Inpatient Perioperative Euglycemic Diabetic Ketoacidosis Due to Sodium-Glucose Cotransporter-2 Inhibitors - Lessons From a Case Series and Strategies to Decrease Incidence.

OBJECTIVE: To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events. METHODS: Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA. RESULTS: A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively. CONCLUSION: Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.

Patient-Centered Diabetes Care of Cancer Patients.

PURPOSE OF REVIEW: There is a bidirectional relationship between cancer and diabetes, with one condition influencing the prognosis of the other. Multiple cancer therapies cause diabetes including well-established medications such as glucocorticoids and novel cancer therapies such as immune checkpoint inhibitors (CPIs) and phosphoinositide 3-kinase (PI3K) inhibitors. RECENT FINDINGS: The nature and severity of diabetes caused by each therapy differ, with some predominantly mediated by insulin resistance, such as PI3K inhibitors and glucocorticoids, while others by insulin deficiency, such as CPIs. Studies have demonstrated diabetes from CPIs to be more rapidly progressing than conventional type 1 diabetes. There remains a scarcity of published guidance for the screening, diagnosis, and management of hyperglycemia and diabetes from these therapies. The need for such guidance is critical because diabetes management in the cancer patient is complex, individualized, and requires inter-disciplinary care. In the present narrative review, we synthesize and summarize the most relevant literature pertaining to diabetes and hyperglycemia in the setting of these cancer therapies and provide an updated patient-centered framework for their evaluation and management.

Randomized Controlled Trials of Electronic Health Record Interventions: Design, Conduct, and Reporting Considerations.

Electronic health record (EHR) systems can be configured to deliver novel EHR interventions that influence clinical decision making and to support efficient randomized controlled trials (RCTs) designed to evaluate the effectiveness, safety, and costs of those interventions. In designing RCTs of EHR interventions, one should carefully consider the unit of randomization (for example, patient, encounter, clinician, or clinical unit), balancing concerns about contamination of an intervention across randomization units within clusters (for example, patients within clinical units) against the superior control of measured and unmeasured confounders that comes with randomizing a larger number of units. One should also consider whether the key computational assessment components of the EHR intervention, such as a predictive algorithm used to target a subgroup for decision support, should occur before randomization (so that only 1 subgroup is randomized) or after randomization (including all subgroups). When these components are applied after randomization, one must consider expected heterogeneity in the effect of the differential decision support across subgroups, which has implications for overall impact potential, analytic approach, and sample size planning. Trials of EHR interventions should be reviewed by an institutional review board, but may not require patient-level informed consent when the interventions being tested can be considered minimal risk or quality improvement, and when clinical decision making is supported, rather than controlled, by an EHR intervention. Data and safety monitoring for RCTs of EHR interventions should be conducted to guide institutional pragmatic decision making about implementation and ensure that continuing randomization remains justified. Reporting should follow the CONSORT (Consolidated Standards of Reporting Trials) Statement, with extensions for pragmatic trials and cluster RCTs when applicable, and should include detailed materials to enhance reproducibility.

Identifying Potential Intervention Points for Acute Hypoglycemic Events in Patients With Type 2 Diabetes Using Retrospective Clinical Data.

This retrospective study examined changes in medication orders as a risk factor for future acute hypoglycemic events. The investigators identified factors associated with acute hypoglycemic events resulting in emergency department visits or inpatient admissions. Non-Hispanic Black race, chronic kidney disease, insulin at baseline, and nonprivate insurance were associated with higher risk of an acute hypoglycemic event, whereas age, sex, and A1C were not. After adjustment for other risk factors, changes in insulin orders after A1C measurement were associated with a 1.5 times higher risk of an acute hypoglycemia (adjusted hazard ratio 1.48, 95% CI 1.08-2.03). These results further understanding of risk factors and clinical processes relevant to predicting and preventing acute hypoglycemia.

