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Aim: The transition to the ICD-10-CM coding system has reduced the utility of hypoglycaemia algorithms based on ICD-9-CM diagnosis codes in real-world studies of antidiabetic drugs. We mapped a validated ICD-9-CM hypoglycaemia algorithm to ICD-10-CM codes to create an ICD-10-CM hypoglycaemia algorithm and assessed its performance in identifying severe hypoglycaemia., Materials and Methods: We assembled a cohort of Medicare patients with DM and linked electronic health record (EHR) data to the University of North Carolina Health System and identified candidate severe hypoglycaemia events from their Medicare claims using the ICD-10-CM hypoglycaemia algorithm. We confirmed severe hypoglycaemia by EHR review and computed a positive predictive value (PPV) of the algorithm to assess its performance. We refined the algorithm by removing poor performing codes (PPV ≤0.5) and computed a Cohen's κ statistic to evaluate the agreement of the EHR reviews., Results: The algorithm identified 642 candidate severe hypoglycaemia events, and we confirmed 455 as true severe hypoglycaemia events, PPV of 0.709 (95% confidence interval: 0.672, 0.744). When we refined the algorithm, the PPV increased to 0.893 (0.862, 0.918) and missed <2.42% (<11) true severe hypoglycaemia events. Agreement between reviewers was high, κ  = 0.93 (0.89, 0.97)., Conclusions: We translated an ICD-9-CM hypoglycaemia algorithm to an ICD-10-CM version and found its performance was modest. The performance of the algorithm improved by removing poor performing codes at the trade-off of missing very few severe hypoglycaemia events. The algorithm has the potential to be used to identify severe hypoglycaemia in real-world studies of antidiabetic drugs., (© 2024 John Wiley & Sons Ltd.)

Background: There is a lack of consensus regarding the definition and treatment threshold for neonatal hypoglycaemia. The American Academy of Pediatrics (AAP) has a published clinical report making recommendations on practice guidelines. There is limited literature discussing the impact of these guidelines. In this study, we evaluated the screening and diagnosis of neonatal hypoglycaemia following the AAP guidelines., Methods: Infants born ≥35 weeks gestational age and admitted to the well-baby nursery between January and December 2017 were included in this study. Our hypoglycaemia policy was based on the AAP clinical report for hypoglycaemia management in newborns. Chart review was done to obtain infant hypoglycaemia risk factors and blood glucose values in the first 24 hours. Data analysis was conducted using Stata V.14.2 (StataCorp)., Results: Of 2873 infants born and admitted to the well-baby nursery, 32% had at least one hypoglycaemia risk factor and 96% of them were screened for hypoglycaemia. Screened infants were more likely to be born at a lower gestational age, via C-section, and to a multiparous older mother. Screened infants and hypoglycaemic infants had lower exclusive breastfeeding rates compared with those who were not screened or not hypoglycaemic, respectively. Sixteen per cent of screened infants were diagnosed with hypoglycaemia; 0.8% of at-risk screened infants and 5% of hypoglycaemic infants were admitted to the NICU for treatment of hypoglycaemia. Thirty-one per cent of preterm infants, 15% of large for gestational age infants, 13% of small for gestational age infants and 15% of infants of diabetic mothers were hypoglycaemic. Hypoglycaemic infants were more likely to be born preterm and via C-section., Conclusion: Using the AAP time-based definitional blood glucose cut-off values, our incidence of hypoglycaemia found in those who were screened for risk factors was lower compared with other studies. Future long-term follow-up studies will be important., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Administrative claims are commonly relied upon to identify hypoglycemia. We assessed validity of 14 International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code assignments to identify medication-related hypoglycemia leading to acute care encounters., Research Design and Methods: A multisite, retrospective medical record review study was conducted in a sample of Medicare beneficiaries prescribed outpatient diabetes medications and who received hospital care between January 1, 2016 and September 30, 2017. Diagnosis codes were validated with structured medical record review using prespecified criteria (clinical presentation, blood glucose values, and treatments for hypoglycemia). Sensitivity, specificity, and positive and negative predictive value (PPV, NPV) were calculated and adjusted using sampling weights to correct for partial verification bias., Results: Among 990 encounters (496 cases, 494 controls), hypoglycemia codes demonstrated moderate PPV (69.2%; 95% confidence interval: 65.0-73.0) and moderate sensitivity (83.9%; 95% confidence interval: 70.0-95.5). Codes performed better at identifying hypoglycemic events among emergency department/observation encounters compared with hospitalizations (PPV 92.9%, sensitivity 100.0% vs. PPV 53.7%, sensitivity 71.0%). Accuracy varied by diagnosis position, especially for hospitalizations, with PPV of 95.6% versus 46.5% with hypoglycemia in primary versus secondary positions. Use of adverse event/poisoning codes did not improve accuracy; reliance on these codes alone would have missed 97% of true hypoglycemic events., Conclusions: Accuracy of International Classification of Diseases, Tenth Revision codes in administrative claims to identify medication-related hypoglycemia varied substantially by encounter type and diagnosis position. Consideration should be given to the trade-off between PPV and sensitivity when selecting codes, encounter types, and diagnosis positions to identify hypoglycemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia., Materials and Methods: Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants., Results: There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05-1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00-1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60-0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate - 0.12 [SE 0.01]; ARV, - 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17-1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV., Conclusions: Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes., (© 2021. The Author(s).)

