Active use of Cocaine: An Independent Risk Factor for Recurrent Diabetic Ketoacidosis in a City Hospital

ObjectiveTo identify the risk factors for recurrent diabetic ketoacidosis (DKA) in a city hospital.MethodsWe performed a retrospective analysis of sequential adult admissions for DKA at Bronx Lebanon Hospital Center in New York between July 1, 2001, and June 30, 2004. The patients were divided into cohorts, which were compared with use of analysis of variance and χ² tests. Multivariate logistic regression analysis was performed where indicated.ResultsIn 168 patients (96 men and 72 women), 219 episodes of DKA occurred. The mean age (± SD) of the overall study group was 38.6 ± 14.8 years. Fifty-four patients (32%) had type 2 diabetes, and 44 patients (26%) had new-onset diabetes. The recurrence rate of DKA was 169% in cocaine users and 39% in nonusers (P < 0.0001). Active use of cocaine, noncompliance, and Hispanic ethnicity emerged as independent risk factors for recurrent DKA—odds ratio (OR) = 4.38, P = 0.001; OR = 1.96, P = 0.05; and OR = 0.40, P = 0.005, respectively. The commonest precipitants of DKA were noncompliance (44%) and infection (26%). Noncompliance was associated with use of cocaine, use of cannabis, and cigarette smoking (P = 0.008, 0.04, and 0.01, respectively). In 91 of the hospital admissions for DKA (42%), the patients were active smokers.ConclusionActive use of cocaine is an independent risk factor for recurrent DKA, as are noncompliance and Hispanic ethnicity. Of these 3 factors, cocaine showed the strongest association with DKA. Therefore, toxicology screening in patients with recurrent DKA may be prudent and worthwhile. (Endocr Pract. 2007;13:22-29)     

Diabetic Ketoacidosis in Peruvian Patients with Type 2 Diabetes Mellitus

ObjectiveTo describe the clinical and laboratory characteristics of diabetic ketoacidosis (DKA) in adult Peruvian patients with type 2 diabetes mellitus.MethodsIn this cross-sectional analysis, we reviewed clinical charts of type 2 diabetic patients with DKA admitted to Cayetano Heredia Hospital between 2001 and 2005 for data on demographics, previous treatment, previous hospital admissions for DKA, family history of diabetes, precipitating factors, hospital course, mortality, and insulin use 3 and 6 months after the index DKA episode. Patients older than 18 years who had confirmed DKA were included. Patients with type 1 diabetes mellitus were excluded.ResultsWe report on 53 patients with DKA for whom complete clinical and laboratory data were available. Of the 53 patients, 39 (74%) were men; mean age (± SD) was 45 ± 12 years; and 22 (42%) had no previous diagnosis of type 2 diabetes. The following mean (± SD) laboratory values were obtained at DKA diagnosis: glucose, 457 ± 170 mg/dL; pH, 7.15 ± 0.14; bicarbonate, 7.73 ± 6 mEq/L; and anion gap, 24.45 ± 7.44 mEq/L. Of the 53 DKA episodes, 35 (66%) were severe (arterial pH < 7.0 and/or serum bicarbonate < 10 mEq/L). The following precipitating factors were discerned: discontinuation of treatment in 21 (40%), infections in 16 (30%), intercurrent illness in 3 (6%), and no identifiable cause in 13 (25%). Mortality rate was 0%. Three and 6 months after the index DKA episode, insulin was used by 65% and 56% of patients, respectively.ConclusionIn countries with a low incidence of type 1 diabetes, DKA is frequently reported in patients with type 2 diabetes. In this study, 42% of patients had new-onset disease. Most DKA episodes were severe and were related to infection or noncompliance with treatment. (Endocr Pract. 2008;14:442-446)     

Family History of Diabetes is Associated with Increased Risk of Recurrent Diabetic Ketoacidosis in Pediatric Patients

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM).Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM.Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household.Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Recurrent diabetic ketoacidosis: causes, prevention and management