Association Between a Virtual Glucose Management Service and Glycemic Control in Hospitalized Adult Patients: An Observational Study.

BACKGROUND: Inpatient hyperglycemia is common and is linked to adverse patient outcomes. New methods to improve glycemic control are needed. OBJECTIVE: To determine whether a virtual glucose management service (vGMS) is associated with improved inpatient glycemic control. DESIGN: Cross-sectional analyses of three 12-month periods (pre-vGMS, transition, and vGMS) between 1 June 2012 and 31 May 2015. SETTING: 3 University of California, San Francisco, hospitals. PATIENTS: All nonobstetric adult inpatients who underwent point-of-care glucose testing. INTERVENTION: Hospitalized adult patients with 2 or more glucose values of 12.5 mmol/L or greater (≥225 mg/dL) (hyperglycemic) and/or a glucose level less than 3.9 mmol/L (<70 mg/dL) (hypoglycemic) in the previous 24 hours were identified using a daily glucose report. Based on review of the insulin/glucose chart in the electronic medical record, recommendations for insulin changes were entered in a vGMS note, which could be seen by all clinicians. MEASUREMENTS: Proportion of patient-days classified as hyperglycemic, hypoglycemic, and at-goal (all measurements ≥3.9 and ≤10 mmol/L [≥70 and ≤180 mg/dL] during the pre-vGMS, transition, and vGMS periods). RESULTS: The proportion of hyperglycemic patients decreased by 39%, from 6.6 per 100 patient-days in the pre-vGMS period to 4.0 per 100 patient-days in the vGMS period (difference, -2.5 [95% CI, -2.7 to -2.4]). The hypoglycemic proportion in the vGMS period was 36% lower than in the pre-vGMS period (difference, -0.28 [CI, -0.35 to -0.22]). Forty severe hypoglycemic events (<2.2 mmol/L [<40 mg/dL]) occurred during the pre-vGMS period compared with 15 during the vGMS period. LIMITATION: Information was not collected on patients' concurrent illnesses and treatment or physicians' responses to the vGMS notes. CONCLUSION: Implementation of the vGMS was associated with decreases in hyperglycemia and hypoglycemia. PRIMARY FUNDING SOURCE: National Institutes of Health, the Wilsey Family Foundation, and the UCSF Clinical & Translational Science Institute.

Remote Monitoring and Consultation of Inpatient Populations with Diabetes.

PURPOSE OF REVIEW: Inpatient hyperglycemia is common and is linked to increased morbidity and mortality. We review current and innovative ways diabetes specialists consult in the management of inpatient diabetes. RECENT FINDINGS: With electronic medical records (EMRs), remote monitoring and intervention may improve the management of inpatient hyperglycemia. Automated reports allow monitoring of glucose levels and allow diabetes teams to intervene through formal or remote consultation. Following a 2-year transition of our complex paper-based insulin order sets to be EMR based, we leveraged this change by developing new daily glycemic reports and a virtual glucose management service (vGMS). Based on a daily report identifying patients with two or more glucoses over 225 mg/dl and/or a glucose <70 mg/dl in the past 24 h, a vGMS note with management recommendations was placed in the chart. Following the introduction of the vGMS, the proportion of hyperglycemic patients decreased 39% from a baseline of 6.5 per 100 patient-days to 4.0 per 100 patient-days The hypoglycemia proportion decreased by 36%. Ninety-nine percent of surveyed medical and surgical residents said the vGMS was both important and helpful.

Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".