Background: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect., Methods: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population., Results: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe., Conclusion: The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objectives: To describe variations in the practice of hypoglycemia screening and treatment in asymptomatic infants in the United States., Methods: During the time period from February 2018 to June 2018, we surveyed representatives of hospitals participating in the Better Outcomes through Research for Newborns Network, a national research network of clinicians providing hospital care to term and late-preterm newborns. The survey included 22 questions evaluating practices related to hypoglycemia screening and management of asymptomatic infants., Results: Of 108 network sites, 84 (78%) responded to the survey; 100% had a hypoglycemia protocol for screening at-risk infants in the well-baby nursery. There were wide variations between sites regarding the definition of hypoglycemia (mg/dL) (<45 [24%]; <40 [23%]; <40 [0-4 hours] and <45 [4-24 hours] [27%]; <25 [0-4 hours] and <35 [4-24 hours] [8%]), timing of first glucose check (<1 hour [18%], 1-2 hours [30%], 30 minutes post feed [48%]), and threshold glucose level for treatment (<45 [19%]; <40 [18%]; <40 [0-4 hours] and <45 [4-24 hours] [20%]; <25 [0-4 hours] and <35 [4-24 hours] [15%]). All respondents used breast milk as a component of initial therapy. Criteria for admission to the NICU for hypoglycemia included the need for dextrose containing intravenous fluids (52%), persistent hypoglycemia despite treatment (49%), and hypoglycemia below a certain value (37%)., Conclusions: There is a significant practice variation in hypoglycemia screening and management across the United States., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with β-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known., Materials and Methods: We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication., Results: Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age: 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases., Conclusion: Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.

Background: Intraoperative hypoglycemia can result in devastating neurologic injury if not promptly diagnosed and treated. Few studies have defined risk factors for intraoperative hypoglycemia. The authors sought to characterize children with intraoperative hypoglycemia and determine independent risk factors in a multicenter cohort., Methods: This retrospective multicenter study included all patients <18 years undergoing an anesthetic from January 1, 2012, to December 31, 2016, at 12 institutions participating in the Multicenter Perioperative Outcomes Group (MPOG). The primary outcome was blood glucose <60 mg/dL (3.3 mmol/L). Data collected included patient characteristics, comorbidities, and intraoperative factors. A multivariable logistic regression model was used to identify independent predictors of intraoperative hypoglycemia., Results: Blood glucose was measured in 26,142 of 394,231 (6.6%) cases. Of these, 1017 (3.9%) had a glucose <60 mg/dL (3.3 mmol/L). Independent predictors for intraoperative hypoglycemia identified were age <30 days (estimated adjusted odds ratio [AOR] vs ≥5 years 4.2; 95% confidence interval [CI], 3.4-5.3), age 30 days to <5 years (estimated AOR vs ≥5 years 2.7; 95% CI, 2.3-3.2), weight for age <5th percentile (estimated AOR, 1.6; 95% CI, 1.4-1.9), American Society of Anesthesiologists (ASA) status ≥III (estimated AOR, 1.3; 95% CI, 1.1-1.6), presence of a gastric or jejunal tube (estimated AOR, 1.3; 95% CI, 1.1-1.6), poor feeding (estimated AOR, 1.5; 95% CI, 1.2-1.7), and abdominal surgery (estimated AOR, 1.4; 95% CI, 1.1-1.7). Eighty percent of hypoglycemia occurred in children <5 years of age and in children <20 kg., Conclusions: Young age, weight for age <5th percentile, ASA status ≥III, having a gastric or jejunal tube, poor feeding, and abdominal surgery were risk factors for intraoperative hypoglycemia in children. Monitoring of blood glucose is recommended in these subsets of children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

The incidence of hypoglycemia in the immediate postnatal period is rising because of the increasing rate of preterm births, maternal diabetes, and maternal obesity. Severe hypoglycemia has been considered a risk factor for neuronal cell death and adverse neurodevelopmental outcomes. The American Academy of Pediatrics (AAP) suggests a goal of ≥45 mg/dL (≥2.5 mmol/L) for infants who are asymptomatic within the first 48 hours. The Pediatric Endocrine Society (PES) suggests that infants who are unable to maintain their blood glucose >50 mg/dL (>2.77 mmol/L) within the first 48 hours or >60 mg/dL (>3.33 mmol/L) after the first 48 hours are at risk for persistent hypoglycemia. While there is disagreement for target glucose levels within the first 48 hours, both the AAP and the PES suggest further investigation for persistent hypoglycemia beyond 48-72 hours, which is beyond the scope of this article. However, in the immediate postnatal period, much can be gained with familiarization of the two guidelines, as well as current management techniques. This article presents current definitions and treatment modalities for management of hypoglycemia in infants considered at high risk in the immediate postnatal period., (© Copyright 2020 Springer Publishing Company, LLC.)

