Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

<i>Objective:</i> This study aims to: (1) identify the frequency of severe and level 2 hypoglycemia presenting in people with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting; (2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. <p><i>Research Design and Methods:</i> A cross-sectional survey study in adults with type 1 diabetes using CGMs >6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire) and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors. </p> <p><i>Results: </i>A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (<i>P</i><0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (<i>P</i>=0.038).</p> <p><i>Conclusions:</i> Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in people with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may remain to impact the effectiveness of glucose self-management.</p>

Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

<i>Objective:</i> This study aims to: (1) identify the frequency of severe and level 2 hypoglycemia presenting in people with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting; (2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. <p><i>Research Design and Methods:</i> A cross-sectional survey study in adults with type 1 diabetes using CGMs >6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire) and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors. </p> <p><i>Results: </i>A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (<i>P</i><0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (<i>P</i>=0.038).</p> <p><i>Conclusions:</i> Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in people with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may remain to impact the effectiveness of glucose self-management.</p>

Beliefs Around Hypoglycemia and Their Impacts on Hypoglycemia Outcomes in Individuals with Type 1 Diabetes and High Risks for Hypoglycemia Despite Using Advanced Diabetes Technologies

OBJECTIVE This study aimed to 1) identify the frequency of severe and level 2 hypoglycemia presenting in individuals with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those with concomitant closed-loop insulin pumps, in a clinical practice setting, and; 2) evaluate the impact of beliefs around hypoglycemia in the development of severe and level 2 hypoglycemia in this population. RESEARCH DESIGN AND METHODS A cross-sectional survey study in adults with type 1 diabetes using CGMs &gt;6 months was conducted at a large tertiary academic center. Participant demographics, 6-month severe hypoglycemia history, hypoglycemia beliefs (with the Attitude to Awareness of Hypoglycemia questionnaire), and 4-week CGM glucose data were collected. Statistical analysis was performed to assess the presentation of severe and level 2 hypoglycemia and identify associated risk factors. RESULTS A total of 289 participants were recruited (including 257 participants with CGM data within the last 3 months). Of these, 25.6% experienced at least one severe hypoglycemic episode in the last 6 months, and 13.6% presented with ≥1% of time in level 2 hypoglycemia on CGMs. Reporting beliefs about prioritizing hyperglycemia avoidance was associated with severe hypoglycemia development (P &lt; 0.001), while having beliefs of minimal concerns for hypoglycemia was associated with spending ≥1% of time in level 2 hypoglycemia (P = 0.038). CONCLUSIONS Despite the use of advanced diabetes technologies, severe and level 2 hypoglycemia continues to occur in individuals with type 1 diabetes and high hypoglycemia risks. Human factors, including beliefs around hypoglycemia, may continue to impact the effectiveness of glucose self-management.

A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia

Background Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. In vitro analyses suggest a longer release of glucose when using sweet manioc starch (SMS). Methods We compared the efficacy and safety of the administration of SMS and UCCS during a short-fasting challenge in patients with GSD Ia in a randomized, triple-blind, phase I/II, cross-over study. GSD Ia patients aged ≥ 16 years and treated with UCCS were enrolled. Participants were hospitalized for two consecutive nights, receiving UCCS or SMS in each night. After the administration of the starches, glucose, lactate and insulin levels were measured in 1-h interval throughout the hospitalization period. The procedures were interrupted after 10 h of fasting or in a hypoglycemic episode (< 3.88 mmol/L). Results Eleven individuals (mean age: 21.6 ± 4.3 years; all presenting body mass index > 25 kg/m2) participated in the study. The average fasting period was 8.2 ± 2.0 h for SMS and 7.7 ± 2.3 h for UCCS (p = 0.04). SMS maintained euglycemia for a greater period over UCCS. Increased lactate concentrations were detected even in absence of hypoglycemia, not being influenced by the different starches investigated (p = 0.17). No significant difference was found in total cholesterol, HDL, triglycerides and uric acid levels in both arms. None of the patients showed severe adverse events. Conclusions SMS appears to be non-inferior to UCCS in the maintenance of euglycemia, thus emerging as a promising alternative to the treatment of GSD Ia.

Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure

Background Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF. Methods To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2. Results Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P &lt; 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006). Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2. Conclusions Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.

Congenital Hyperinsulinism Due to a Novel Activating Glucokinase Mutation: A Case Report and Literature Review

Background: Congenital Hyperinsulinism (CHI) constitutes a major cause of persistent and recurrent hypoglycemia, especially in the neonatal period, showing notable phenotypical heterogeneity among affected subjects. Activating mutations of the Glucokinase gene (GCK) are responsible for mild forms of hypoglycemia, due to CHI, usually easily medically managed. Case report: We present a patient at the age of 3.5 years old investigated for persistent hypoglycemia. Laboratory evaluation showed hyperinsulinism during the hypoglycemic episode with a required glucose infusion rate greater than 8-10 mg/kg/min to maintain normoglycemia. Targeted gene panel sequencing revealed an activating missense novel mutation p.Val71Ala in exon 3 of GCK gene, dominantly inherited by his mother. In silico, analysis of this novel missense variant assessed its pathogenicity as being of uncertain significance Conclusions: GCK gene mutations result in varying phenotypic characteristics and responsiveness to diazoxide depending on the type of activating mutation.

