98-4.38] EPPY) than those with T2DM (IP: 17.8 [95%CI: 13.8-22.7]%; IR: 0.78 [95%CI: 0.52-1.15] EPPY), including insulin without secretagogue users (1.09 [95%CI: 0.66-1.80] vs. 0.61 [95%CI: 0.26 to 1.45] [insulin with secretagogues] and 0.50 [95%CI: 0.23 to 1.05] [secretagogues without insulin] EPPY). Emergency care and hospitalization constituted 3.6% (T1DM: 0%; T2DM: 6.7%) and 1.8% (T1DM: 0%; T2DM: 2.2%) of SH (n=224), respectively. Paramedical/hospital-based SH was more common in T2DM (0.06 [95%CI: 0.02-0.19]) than T1DM (0 EPPY) with IRs highest among insulin without secretagogue users (0.11 [95%CI: 0.03-0.47] EPPY). This is the first US prospective study on SH frequency in older adults with diabetes. Most (96.4%) events occurred at-home, underscoring the need for self-reported SH capture. Overall IPs and IRs were greater in T1DM than T2DM; but those with T2DM had more healthcare-based events. To mitigate undue health and economic costs, it is imperative clinicians remain vigilant to preventing SH in this vulnerable and growing population. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

Continuous Glucose Monitoring in the Intensive Care Unit.

Traditionally, the care of critically ill patients with diabetes or stress hyperglycemia in the intensive care unit (ICU) demands the use of continuous intravenous insulin (CII) therapy to achieve narrow glycemic targets. To reduce the risk of iatrogenic hypoglycemia and to achieve glycemic targets during CII, healthcare providers (HCP) rely on hourly point-of-care (POC) arterial or capillary glucose tests obtained with glucose monitors. The burden of this approach, however, was evident during the beginning of the pandemic when the immediate reduction in close contact interactions between HCP and patients with COVID-19 was necessary to avoid potentially life-threatening exposures. Taking advantage of the advancements in current diabetes technologies, including continuous glucose monitoring (CGM) devices integrated with digital health tools for remote monitoring, HCP implemented novel protocols in the ICU to care for patients with COVID-19 and hyperglycemia. We provide an overview of research conducted in the ICU setting with the use of initial CGM technology to current devices and summarize our recent experience in the ICU.

The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?

Replacement of β cells is only a curative approach for type 1 diabetes (T1D) patients to avoid the threat of iatrogenic hypoglycemia. In this pursuit, islet allotransplantation under Edmonton's protocol emerged as a medical miracle to attain hypoglycemia-free insulin independence in T1D. Shortage of allo-islet donors and post-transplantation (post-tx) islet loss are still unmet hurdles for the widespread application of this therapeutic regimen. The long-term survival and effective insulin independence in preclinical studies have strongly suggested pig islets to cure overt hyperglycemia. Importantly, CRISPR-Cas9 technology is pursuing to develop "humanized" pig islets that could overcome the lifelong immunosuppression drug regimen. Lately, induced pluripotent stem cell (iPSC)-derived β cell approaches are also gaining momentum and may hold promise to yield a significant supply of insulin-producing cells. Theoretically, personalized β cells derived from a patient's iPSCs is one exciting approach, but β cell-specific immunity in T1D recipients would still be a challenge. In this context, encapsulation studies on both pig islet as well as iPSC-β cells were found promising and rendered long-term survival in mice. Oxygen tension and blood vessel growth within the capsules are a few of the hurdles that need to be addressed. In conclusion, challenges associated with both procedures, xenotransplantation (of pig-derived islets) and stem cell transplantation, are required to be cautiously resolved before their clinical application.

Predicting Real-world Severe Hypoglycemia Risk in Diabetes (iNPHORM, USA)

In the United States (US), prognostic models for iatrogenic severe hypoglycemia (SH) derive from secondary sources subject to poor generalizability, data gaps and outcome ascertainment bias. Redressing this gap, we conducted the primary, longitudinal iNPHORM study.