Objective: To determine if natural language processing (NLP) improves detection of nonsevere hypoglycemia (NSH) in patients with type 2 diabetes and no NSH documentation by diagnosis codes and to measure if NLP detection improves the prediction of future severe hypoglycemia (SH)., Research Design and Methods: From 2005 to 2017, we identified NSH events by diagnosis codes and NLP. We then built an SH prediction model., Results: There were 204,517 patients with type 2 diabetes and no diagnosis codes for NSH. Evidence of NSH was found in 7,035 (3.4%) of patients using NLP. We reviewed 1,200 of the NLP-detected NSH notes and confirmed 93% to have NSH. The SH prediction model (C-statistic 0.806) showed increased risk with NSH (hazard ratio 4.44; P < 0.001). However, the model with NLP did not improve SH prediction compared with diagnosis code-only NSH., Conclusions: Detection of NSH improved with NLP in patients with type 2 diabetes without improving SH prediction., (© 2020 by the American Diabetes Association.)

Objective: Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system., Research Design and Methods: After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14-72 years; mean HbA 1c , 7.1% [54 mmol/mol]) were randomly assigned to CLC ( N = 54, Control-IQ) or PLGS ( N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70-180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study., Results: All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P < 0.001). Time >180 mg/dL was lower in the CLC group than PLGS group (difference = -6.0%; 95% CI -8.4%, -3.7%; P < 0.001) while time <54 mg/dL was similar (0.04%; 95% CI -0.05%, 0.13%; P = 0.41). HbA 1c after 13 weeks was lower on CLC than PLGS (7.2% [55 mmol/mol] vs. 7.5% [56 mmol/mol], difference -0.34% [-3.7 mmol/mol]; 95% CI -0.57% [-6.2 mmol/mol], -0.11% [1.2 mmol/mol]; P = 0.0035)., Conclusions: Following 6 months of CLC, switching to PLGS reduced TIR and increased HbA 1c toward their pre-CLC values, while hypoglycemia remained similarly reduced with both CLC and PLGS., (© 2020 by the American Diabetes Association.)

Background: While the association between hypoglycaemia and poor outcomes in diabetes is well established, it is unclear whether such an association is generalizable to those without diabetes., Methods: A total of 8497 participants free of cardiovascular disease and diabetes from the Third National Health and Nutrition Examination Survey were included. We examined the relationship between baseline low (<80 mg/dL) and high (⩾126 mg/dL) fasting plasma glucose compared to normal levels (80-99 mg/dL)., Results: Over a median follow-up of 14 years, 2101 deaths occurred, of which 570 were due to cardiovascular disease. In a model adjusted for sociodemographic and cardiovascular disease risk factors, individuals with low fasting plasma glucose were at increased risk of cardiovascular disease and all-cause mortality [hazard ratio = 1.79 (95% confidence interval = 1.04-3.08) and hazard ratio = 1.35 (95% confidence interval = 1.02-1.78), respectively], compared to those with normal fasting plasma glucose. These associations were stronger among men than women for both cardiovascular disease mortality and all-cause mortality., Conclusion: Low fasting plasma glucose in individuals without diabetes is a risk factor for cardiovascular disease and all-cause mortality, especially in men.

Background: Continuous glucose monitoring (CGM) offers multiple data features that can be leveraged to assess glucose management. However, how diabetes healthcare professionals (HCPs) actually assess CGM data and the extent to which they agree in assessing glycemic management are not well understood., Methods: We asked HCPs to assess ten de-identified CGM datasets (each spanning seven days) and rank order each day by relative glycemic management (from "best" to "worst"). We also asked HCPs to endorse features of CGM data that were important in making such assessments., Results: In the study, 57 HCPs (29 endocrinologists; 28 diabetes educators) participated. Hypoglycemia and glycemic variance were endorsed by nearly all HCPs to be important (91% and 88%, respectively). Time in range and daily lows and highs were endorsed more frequently by educators (all P s < .05). On average, HCPs endorsed 3.7 of eight data features. Overall, HCPs demonstrated agreement in ranking days by relative glycemic control (Kendall's W = .52, P < .001). Rankings were similar between endocrinologists and educators ( R 2 = .90, Cohen's kappa = .95, mean absolute error = .4 [all P s < .05]; Mann-Whitney U = 41, P = .53)., Conclusions: Consensus in the endorsement of certain data features and agreement in assessing glycemic management were observed. While some practice-specific differences in feature endorsement were found, no differences between educators and endocrinologists were observed in assessing glycemic management. Overall, HCPs tended to consider CGM data holistically, in alignment with published recommendations, and made converging assessments regardless of practice.