Longitudinal studies indicate that 20% of paediatric patients account for 80% of all admissions for diabetic ketoacidosis (DKA). The frequency of DKA peaks during adolescence and, although individuals generally go into remission, they may continue to have bouts of recurrent DKA in adulthood. The evidence for insulin omission being the behavioural precursor to recurrent DKA is reviewed and discussed. Thereafter the range of possible psychosocial causes is explored and the evidence for each discussed. Approaches to assessing the individual and their family to identify aetiology and therefore appropriate intervention are considered and treatment options reviewed. Finally, the paper examines potential risk factors for recurrent DKA, possible strategies for identifying these early and how to use these assessments to prevent subsequent recurrent DKA.     

Continuous Subcutaneous Infusion of Insulin Lispro in Children and Adolescents with Type 1 Diabetes Mellitus

ObjectiveTo provide a comprehensive review of insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in children and adolescents.MethodsWe performed PubMed literature searches to identify clinical studies of insulin lispro administered via CSII within pediatric and adolescent populations.ResultsTwenty-six studies involving 2521 pediatric patients with type 1 diabetes mellitus met inclusion criteria. Of these, 10 were randomized controlled trials (RCTs), 6 of which compared insulin lispro CSII with multiple daily injection (MDI) therapy. We identified 7 additional prospective, nonrandomized studies and 9 retrospective studies. Within the RCTs, endpoint hemoglobin A_1c levels ranged from 6.3% to 8.5% for insulin lispro CSII therapy and from 6.2% to 8.7% for those trials with MDI comparator arms. In those trials that compared insulin lispro CSII with MDI, the endpoint hemoglobin A_1c achieved with insulin lispro was similar or improved compared with observations in the MDI treatment arm. In the RCTs, severe hypoglycemia rates of 0.1 to 0.3 episodes/patient per year were reported for insulin lispro CSII therapy; those trials with MDI comparator arms reported relatively similar severe hypoglycemia rates (0.1 to 0.5 episodes/patient per year). Events of diabetic ketoacidosis (DKA) were rare. Where reported, insulin lispro CSII and MDI therapy demonstrated a similar occurrence of DKA and incidence of severe hypoglycemia. Prospective and retrospective studies demonstrated results similar to the RCT findings.ConclusionsIn 26 studies of more than 2500 pediatric and adolescent patients with type 1 diabetes, with more than 1000 patients specifically receiving insulin lispro CSII, insulin lispro CSII therapy consistently demonstrated similar or improved efficacy and safety vs studied comparators. (Endocr Pract. 2012;18:418-424)     

Assessment of Insulin Infusion Requirements in COVID-19-Infected Patients With Diabetic Ketoacidosis

Background/ObjectiveCoronavirus disease 2019 (COVID-19) is thought to contribute to diabetic ketoacidosis (DKA) and worse outcomes in patients with diabetes. This study compared the cumulative insulin dose required to achieve DKA resolution in the intensive care unit among patients with type 2 diabetes and COVID-19 infection versus without COVID-19 infection.MethodsThis retrospective cohort study evaluated 100 patients—50 patients with COVID-19 in cohort 1 and 50 patients without COVID-19 in cohort 2—treated with insulin infusions for DKA at a tertiary care teaching hospital. The primary outcome was to compare the cumulative insulin dose required to achieve DKA resolution in each cohort. The secondary outcomes included time to DKA resolution, mean insulin infusion rate, and mean weight-based cumulative insulin infusion dose required to achieve DKA resolution. All endpoints were adjusted for confounders.ResultsThe mean cumulative insulin dose was 190.3 units in cohort 1 versus 116.4 units in cohort 2 (P = .0038). Patients receiving steroids had a mean time to DKA resolution of 35.9 hours in cohort 1 versus 15.6 hours in cohort 2 (P = .0014). In cohort 1 versus cohort 2, the mean insulin infusion rate was 7.1 units/hour versus 5.3 units/hour (P = .0025), whereas the mean weight-based cumulative insulin infusion dose was 2.1 units/kg versus 1.5 units/kg (P = .0437), respectively.ConclusionCOVID-19-infected patients required a significantly larger cumulative insulin dose, longer time to DKA resolution, higher insulin infusion rate, and higher weight-based insulin infusion dose to achieve DKA resolution versus non–COVID-19-infected patients with type 2 diabetes.     