OBJECTIVES: We present the case of a 66-year-old woman who developed hypoglycemia following the prolonged infiltration of a high dose continuous peripheral IV insulin infusion. STUDY SELECTION: Case report. DATA SOURCES AND EXTRACTION: PubMed was searched for relevant literature on exogenous hyperinsulinemic hypoglycemia. DATA SYNTHESIS: The patient was postlung transplantation and was receiving high doses of glucocorticoids. Despite increasing the peripheral IV insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion line infiltrated, resulting in a large subcutaneous insulin depot, estimated to be 450 units of regular insulin. She subsequently experienced prolonged hypoglycemia that was managed with concentrated dextrose containing fluids. In our literature search, there were no similar case reports. The literature on insulin overdose, usually from suicide attempts, can help guide the management of iatrogenic hyperinsulinemic hypoglycemia. Important management considerations include anticipated duration of hypoglycemia, supplemental glucose, fluid management, and electrolyte monitoring. CONCLUSION: Peripheral IV insulin infusion infiltration should be considered when patients do not respond to increasing rates of insulin infusion.

Effect of moderately intense perioperative glucose control on renal allograft function: a pilot randomized controlled trial in renal transplantation.

Recipient diabetes accounts for ~34% of end-stage renal disease in patients awaiting renal transplantation and has been linked to poor graft function. We conducted a single-center, open-label, randomized controlled trial to determine whether moderately intense glucose control during allograft reperfusion would reduce the incidence of poor graft function. Adult diabetics undergoing deceased donor renal transplant were randomized to moderately intense glucose control (n=30) or standard control (n=30). The primary outcome was poor graft function (dialysis within seven days of transplant or failure of serum creatinine to fall by 10% for three consecutive days). Recipients with moderately intense glucose control had less poor graft function in the intention-to-treat (43.3% vs 73.3%, P=.02) and per-protocol analysis (43.2% vs 81%, P<.01). Recipients with moderately intense control also had higher glomerular filtration rate (GFR) at 30 days after transplant in the per-protocol and intention-to-treat analyses. There were no episodes of severe hypoglycemia in either group and no differences in mortality, seizures, stroke, graft loss, or biopsy-proven rejection. Moderately intense glucose control at the time of allograft reperfusion reduces the incidence of poor graft function in diabetic renal transplant recipients and improves glomerular filtration rate at 30 days.

Falsely Decreased HbA1c in a Type 2 Diabetic Patient Treated with Dapsone.

OBJECTIVE: To discuss a case of a falsely low hemoglobin A1c (HbA1c) in a transplant patient treated with dapsone and its implications. HbA1c is widely used as a measure of glycemic control in diabetic patients. With the increasing transplant population, it is important to be mindful of medications used in this population that can affect HbA1c and to use other measures of glycemic control to guide treatment decisions. METHODS: We present details of the case and review the relevant literature. RESULTS: A 61-year-old patient received a liver transplant in 2012 and subsequently was noted to have a falling HbA1c despite evidence of hyperglycemia based on fingerstick glucose and fructosamine measurements. Review of the medical records revealed that the discordance between HbA1c and fingerstick glucose levels developed after initiation of dapsone therapy. Dapsone may lead to a falsely low HbA1c via several mechanisms. Upon cessation of dapsone therapy, the patient's HbA1c returned to pre-dapsone levels. CONCLUSION: It is important to be aware of medications commonly used in transplant patients that may lead to a falsely low HbA1c level so that incorrect treatment decisions are not made. Fructosamine correlates with HbA1c and can be used as a measure of glycemic control in transplant patients when HbA1c cannot be used.

Outcomes and Adverse Events in Patients with Cancer after Diagnosis of Immunotherapy-Associated Diabetes Mellitus: A Retrospective Cohort Study.

Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher's exact tests, Student t-tests, Kaplan-Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM.

Novel Automated Self-adjusting Subcutaneous Insulin Algorithm Improves Glycemic Control and Physician Efficiency in Hospitalized Patients.

BACKGROUND: Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration. METHOD: We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified. RESULTS: The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing. CONCLUSIONS: The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place.

Discordant Timing of Hypoglycemic Agent Screening Causing Delayed Diagnosis of Sulfonylurea-Induced Hypoglycemia.