Objective: To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials., Research Design and Methods: A post hoc analysis was performed of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and DEVOTE ( n = 7,637, type 2 diabetes) trials utilizing the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1 ) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2 ) IHSG level 2 (PG confirmed <3.0 mmol/L, independent of symptoms)., Results: In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. Similar results were observed for the SWITCH 1 trial. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition., Conclusions: The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials., (© 2019 by the American Diabetes Association.)

Background/aim: Episodes of non-severe hypoglycemia can be captured through diagnoses documented in the electronic medical record. We aimed to create a clinically useful prediction model for a severe hypoglycemia event, requiring an emergency department visit or hospitalization, in patients with Type 2 diabetes with a history of non-severe hypoglycemia., Methods: Using electronic medical record data from 50,439 patients with Type 2 diabetes in one health system, number of severe hypoglycemia events and associated patient characteristics from 2006 to 2015 were previously defined. Using the landmarking method, a dynamic prediction model was built using the subset of 1876 patients who had a documented non-severe hypoglycemia diagnosis code, using logistic regression to obtain landmark-specific odds of severe hypoglycemia in this group. For model performance, the bootstrap procedure was employed for internal validation and area under the curve (AUC) and index of prediction accuracy (IPA) were calculated., Results: Glycosylated hemoglobin (HbA1c) less than 7% (53 mmol/mol) was associated with increased odds ratio (OR) of severe hypoglycemia at 3 months (OR 1.92 95% Confidence Interval (CI) 1.19-3.10 at HbA1c 5% (31 mmol/mol) and OR 1.21, CI 1.03-1.41 at HbA1c 6%(42 mmol/mol).) History of non-severe hypoglycemia within the past 3 months increased odds for severe hypoglycemia (OR 2.58 95% CI 1.80-3.70) as did Black race, insulin use with the past 3 months, and comorbidities. Metformin and sulfonlylurea use in the past 3 months, increasing age and body mass index had lower odds of a future severe hypoglycemia event. For the prediction model for 3 month risk of severe hypoglycemia, the AUC was 0.890 (CI 0.843-0.907) and the IPA was 10.8% (CI 4.4% - 12.4%)., Conclusion: In patients with a documented diagnosis of non-severe hypoglycemia, a dynamic prediction model identifies patients with Type 2 diabetes with 3-month increased risk of severe hypoglycemia, allowing for preventive efforts, such as medication changes, at the point of care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prior research suggests that warfarin, when given concomitantly with some sulfonylureas, may increase the risk of serious hypoglycemia. However, the clinical significance remains unclear. We examined rate ratios (RRs) for the association between serious hypoglycemia and concomitant use of warfarin with either sulfonylureas or metformin using a self-controlled case series design and US Medicaid claims (supplemented with Medicare claims) from 1999 to 2011. Across all risk windows combined, warfarin was associated with an elevated rate of serious hypoglycemia when given concomitantly with glimepiride (RR, 1.47; 95% confidence interval (CI), 1.07-2.02) and metformin (RR, 1.73; 95% CI, 1.38-2.16). Particularly in the late risk window (>120 days since beginning concomitancy), most of the RRs for warfarin were elevated: glipizide (RR, 1.72; 95% CI, 1.29-2.29), glyburide (RR, 1.57; 95% CI, 1.15-2.15), metformin (RR, 2.26; 95% CI, 1.67-3.05), and glimepiride (RR, 1.56; 95% CI, 0.97-2.50). These results are consistent with a previously hypothesized hypoglycemic effect of warfarin in patients with type 2 diabetes through inhibition of the carboxylation of osteocalcin., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Background: Practice guidelines recommend against intensive insulin therapy in patients who are critically ill based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized IV insulin protocol that allows choice of blood glucose (BG) targets (80-110 vs 90-140 mg/dL) and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac ICUs that have very low rates of severe hypoglycemia., Methods: Critically ill patients receiving IV insulin were treated with either of two BG targets (80-110 vs 90-140 mg/dL). We created a propensity score for BG target using factors thought to have influenced clinicians' choice, and then we performed a propensity score-adjusted regression analysis for 30-day mortality., Results: There were 1,809 patients who met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110 mg/dL group (104 vs 122 mg/dL, P < .001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs 0.35%, P = .051). Unadjusted 30-day mortality was lower in the 80-110 mg/dL group (4.3% vs 9.2%, P < .001). This remained after propensity score-adjusted regression (OR, 0.65; 95% CI, 0.43-0.98; P = .04)., Conclusions: Tight glucose control can be achieved with low rates of severe hypoglycemia and is associated with decreased 30-day mortality in a cohort of largely patients in cardiac ICUs. Although such findings should not be used to guide clinical practice at present, the use of tight glucose control should be reexamined using a protocol that has low rates of severe hypoglycemia., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the proportion of older adults with diabetes mellitus treated with tight glucose control and the factors associated with this practice., Design: Cross-sectional analysis., Setting: Outpatient sites in the Diabetes Collaborative Registry (N=151)., Participants: Adults aged 75 and older with type 2 diabetes mellitus (N=42,669)., Measurements: Participants were categorized based on glycosylated hemoglobin (HbA1c) and glucose-lowering medications: poor control (HbA1c >9%), moderate control (HbA1c 8-9%), conservative control (HbA1c 7-8%), tight control (HbA1c <7%) with low-risk agents (low risk for hypoglycemia), tight control with high-risk agents, and diet control (HbA1c <7% taking no glucose-lowering medications). We used hierarchical logistic regression to examine participant and site factors associated with tight control and high-risk agents versus conservative or tight control and low-risk agents., Results: Of 30,696 participants without diet-controlled diabetes, 5,596 (18%) had moderate or poor control, 9,227 (30%) had conservative control, 7,893 (26%) had tight control taking low-risk agents, and 7,980 (26%) had tight control taking high-risk agents. Older age, male sex, heart failure, chronic kidney disease, and coronary artery disease were each independently associated with greater odds of tight control with high-risk agents. There were no differences according to practice specialty (endocrinology, primary care, cardiology) in how aggressively participants were managed., Conclusion: One-quarter of U.S. older adults with type 2 diabetes mellitus are tightly controlled with glucose-lowering medications that have a high risk of hypoglycemia. These results suggest potential overtreatment of a substantial proportion of people and should encourage further efforts to translate guidelines to daily practice., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Objective: To describe patient and provider characteristics for patients with type 2 diabetes (T2DM) initiating basal insulin and describe basal insulin's impact on sulfonylurea (SU) discontinuation., Methods: A retrospective cohort study was conducted using the HealthCore Integrated Research Database. Patients had ≥12 months of continuous coverage prior to initiating insulin, and were utilizing at least one anti-hyperglycemic drug at the time of insulin initiation. Predictors for SU discontinuation were evaluated utilizing Cox proportional hazards models., Results: Among the 74,334 individuals aged ≥18 years with T2DM who initiated basal insulin from 2006-2015, 30% were taking metformin (MET) and SU when initiating insulin. Among the 22,418 MET/SU patients, 31% discontinued SU within 3 months of insulin initiation and, by 12 months, 55% had discontinued SU. Sulfonylurea discontinuation was similar among many patient and provider characteristics, while being modestly positively associated (p < .05; HRs <1.5) with female gender, more co-morbidities, cardiac revascularization, chronic liver disease, hospitalizations with a T2DM diagnosis, and hypoglycemia prior to insulin initiation. SU discontinuation was modestly inversely associated with receiving an insulin prescription from an endocrinologist (HR = 0.90, 95% CI = 0.85-0.95)., Conclusions: Roughly half of commercially-insured T2DM patients discontinued SU within 1 year after insulin initiation, and SU discontinuation was not strongly associated with a range of patient and provider characteristics.