Clinical Experience with U500 Insulin: Risks and Benefits

ObjectiveTo describe our clinical experience with U500 insulin in insulin-resistant patients, including change in glucose control, body weight, insulin dose, and hypoglycemic episodes.MethodsIn September 2010, we undertook a retrospective chart review of patients who had U500 insulin in their medication list in the preceding 2 years who were treated in the endocrinology section at Dartmouth Hitchcock Medical Center. Glycosylated hemoglobin (A1C), body weight, and insulin dosage were documented before U500 insulin introduction, after 6 months of U500 insulin use, and at the last clinic visit when the patient was still taking U500 insulin. Hypoglycemic episodes and number of daily injections were recorded.ResultsRecords of 53 patients were analyzed, one of the largest reports of U500 insulin use published to date. The mean A1C level decreased from 10.1% before U500 insulin was initiated to 9.1% after 6 months of U500 use to 8.6% at the last follow-up visit (mean follow-up was 36.6 ± 24 months). At the last charted visit, body weight increased by a mean of 6.8 kg and insulin dosage increased by a mean of 0.44 units/kg. We observed a significant increase in the number of nonsevere hypoglycemic episodes and a decrease in the number of daily injections.ConclusionPatients with uncontrolled, severely insulin-resistant diabetes can be satisfactorily treated with U500 insulin with the potential to improve glycemic control. An increase in body weight, insulin dosage, and the number of nonsevere hypoglycemic episodes was observed. (Endocr Pract. 2012;18:56-61)     

Venous Serum Bicarbonate Concentration Predicts Arterial pH in Adults with Diabetic Ketoacidosis

ObjectiveThe initial assessment of metabolic acidosis in subjects with diabetic ketoacidosis (DKA) is arterial blood gas analysis. This process is expensive, painful, and technically difficult. Furthermore, blood gas analysis may not be available in some facilities, especially in developing countries where DKA-associated morbidity and mortality remain high. Therefore, we investigated the utility of venous bicarbonate concentration obtained from a basic metabolic panel in predicting arterial pH in adults with DKA.MethodsWe performed a retrospective analysis of clinical and biochemical data of 396 adults admitted to 2 community teaching hospitals with DKA. We determined the correlation between arterial pH and venous serum parameters. Using multiple logistic regression, we obtained a predictive formula for arterial pH from serum venous bicarbonate level.ResultsThe patient population was 59.0% male and had a mean age of 36.7 ± 13.3 years. We derived that arterial pH = 6.97 + (0.0163 × bicarbonate), and by applying this equation, we determined that serum venous bicarbonate concentration of ≤ 20.6 mEq/L predicted arterial pH ≤ 7.3 with over 95% sensitivity and 92% accuracy.ConclusionVenous serum bicarbonate obtained from the basic metabolic panel is an affordable and reliable way of estimating arterial pH in adults with DKA. Validation of this formula in a prospective study would offer a more accessible means of estimating metabolic acidosis in adults with DKA, especially in developing countries where DKA incidence and mortality remain high. (Endocr Pract. 2014;20:201-206)     

Causes and Predictors for 30-DAY Re-Admissions in Adult Patients with Diabetic Ketoacidosis in the United States: a Nationwide Analysis, 2010–2014