PSUN272 Opportunity for Inpatient Use of Continuous Glucose Monitoring: A Case Report of Acute Pancreatitis Secondary to Hypertriglyceridemia

Abstract Background Continuous glucose monitoring (CGM) is a convenient method of estimating blood glucose (BG) levels through a minimally invasive subcutaneous electrode that senses interstitial fluid glucose readings. With recent advancements, this technology has the potential to transmit interstitial fluid glucose readings to electronic health records (EHR) in real-time. While some benefits of CGM have been studied in outpatient settings, current CGM research is beginning to explore the use and benefits of CGM in inpatient settings. The following case of acute pancreatitis (AP) secondary to hypertriglyceridemia (HTG) presents a novel opportunity for inpatient use of CGM. Clinical Case A 33-year-old-man with anxiety, alcohol use disorder, and without insulin resistance, presents as a transfer to a tertiary-care-center for consideration of plasmapheresis in the setting of AP secondary to HTG. He initially presented to outside hospital with acute onset diffuse abdominal pain. Family history of father with controlled HTG and hyperlipidemia on statins. Hemodynamically stable. Examination revealed diffuse abdominal tenderness. Labs revealed triglyceride (TG) level 3550 mg/dL (n&amp;lt;150 mg/dL), lipase 1423 U/L (n 0-160 U/L), TSH normal, A1c 5.2% (n&amp;lt;5.7%). CT abdomen pelvis with contrast revealed moderate acute interstitial edematous pancreatitis without necrosis, pseudocyst, or mass. He was volume resuscitated with intravenous (IV) fluids, then started on a non-titratable regular insulin infusion (N-TII) at 2 U/hr and continuous IV fluids with dextrose. Upon arrival, his BG was 101 mg/dL. The N-TII rate was decreased to 1 U/hr and managed with hourly finger-stick BG checks and continuous IV fluids with dextrose plus KCl. Arrival TG was 954 mg/dL. The case was discussed with Transfusion Medicine—given the down-trending TG level, plasmapheresis was not initiated. The next morning, repeat TG level was &amp;lt;500 mg/dL, thus, the N-TII was discontinued. During admission, BG ranged from 86-179 mg/dL and IV fluids with dextrose required titration of rate and concentration to avoid hypoglycemia while severe HTG resolved. Conclusion This case presents a novel scenario in which there is an opportunity for inpatient use of CGM. In addition to point-of-care finger-stick BG checks, the implementation of inpatient CGM may be beneficial in tracking glucose trends when N-TII are required for management of severe HTG, but risk iatrogenic hypoglycemia. Not only does this highlight an area in need of further research and technological developments that link CGM data to EHR in real-time, but also, by continuing to identify new opportunities for inpatient CGM use, we can better understand its nuances and implications, thus, thoughtfully advocate for policies and protocols that optimize benefits and justify cost of inpatient CGM. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Prevalence and characteristics of factitious hypoglycaemia in non-diabetic patients in a department of endocrinology.

Factitious hypoglycaemia is defined as the surreptitious use of insulin or oral hypoglycaemic agents to deliberately induce self-harm. It represents a challenging diagnosis and misdiagnosis is associated with significant morbidity and mortality. The aim of this study was to assess the prevalence and the associated factors of factitious hypoglycaemia in non-diabetic patients. This was a single-centre, retrospective study including 70 non-diabetic patients who were admitted for the investigation of hypoglycaemia. All patients fulfilled the Whipple triad. Epidemiological parameters, medical history, clinical and paraclinical data and the aetiology of hypoglycaemia were collected from medical records. The diagnosis of factitious hypoglycaemia was held in 11 patients (9 women and 2 men) corresponding to a prevalence of 16%. It was secondary to intentional insulin use in six patients and the ingestion of glibenclamide in five patients. The median age of the patients was 28 years (interquartile range: 21-43). Two patients with factitious hypoglycaemia had a personal history of psychiatric disorders. The other causes of hypoglycaemia were adrenal insufficiency (34%), prediabetes (24%), insulinoma (6%), iatrogenic hypoglycaemia (10%), criminal hypoglycaemia (1%) and alcohol intoxication (2%). Age ≤ 35 years (Odds Ratio=5.6, p=.017), family history of diabetes mellitus (Odds Ratio=1.29, p=.015), attention disorders during hypoglycaemia (Odds Ratio=12.5, p=.017) and fasting glucose level <0.7g/L (Odds Ratio=5.75, p=.017) were positively associated with factitious hypoglycaemia. Factors significantly associated with factitious hypoglycaemia were young age, family history of diabetes and a low fasting glucose level.

Dextrose-Containing Infusion Running in An Arterial Line System

Processes and procedures in intensive care units and during anaesthetic delivery are centered around ensuring patient safety. This article aims to shed light on a rare possible mechanism for inadvertent iatrogenic hypoglycaemia as can affect critical care specialists or anaesthetists in the line of service delivery and recommendations have been suggested.