Purpose: To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy-treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione., Methods: We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania. We did not include users of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, or sodium-glucose co-transporter 2 inhibitors. We identified serious hypoglycemia outcomes within 180 days following new use using a validated, diagnosis-based algorithm. We calculated age- and sex-standardized outcome occurrence rates for each drug and generated propensity score-adjusted hazard ratios vs metformin using Cox proportional hazards regression., Results: The ranking of standardized occurrence rates of serious hypoglycemia was glyburide > glimepiride > glipizide > repaglinide > nateglinide > rosiglitazone > pioglitazone > metformin. Rates were increased for all study drugs at higher average daily doses. Adjusted hazard ratios (95% confidence intervals) vs metformin were 3.95 (3.66-4.26) for glyburide, 3.28 (2.98-3.62) for glimepiride, 2.57 (2.38-2.78) for glipizide, 2.03 (1.64-2.52) for repaglinide, 1.21 (0.89-1.66) for nateglinide, 0.90 (0.75-1.07) for rosiglitazone, and 0.80 (0.68-0.93) for pioglitazone., Conclusions: Sulfonylureas were associated with the highest rates of serious hypoglycemia. Among all study drugs, the highest rate was seen with glyburide. Pioglitazone was associated with a lower adjusted hazard for serious hypoglycemia vs metformin, while rosiglitazone and nateglinide had hazards similar to that of metformin., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A 1c (HbA 1c ) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work., Research and Methods: A Steering Committee-comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange-was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees., Results: The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome's short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes-specific development is needed., Conclusions: The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA 1c in the research, development, and evaluation of type 1 diabetes therapies., (© 2017 by the American Diabetes Association.)