Objective: We aimed to determine the causes and predictors for 30-day re-admission following a hospitalization for diabetic ketoacidosis (DKA) in the United States.Methods: This retrospective cohort study analyzed data from the National Re-admission Database. We included adult patients with a primary discharge diagnosis of DKA, from 2010 to 2014. Our primary objective was to determine the frequency and causes for 30-day re-admission after an index hospitalization for DKA. We also performed multivariate regression analyses using covariates from the index admission to identify predictors for 30-day re-admissions.Results: Among 479,590 admissions for DKA, 58,961 (12.3%) were re-admitted within 30 days. Recurrent DKA represented 40.8% of all-cause re-admissions. In multivariate analysis, end-stage renal disease (odds ratio &lsqb;OR], 2.13; 95% confidence interval &lsqb;CI], 2.00 to 2.27; P<.001), Charlson Comorbidity Index ≥3 (OR, 2.49; 95% CI, 2.42 to 2.58; P<.001), discharge against medical advice (OR, 1.97; 95% CI, 1.86 to 2.09; P<.001), and drug use (OR, 1.78; 95% CI, 1.71 to 1.86; P<.001) were the most significant predictors for 30-day re-admission. About 50% of patients were re-admitted within 2 weeks after discharge.Conclusion: In the U.S., about one in every eight patients with DKA is re-admitted within 30 days, with 40.8% representing recurrent DKA episodes. Patients with end-stage renal disease, high comorbidity burden, drug use, and/or leaving against medical advice represented the highest risk group for re-admissions. Future studies with interventions focusing on high-risk population are critically needed.Abbreviations: AKI = acute kidney injury; BMI = body mass index; CCI = Charlson Comorbidity Index; CI = confidence interval; DKA = diabetic ketoacidosis; DM1 = type 1 diabetes mellitus; DM2 = type 2 diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Classification of Diseases, Ninth Edition, Clinical Modification; IQR = interquartile range; LOS = length of stay; NRD = National Re-admission Database; OR = odds ratio     

Safety and Efficacy of Glucostabilizer in the Management of Diabetic Ketoacidosis

Objective: To evaluate the safety and efficacy of GlucoStabilizer software intravenous insulin (IV) dosing in comparison to American Diabetes Association protocol-directed provider-guided insulin dose adjustment (PGIA).Methods: GlucoStabilizer calculates the dose of IV insulin required to reach a prescribed target glucose range. GlucoStabilizer has not been fully studied in DKA. This retrospective study compared outcomes in patients with DKA before and after the implementation of GlucoStabilizer. Insulin doses were administered based on GlucoStabilizer calculations or PGIA. The analysis evaluated before-after changes in the amount of insulin used, time to target, hypoglycemia or hypokalemia events, and the time to DKA resolution.Results: We studied 77 patients with insulin doses calculated by GlucoStabilizer and 69 patients with PGIA dosing. GlucoStabilizer was superior to PGIA. Patients treated with GlucoStabilizer-calculated doses did not experience hypoglycemia (N = 0 versus N = 10; P<.001). The 10 unique PGIA patients had a total of 18 episodes with 17 between 55 to 69 mg/dL; 1 <54 mg/dL, and no episodes <40 mg/dL. The GlucoStabilizer group required less insulin to reach DKA resolution (59.2 versus 101.2 units; P<.001). Time to glycemic target and DKA resolution were similar (6.7 versus 4.6 hours; P = .132) and (9.8 versus 9.9 hours; P = .803), respectively. No difference in the incidence of hypokalemia was seen (N = 9 versus N = 11; P = .48).Conclusion: This study demonstrates the Gluco Stabilizer settings that can be successfully used in the management of DKA with the avoidance of hypoglycemia. Patients treated with GlucoStabilizer-calculated doses experienced no hypoglycemia and required less insulin as compared to those managed with PGIA.Abbreviations: ADA = American Diabetes Association; DKA = diabetic ketoacidosis; ED = emergency department; eGMS = electronic glycemic management systems; ICU = intensive care unit; IV = intravenous; PGIA = protocol-directed provider-guided insulin dose adjustment     