Background: Oral hypoglycemic agents are a frequent cause of hypoglycemia in nondiabetic people. Here, we report a case of recurrent hypoglycemia caused by glipizide, in which diagnosis was delayed because of a combination of delayed hypoglycemic agent screening and low sensitivity of the hypoglycemic agent screening panel used. Case Report: A 66-year-old woman repeatedly presented with symptomatic hypoglycemia. At the first presentation, the serum glucose level was 40 mg/dL (2.2 mmol/L), C-peptide level was 13.1 ng/mL (0.8-3.1 ng/mL), proinsulin level was 96.9 pmol/L (<18.8 pmol/L), and insulin level was 164 mU/L (<17 mU/L). An initial hypoglycemic agent screening, performed 24 hours after admission, yielded a negative result, leading to prolonged and recurrent hospitalizations for workup and localization of insulinoma. A hypoglycemic agent screening at a subsequent presentation, concordant with hypoglycemia, yielded a positive result for glipizide, which was at a level of 320 ng/mL (reporting limit, 40 ng/mL). An examination of the patient's home medications revealed a container, labeled as benztropine, containing glipizide tablets. After the diagnosis of glipizide-induced hypoglycemia, the patient had no further episodes of hypoglycemia. Discussion: The failure to detect glipizide using the initial hypoglycemia agent assay was likely because of a combination of a delay in the initial screening and low sensitivity of the assay for glipizide compared with that of other available assays. Here, we discuss important considerations for the interpretation of hypoglycemic agent screening in the diagnosis of hypoglycemia, including the timing of collection and reporting, pharmacokinetics of culprit agents, and sensitivity of the hypoglycemic agent panel used. Conclusion: Screening tests for hypoglycemic agents are necessary for the evaluation of hypoglycemia because their biochemical evaluation may be indistinguishable from that of insulinoma.

Management of Hyperglycemia in Hospitalized Adult Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Adult patients with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. These patients are at increased risk for adverse clinical outcomes in the absence of defined approaches to glycemic management. OBJECTIVE: To review and update the 2012 Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline and to address emerging areas specific to the target population of noncritically ill hospitalized patients with diabetes or newly recognized or stress-induced hyperglycemia. METHODS: A multidisciplinary panel of clinician experts, together with a patient representative and experts in systematic reviews and guideline development, identified and prioritized 10 clinical questions related to inpatient management of patients with diabetes and/or hyperglycemia. The systematic reviews queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. RESULTS: The panel agreed on 10 frequently encountered areas specific to glycemic management in the hospital for which 15 recommendations were made. The guideline includes conditional recommendations for hospital use of emerging diabetes technologies including continuous glucose monitoring and insulin pump therapy; insulin regimens for prandial insulin dosing, glucocorticoid, and enteral nutrition-associated hyperglycemia; and use of noninsulin therapies. Recommendations were also made for issues relating to preoperative glycemic measures, appropriate use of correctional insulin, and diabetes self-management education in the hospital. A conditional recommendation was made against preoperative use of caloric beverages in patients with diabetes. CONCLUSION: The recommendations are based on the consideration of important outcomes, practicality, feasibility, and patient values and preferences. These recommendations can be used to inform system improvement and clinical practice for this frequently encountered inpatient population.

Hospital Diabetes Meeting 2022.

The annual Virtual Hospital Diabetes Meeting was hosted by Diabetes Technology Society on April 1 and April 2, 2022. This meeting brought together experts in diabetes technology to discuss various new developments in the field of managing diabetes in hospitalized patients. Meeting topics included (1) digital health and the hospital, (2) blood glucose targets, (3) software for inpatient diabetes, (4) surgery, (5) transitions, (6) coronavirus disease and diabetes in the hospital, (7) drugs for diabetes, (8) continuous glucose monitoring, (9) quality improvement, (10) diabetes care and educatinon, and (11) uniting people, process, and technology to achieve optimal glycemic management. This meeting covered new technology that will enable better care of people with diabetes if they are hospitalized.