Purpose: To characterize hypoglycemia management and identify characteristics associated with refractory (need for additional treatment following initial management) and recurrent (adequate initial treatment followed by blood glucose [BG] ≤50 mg/dL) hypoglycemia., Methods: Retrospective review of adult emergency department (ED) patients who presented to a large academic medical center with hypoglycemia (BG ≤ 50 mg/dL) between January 2011 and July 2015. Data collection focused on BG measurements and treatment practices. Data are reported using descriptive statistics, Wilcoxon rank sum, and χ 2 analysis as appropriate., Results: Two hundred forty-four patients were included (mean age, 59 ± 18.7 years; weight, 85 ± 24.3 kg). Patients arriving via prehospital care (n = 124) were assessed faster in the ED (median, 25 minutes; interquartile range [IQR], 10-40 minutes) compared with ambulatory arrival (median, 43 minutes; IQR, 17-95 minutes; P = .0018). There were 174 patients with a BG ≤ 50 mg/dL in the ED. Of those, 108 (62.1%) were treated with intravascular bolus dextrose/intramuscular glucagon and 21 patients (12%) did not receive any treatment or food. The overall median time to treatment after identification of hypoglycemia was 12 minutes (IQR, 6-27.8 minutes); treatment was administered faster after bedside point-of-care testing assessment compared with when serum samples resulted (11 [IQR, 6-23.5] minutes vs 25 [IQR, 10.75-42.5] minutes, respectively; P = .015). The overall time to repeat BG was obtained 22 (IQR, 8-44) minutes after bolus treatment, but this interval increased with subsequent measurements. Refractory or recurrent hypoglycemia occurred in 30.3% of patients. Mean initial BG was lower in the subset of patients who developed refractory hypoglycemia compared with those who did not (35.1 ± 9.8 vs 37.6 ± 10.2 mg/dL, P = .079), although not statistically significant. Patients with recurrent hypoglycemia were also less likely to receive dextrose containing intravenous fluids compared with those without recurrent hypoglycemia (P = .028). Infection was the only associated characteristic with refractory or recurrent hypoglycemia (P = .021)., Conclusions: Overall, 12% of patients did not receive treatment for hypoglycemia in the ED with a BG ≤ 50 mg/dL. Time to treatment after identification was faster when identified by care testing vs serum sample result. Time to repeat BG in the ED was relatively quick, but did increase over time. About one-third of patients had refractory or recurrent hypoglycemia and infection was associated with this occurrence. Lack of dextrose containing intravenous fluid was associated with the incidence of recurrent hypoglycemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the European Union (EU), the ISO (International Organization for Standardization) 15197 standard is applicable for the evaluation of systems for self-monitoring of blood glucose (SMBG) before the market approval. In 2013, a revised version of this standard was published. Relevant revisions in the analytical performance requirements are the inclusion of the evaluation of influence quantities, for example, hematocrit, and some changes in the testing procedures for measurement precision and system accuracy evaluation, for example, number of test strip lots. Regarding system accuracy evaluation, the most important change is the inclusion of more stringent accuracy criteria. In 2014, the Food and Drug Administration (FDA) in the United States published their own guidance document for the premarket evaluation of SMBG systems with even more stringent system accuracy criteria than stipulated by ISO 15197:2013. The establishment of strict accuracy criteria applicable for the premarket evaluation is a possible approach to further improve the measurement quality of SMBG systems. However, the system accuracy testing procedure is quite complex, and some critical aspects, for example, systematic measurement difference between the reference measurement procedure and a higher-order procedure, may potentially limit the apparent accuracy of a given system. Therefore, the implementation of a harmonized reference measurement procedure for which traceability to standards of higher order is verified through an unbroken, documented chain of calibrations is desirable. In addition, the establishment of regular and standardized post-marketing evaluations of distributed test strip lots should be considered as an approach toward an improved measurement quality of available SMBG systems., (© 2015 Diabetes Technology Society.)

Objective: Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample., Research Design and Methods: Participants ≥18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ≥10, PHQ-8 ≥12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models., Results: A total of 4.6-10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants., Conclusions: In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed., (© 2014 by the American Diabetes Association.)

Objective: To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice., Participants: Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report., Evidence: The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions., Consensus Process: Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012., Conclusions: The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.