Addressing Pitfalls in Management of Diabetic Ketoacidosis with a Standardized Protocol

Objective: To determine the efficacy and safety of a diabetic ketoacidosis (DKA)-Power Plan (PP) for guiding intravenous (IV) insulin infusions prior to anion gap (AG) closure and administering subcutaneous (SC) insulin ≥1 hour before discontinuing IV insulin.Methods: Retrospective chart review of patients with DKA before (pre-PP) (n = 60) and following (post-PP) (n = 60) implementation of a DKA-PP. Groups were compared for percentage of patients for whom IV insulin therapy was continued until AG closure, the percentage of patients receiving SC insulin ≥1 hour before discontinuation of IV insulin, and percentage of patients with rebound DKA during the index hospitalization.Results: Admission plasma glucose (514 mg/dL vs. 500 mg/dL; P = .36) and venous pH (7.2 vs. 7.2; P = .57) were similar in pre- and post-PP groups. Inappropriate discontinuation of IV insulin occurred less frequently in post-PP patients (28% vs. 7%; P = .007), with a lower frequency of rebound DKA (40% vs. 8%; P = .001) following acute management. More post-PP patients received SC insulin ≥1 hour before discontinuation of IV insulin (65% vs. 78%; P = .05).Conclusion: Implementation of a DKA-PP was associated with appropriate discontinuation of IV insulin in more patients, more frequent administration of SC insulin ≥1 hour prior to discontinuation of IV insulin, and fewer episodes of rebound DKA.Abbreviations: ADA = American Diabetes Association; AG = anion gap; BG = blood glucose; DKA = diabetic ketoacidosis; DKA-PP = DKA-Power Plan; ICU = intensive care unit; IQR = interquartile range; IV = intravenous; IVF = IV fluid; LOS = length of stay; SC = subcutaneous     

C-Peptide and Beta-Cell Autoantibody Testing Prior to Initiating Continuous Subcutaneous Insulin Infusion Pump Therapy Did Not Improve Utilization Or Medical Costs Among Older Adults With Diabetes Mellitus

Objective: To study the impact of the C-peptide and beta-cell autoantibody testing required by the Center for Medicare and Medicaid Services (CMS) on costs/utilization for patients with diabetes mellitus initiating continuous subcutaneous insulin infusion (CSII) therapy.Methods: This retrospective study used propensity score–matched patients. Analysis 1 compared patients 1-year pre- and 2-years post-CSII adoption who met or did not meet CMS criteria. Analysis 2 compared Medicare Advantage patients using CSII or multiple daily injections (MDI) who did not meet CMS criteria for 1-year pre- and 1-year post-CSII adoption. Analysis 3 extended analysis 2 to 2 years postindex and also included a subset of patients ≥55 years old but not yet in Medicare Advantage.Results: Analysis 1 resulted in significantly slower growth in hospital admissions (P =.0453) in CSII-treated patients who did not meet the criteria. Analyses 2 and 3 showed numerically slower growth in inpatient, outpatient, and emergency department (ED) costs for CSII versus MDI patients (both not meeting criteria). Analysis 3 showed significantly slower growth in ED costs and hospital admissions for CSII versus MDI Medicare Advantage patients before propensity matching (both P<.05). In patients ≥55 years old, ED costs grew more slowly for CSII than MDI therapy (P =.0678).Conclusion: Numerically slower growth in hospital admissions was seen for pump adopters who did not meet CMS C-peptide criteria, while medical costs growth was similar. For CSII users who did not meet the CMS criteria, numerically slower growth in inpatient, outpatient, ED costs, and hospital admissions occurred versus MDI.Abbreviations: CMS = Center for Medicare and Medicaid Services; CSII = continuous subcutaneous insulin infusion; DM = diabetes mellitus; DME = durable medical equipment; ED = emergency department; MDI = multiple daily injections (of insulin)     

Postmortem Diagnosis of Diabetic Ketoacidosis Presenting as the "Dead-in-Bed Syndrome"