Objectives: Hypoglycemia is a common complication of treatment with certain diabetes drugs. Non-severe hypoglycemic events (NSHEs) occur more frequently than severe events and account for the majority of total events. The objective of this multi-country study was to identify how NSHEs in a working population affect productivity, costs, and self-management behaviors., Methods: A 20-minute survey assessing the impact of NSHEs was administered via the Internet to individuals (≥ 18 years of age) with self-reported diabetes in the United States, United Kingdom, Germany, and France. The analysis sample consisted of all respondents who reported an NSHE in the past month. Topics included: reasons for, duration of, and impact of NSHE(s) on productivity and diabetes self-management., Results: A total of 1404 respondents were included in this analysis. Lost productivity was estimated to range from $15.26 to $93.47 (USD) per NSHE, representing 8.3 to 15.9 hours of lost work time per month. Among individuals reporting an NSHE at work (n = 972), 18.3% missed work for an average of 9.9 hours (SD 8.4). Among respondents experiencing an NSHE outside working hours (including nocturnal), 22.7% arrived late for work or missed a full day. Productivity loss was highest for NSHEs occurring during sleep, with an average of 14.7 (SD 11.6) working hours lost. In the week following the NSHE, respondents required an average of 5.6 extra blood glucose test strips. Among respondents using insulin, 25% decreased their insulin dose following the NSHE., Conclusions: NSHEs are associated with substantial economic consequences for employers and patients. Greater attention to treatments that reduce NSHEs could have a major, positive impact on lost work productivity and overall diabetes management., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Self-monitoring blood glucose (SMBG) systems play a critical role in management of diabetes. SMBG systems should at least meet the minimal requirement of the World Health Organization's ISO 15197:2003. For tight glycemic control, a tighter accuracy requirement is needed., Methods: Seven SMBG systems were evaluated for accuracy and precision: Bionime Rightest(™) GM550 (Bionime Corp., Dali City, Taiwan), Accu-Chek(®) Performa (Roche Diagnostics, Indianapolis, IN), OneTouch(®) Ultra(®)2 (LifeScan Inc., Milpitas, CA), MediSense(®) Optium(™) Xceed (Abbott Diabetes Care Inc., Alameda, CA), Medisafe (TERUMO Corp., Tokyo, Japan), Fora(®) TD4227 (Taidac Technology Corp., Wugu Township, Taiwan), and Ascensia Contour(®) (Bayer HealthCare LLC, Mishawaka, IN). The 107 participants (44 men and 63 women) were between 23 and 91 years old. The analytical results of seven SMBG systems were compared with those of plasma analyzed with the hexokinase method (Olympus AU640, Olympus America Inc., Center Valley, PA)., Results: The imprecision of the seven blood glucose meters ranged from 1.1% to 4.7%. Three of the seven blood glucose meters (42.9%) fulfilled the minimum accuracy criteria of ISO 15197:2003. The mean absolute relative error value for each blood glucose meter was calculated and ranged from 6.5% to 12.0%., Conclusions: More than 40% of evaluated SMBG systems meet the minimal accuracy criteria requirement of ISO 15197:2003. However, considering tighter criteria for accuracy of ±15%, only the Bionime Rightest GM550 meets this requirement. Because SMBG systems play a critical role in management of diabetes, manufacturers have to strive to improve accuracy and precision and to ensure the good quality of blood glucose meters and test strips.

Background: Hyperglycemia in the adult inpatient population remains a topic of intense study in U.S. hospitals. Most hospitals have established glycemic control programs but are unable to determine their impact. The 2009 Remote Automated Laboratory System (RALS) Report provides trends in glycemic control over 4 years to 576 U.S. hospitals to support their effort to manage inpatient hyperglycemia., Methods: A proprietary software application feeds de-identified patient point-of-care blood glucose (POC-BG) data from the Medical Automation Systems RALS-Plus data management system to a central server. Analyses include the number of tests and the mean and median BG results for intensive care unit (ICU), non-ICU, and each hospital compared to the aggregate of the other hospitals., Results: More than 175 million BG results were extracted from 2006-2009; 25% were from the ICU. Mean range of BG results for all inpatients in 2006, 2007, 2008, and 2009 was 142.2-201.9, 145.6-201.2, 140.6-205.7, and 140.7-202.4 mg/dl, respectively. The range for ICU patients was 128-226.5, 119.5-219.8, 121.6-226.0, and 121.1-217 mg/dl, respectively. The range for non-ICU patients was 143.4-195.5, 148.6-199.8, 145.2-201.9, and 140.7-203.6 mg/dl, respectively. Hyperglycemia rates of >180 mg/dl in 2008 and 2009 were examined, and hypoglycemia rates of <40 mg/dl (severe) and <70 mg/dl (moderate) in both 2008 and 2009 were calculated., Conclusions: From these data, hospitals can determine the current state of glycemic control in their hospital and in comparison to other hospitals. For many, glycemic control has improved. Automated POC-BG data management software can assist in this effort., (© 2010 Diabetes Technology Society.)