Objective:To report a case of a young male with type 1 diabetes mellitus found dead in his bed, initially assumed to have died from hypoglycemia (i.e., the “dead in bed” syndrome). However, his autopsy findings revealed that diabetic ketoacidosis (DKA) was the cause of death.MethodsWe present the laboratory and autopsy findings of the patient, highlighting the importance of laboratory analyses of the vitreous humor and microscopy of kidney tissue when investigating the cause of sudden death in patients with type 1 diabetes.ResultsA 25-year-old healthy male with type 1 diabetes on continuous subcutaneous insulin infusion therapy was found dead in his undisturbed bed. An autopsy included vitreous humor analyses. His results were as follows: glucose of 755 mg/dL (reference range 70-105 mg/dL), anion gap > 36 mEq (reference range 4-12 mEq/L), elevated acetone at 66 mg/dL (reference range negative), which were consistent with DKA. Renal microscopy demonstrated subnuclear vacuoles in the proximal tubules, 1 of 2 lesions were described as an Armanni-Ebstein lesion, which is a postmortem finding in patients who die from diabetic coma.ConclusionThe most likely cause of death at home in young patients with type 1 diabetes is severe hypoglycemia. However, an autopsy of the present case confirmed DKA based on vitreous humor biochemistry and microscopic examination of the kidneys, which demonstrated the Armanni-Ebstein phenomenon. Analysis of the vitreous fluid and microscopic examination of the kidneys for the presence of Armanni-Ebstein lesion can be used to help determine the cause of death in patients with type 1 diabetes mellitus. (Endocr Pract. 2014;20:e123-e125)     

Preserved Proinsulin Production in Homozygous Protein Tyrosine Phosphatase Nonreceptor Type 22 C1858T Variant Type 1 Diabetes: A Possible Explanation for Absence of Overt Ketoacidosis Despite Omission of Exogenous Insulin

ObjectiveTo report a postulated mechanism for resistance to overt ketoacidosis due to prolonged insulin omission in a severely hyperglycemic woman with a 14-year history of autoimmune type 1 diabetes (T1D).MethodsHistory, physical examination, laboratory testing, and genotyping were performed. We also review the medical literature pertinent to this patient’s phenotype and genotype.ResultsProinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia. We confirmed a homozygous (TT) variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22) 1858T, a T1D susceptibility gene associated with higher proinsulin levels.ConclusionThe extraordinarily preserved proinsulin biological activity may explain the unusual resistance to overt ketoacidosis despite omission of exogenous insulin administration for extended periods of time. The role of the associated PTPN22 1858TT variant remains speculative. (Endocr Pract. 2013;19:426-430)     

Impact of Multidisciplinary Process Improvement Interventions on Glucometrics in a Noncritically Ill Setting

Objective: This study aimed to assess the impact of multidisciplinary process improvement interventions on glycemic control in the inpatient setting of an urban community hospital, utilizing the daily simple average as the primary glucometric measure.Methods: From 2010–2014, five process of care interventions were implemented in the noncritical care inpatient units of the study hospital. Interventions included education of medical staff, implementation of hyperglycemia and hypoglycemia protocols, computerized insulin order entry, and coordination of meal tray delivery with finger stick and insulin administration. Unpaired t tests compared pre- and postintervention process measures. Simple average daily glucose measure was the primary glucometric outcome. Secondary outcome measures included frequency of hyperglycemia and hypoglycemia. Glucose outcomes were compared with an in-network hospital that did not implement the respective interventions.Results: A total of 180,431 glucose measurements were reported from 4,705 and 4,238 patients from the intervention and comparison hospitals, respectively. The time between bolus-insulin administration and breakfast tray delivery was significantly reduced by 81.7 minutes (P<.00005). The use of sliding scale insulin was sustainably reduced. Average daily glucose was reduced at both hospitals, and overall rates of hypoglycemia were low.Conclusion: A multidisciplinary approach at an urban community hospital with limited resources was effective in improving and sustaining processes of care for improved glycemic control in the noncritical care, inpatient setting.Abbreviations: IQR = interquartile range; JMC = Jacobi Medical Center; NCBH = North Central Bronx Hospital     