Purpose: To determine the (1) incidence of peripheral blood glucose (PBG < 40 mg/dL) in infants within 2 hours of birth and (2) validity of using maternal and infant risk factors and/or infant signs/symptoms of hypoglycemia as a screen for PBG < 40 mg/dL., Study Design: Descriptive study with a convenience sample of 220 mother-infant dyads admitted to a mother-baby unit. Maternal and infant risk factors and infant signs/symptoms of hypoglycemia were assessed, and a PBG value was obtained within 2 hours of birth from the infant. Data were analyzed with descriptive statistics, multiple regression analysis, and sensitivity and specificity testing., Results: The incidence of PBG < 40 mg/dL was 5.1% (N = 10 of 198). Fifteen maternal/infant risk factors were found; 2 of the 23 risk factors predicted PBG values within 2 hours of birth at a statistically significant level (jitteriness [p = .011] and tachypnea [p = .033]). Sensitivity was 71.9% and specificity 44.7% for using the presence of at least one maternal/infant risk factor and/or infant signs/symptoms of hypoglycemia to correctly identify PBG < 40 mg/dL within 2 hours of birth., Clinical Implications: Nurses working with mothers and infants can use the data from our study along with the recommendations from professional organizations such as American Academy of Pediatrics to begin a conversation at their institutions about revising protocols for routine PBG testing. Screening infants for maternal/infant risk factors and infant signs/symptoms of hypoglycemia could be used instead to safely decrease by 45% the number of infants who would need to have a PBG sample obtained within 2 hours of birth.

The prehospital providers in this case performed a thorough and detailed assessment. They searched for and found a puncture wound in the posterior buccal region, and learned the patients was also hypoglycemic, with a history of diabetes, and insulin-dependent. It was not clear how the patient arrived at a hypoglycemic state, or if he had suffered a seizure. After the family arrived at the hospital and went to the patient's home, they determined the circumstances that caused this unusual presentation: The patient was the victim of a home-invasion robbery and had been shot in the mouth with a small-caliber weapon. The home invasion had taken place approximately 12 hours prior to the victim being found. The victim had been knocked unconscious by the force of the shot, although the bullet did not break any bones. He had not eaten prior to the shooting. Upon arrival at the ED, a small exit wound was noted behind the patient's left ear--hair and dried blood had obscured it from the prehospital providers. However, the providers did alert the ED physician to the buccal puncture wound, which enabled the physician to consider the possibility that the mouth wound was the result of a gunshot. Gunshot wounds are unpredictable in their damage patterns and effects on their victims. They might lead a patient to become hemodynamically unstable, but that was not the case here. Hemodynamic stability should not preclude the consideration of traumatic insult throughout your assessment. The initial presentation of this patient may have tempted EMS to pursue the suspicions stated by the neighbor at the scene (seizure), but a detailed assessment provided the information necessary to treat the man appropriately.

Background: Out-of-hospital (OOH) emergency personnel measure serum glucose in order to determine the need for dextrose therapy. Most devices that measure serum glucose are designed to use capillary blood obtained from a finger puncture. However, OOH emergency personnel often use venous blood obtained during intravenous line (IV) placement to determine serum glucose., Objective: To compare capillary and venous glucose measurements., Methods: This prospective study used healthy, non-fasting volunteers. Simultaneous venous and capillary blood samples were obtained from each subject. Glucose levels were measured using a glucometer designed for capillary samples. The capillary and venous measurements were compared using a Pearson correlation coefficient. Power analysis revealed that the study had the ability to detect a difference of 15 mg/dL., Results: Ninety-seven volunteers (56 males, 41 females) with a mean age of 37 +/- 11.9 years were enrolled. The mean capillary and venous glucose values were 104.5 +/- 20.7 mg/dL and 109.7 +/- 22.4 mg/dL, respectively. The Pearson correlation coefficient was 0.24., Conclusions: The correlation between venous and capillary blood glucose measurements is relatively poor in this group of healthy volunteers. Further research must be conducted on patients at risk for abnormal blood glucose.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macrosomia, macroglossia, abdominal wall defects, hypoglycemia in the neonatal period and embryonal cancers of infancy and early childhood. The frequency of hypoglycemia in this population is between 30% and 50%. The majority of infants with hypoglycemia will be asymptomatic and have resolution of the hypoglycemia within the first 3 days of life. Less than 5% will have hypoglycemia beyond the neonatal period requiring either continuous feeding or a partial pancreatectomy. The cause of hypoglycemia is unclear, but direct and indirect evidence supports a hyperinsulinemia as the major factor. Recent identification of the majority of genes associated with BWS in the 11p15 region and the genotype of persistent hyperinsulinemia hypoglycemia of childhood also in the 11p15 region may provide a molecular basis for hypoglycemia in BWS, particularly for the occasional patients with hypoglycemia requiring a partial pancreatectomy. Detailed genotype phenotype evaluations are needed and should provide an insight as to why patients with BWS have hypoglycemia.