Disparities in Utilization and Outcomes With Continuous Subcutaneous Insulin Infusion in Young Adults With Type 1 Diabetes

ObjectiveTo evaluate which factors determine utilization patterns and outcomes of continuous subcutaneous insulin infusion (CSII) in young adults with type 1 diabetes.MethodsUtilizing the Optum deidentified electronic health record data set between 2008 to 2018 to perform a retrospective cohort study, we identified 2104 subjects with type 1 diabetes aged 18 to 30 years. We evaluated the effect of race on determining CSII utilization, HbA1c (%), and hospital admission for diabetic ketoacidosis (DKA). Crude and adjusted estimates were computed using logistic regression and linear mixed models.ResultsThere was low CSII utilization among individuals who were Black, Hispanic, male, and those with governmental insurance. These groups also demonstrated higher HbA1c levels. Subjects who were Black, Hispanic, and those with governmental insurance had higher odds of DKA. Even when commercially insured, Black and Hispanic subjects demonstrated higher HbA1c levels, and Black individuals had higher odds of DKA.ConclusionIn a large electronic health record database in the U.S., there was low CSII utilization overall, particularly in Black and Hispanic minorities, despite CSII showing superior HbA1c control without an increase in DKA events.     

Flash Glucose Monitoring Compared to Capillary Glucose Levels in Patients With Diabetic Ketoacidosis: Potential Clinical Applications

ObjectiveFrequent, finger-prick capillary blood glucose measurement is standard care, used to drive insulin infusion rates for inpatients being resuscitated from diabetic ketoacidosis (DKA). Over recent years there has been a shift toward continuous interstitial glucose monitoring, allowing monitoring of glucose without repeated invasive testing. While continuous interstitial glucose monitoring has been safely and reliably utilized in the outpatient setting, it has yet to be studied in acutely unwell patients with DKA. The aim of this study, allowing for physiologically lower interstitial compared to capillary glucose, was to determine if interstitial flash glucose monitoring (FGM) would lead to insulin infusion rates that were similar to capillary blood glucose (CapBG) in DKA.MethodsIn this study, 10 patients with diabetes mellitus, assessed to be in DKA, were enrolled. At the same time as standard DKA management commencement, simultaneous FGM measurements were obtained. Duplicate paired glucose readings were then analyzed for agreement.ResultsActual (CapBG-driven) and predicted (FGM determined) insulin infusion rates were similar. Minor differences in predicted insulin infusion rates were noted in 2/10 patients at higher glucose concentrations, which may relate to the lag in change in glucose in the interstitial space.ConclusionBased on our results, a trial of clinical outcomes in patients with DKA treated with insulin infusion rates driven by CapBG versus subcutaneous FGM appears justified. The FGM method of testing may improve patient comfort, obviate fatigue, improve staff time and direct patient contact, and potentially facilitate rapid discharge.     

Hypoglycemia: Still The Limiting Factor in the Glycemic Management of Diabetes

ObjectiveTo review the prevalence of, risk factors for, and prevention of hypoglycemia from the perspective of the pathophysiologic aspects of glucose counterregulation in diabetes.MethodsThis review is based on personal experience and research and the relevant literature.ResultsAlthough it can result from insulin excess alone, iatrogenic hypoglycemia is generally the result of the interplay of therapeutic insulin excess and compromised defenses against declining plasma glucose concentrations. Failure of β-cells of the pancreas—early in patients with type 1 diabetes mellitus but later in those with type 2 diabetes mellitus (T2DM)—causes loss of the first 2 physiologic defenses: a decrease in insulin and an increase in glucagon. Such patients are critically dependent on epinephrine, the third physiologic defense, and neurogenic symptoms that prompt the behavioral defense (carbohydrate ingestion). An attenuated sympathoadrenal response to declining glucose levels—caused by recent antecedent hypoglycemia, prior exercise, or sleep—causes hypoglycemia-associated autonomic failure (HAAF) and thus a vicious cycle of recurrent hypoglycemia. Accordingly, hypoglycemia is infrequent early in T2DM but becomes increasingly more frequent in advanced (absolutely endogenous insulin-deficient) T2DM, and risk factors for HAAF include absolute endogenous insulin deficiency; a history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se.ConclusionBy practicing hypoglycemia risk reduction— addressing the issue, applying the principles of aggressive glycemic therapy, and considering both the conventional risk factors and those indicative of HAAF— it is possible both to improve glycemic control and to minimize the risk of hypoglycemia in many patients. (Endocr Pract. 2008;14:750-756)     

Factors Associated With Insulin Pump Discontinuation in Adults With Diabetes: A Time-to-Invent Analysis and Prediction Model

ObjectiveInsulin pump discontinuation has mostly been studied in children and adolescents living with diabetes. We aimed to assess the rate of insulin pump continuation in a population of adult patients with diabetes, at 18 months after initiation; determine the factors associated with pump discontinuation; and develop a simple prediction model.MethodsThis single-center, retrospective study included all adult patients with type 1 diabetes or type 2 diabetes who started insulin pump treatment between January 2015 and June 2018. The exclusion criteria were pregnancy, short-term pregnancy plans, and insulin pump discontinuation within the previous 6 months. The probability of insulin pump continuation after 18 months was estimated using the Kaplan-Meier method. Factors associated with insulin pump discontinuation were studied using a Cox regression model, and an exponential model was built for prediction purposes.ResultsThe study included 315 patients. The mean age was 41 years, the mean duration of diabetes was 16 years, 50% were men, 74% had type 1 diabetes, and the mean hemoglobin A1c level was 9.1% (76 mmol/mol). After 18 months, the rate of insulin pump continuation was 0.80 (95% Confidence Interval (CI), 0.76-0.85). By multivariate analysis, the occurrence of severe hypoglycemia in the previous year was associated with insulin pump discontinuation (hazard ratio, 2.42; 95% CI, 1.30-4.51), while other factors did not reach statistical significance.ConclusionInsulin pump discontinuation occurred in 20% of patients at 18 months after initiation and was mainly associated with a recent history of severe hypoglycemia. The type of diabetes and glycemic control at baseline were not associated with treatment discontinuation.     

Confirmation of Hypoglycemia in the “Dead-In-Bed” Syndrome,as Captured by a Retrospective Continuous Glucose Monitoring System

ObjectiveTo report a case that substantiates the presence of hypoglycemia at the time of death of a young man with type 1 diabetes, who was found unresponsive in his undisturbed bed in the morning.MethodsWe describe a 23-year-old man with a history of type 1 diabetes treated with an insulin pump, who had recurrent severe hypoglycemia. In an effort to understand these episodes better and attempt to eliminate them, a retrospective (non-real-time) continuous subcutaneous glucose monitoring system (CGMS) was attached to the patient. He was found dead in his undisturbed bed 20 hours later. The insulin pump and CGMS were both downloaded for postmortem study.ResultsPostmortem download of the data in the CGMS demonstrated glucose levels below 30 mg/dL around the time of his death, with only a minimal counterregulatory response. This finding corresponded to a postmortem vitreous humor glucose of 25 mg/dL. An autopsy showed no major anatomic abnormalities that could have contributed to his death.ConclusionTo our knowledge, this is the first documentation of hypoglycemia at the time of death in a patient with the “dead-in-bed” syndrome. This report should raise the awareness of physicians to the potentially lethal effectsof hypoglycemia and provide justification for efforts directed at avoiding nocturnal hypoglycemia. (Endocr Pract. 2010;16:244-248)