Glucose Variations in the First Day of Life of Newborns under Observational Surveillance

Purpose: Nursing protocols for glucose management are well known for both healthy term newborns and high-risk newborns. However, for less risky newborns who are under only observation surveillance, hypoglycemia could be overlooked unless clinical symptoms develop. Methods: A retrospective study was performed to explore factors influencing variations in glucose levels in 91 newborns who did not require any interventions, but were under nursing surveillance, at a level II neonatal intensive care unit. Data were retrieved from electrical medical records on glucose levels, demographic characteristics, and other clinical characteristics of newborns in their first day of life from January 2016 to May 2019. Results: Glucose levels tended to stabilize within the normal range (60~80 mg/dL) as time passed during the first day of life. Cesarean section, multiple gestation, abnormal growth, and later preterm birth were associated with low glucose levels in the first 2 hours of life. Thirty-one newborns experienced a hypoglycemic episode (< 45 mg/dL) during the first 24 hours of life. Conclusion: The findings of this study support the active encouragement of early feeding within 2 hours of birth and urgent adoption of a structural protocol for glucose surveillance in newborns with potential health problems immediately after birth.

MON-620 Ademolus Hypoglycemic Index

This article proposes ADEMOLUS HYPOGLYCEMIC INDEX (AHI) which is a mathematical representation of hypoglycemic episode (HE) in a patient with recurrent hypoglycemia over a consecutive three months period. It also apply it to clinical practice using diabetic patients in order to demonstrate and emphasize its relevance in present day medical practice worldwide. This is a retrospective study of 65 HE occurring in 6 randomly selected diabetes mellitus patients from 86 case files studied who had attended the endocrinology unit. The data was analyzed by using Ademolus Classification of hypoglycemia (ACH) and the 2018 ADA/EASD Classification of hypoglycemia to define hypoglycemia. AHI was calculated from the HE using the proposed mathematical formula. SPSS version 23 was used for data analysis. All six patients had a series of hypoglycemic episodes occurring in three consecutive months. Patient 1 had an AHI of 0.53 using both ACH and 2018 ADA/EASD classification.By using the Pearson correlation statistics, AHI using ACH correlated well with AHI using 2018 ADA/EASD classification of hypoglycemia with a value of 0.993.Similarly the findings of AHI derived using ACH is significant with values derived using ADA/EASD 2018 classification of hypoglycemia with a p-value of 0.000 (correlation is significant at values of 0.01). One of the clinical implication of AHI is that the risk of developing reversible or irreversible neurological damage can be reduced clinically as patient with mild to moderate form of chronic hypoglycemia yet to develop irreversible neurological damage or neurological sequelae can be prevented early enough from progressing since a reduced AHI value out of a series will be a pointer towards progression to neurological damage if it has not occurred! In patient 1 her AHI was not in the severe range. In patient 3, in the last quarter of 2016, her AHI was 0.60, in the first quarter of 2017, her AHI was zero, then between June, July and August 2017 her AHI was 0.64. At this juncture in this patient management, it will be good to evaluate the etiological factors in this chronic kidney disease diabetic patient who once again has started having recurrent hypoglycemia as it was some 6 months earlier. Patient 6 had two consecutive reading of AHI for two consecutive quarters of a year.The result reveals that she is chronically deteriorating gradually and tending towards more severity in her development of HE as her AHI fell from 0.52 in the preceding quarter to 0.46., this connotes worsening chronic hypoglycemic state over time and a poorer prognosis. The lower the AHI, the poorer the prognosis.AHI is relevant for monitoring of chronic or long term recurrent HE in susceptible individuals whether diabetic or not. References: 1. Fonseca VA, Kirkman MS, Darsow T, Ratner RE (2012) The American Diabetes Association Diabetes Research Perspective. Diabetes Care 35(6): 1380–1387.

Improving interpretability of individual Diabetes Symptom Checklist-Revised (DSC-R) scores: the role of patient characteristics

IntroductionThe Diabetes Symptom Checklist-Revised (DSC-R) is a well-validated patient-reported outcome designed to assess symptom burden in persons with type 2 diabetes mellitus (T2DM) across eight domains. The DSC-R has so far primarily been used in research settings. With the aim to make the DSC-R applicable in clinical practice by improving its interpretability, we sought to identify patient characteristics associated with DSC-R (domain) scores as a first initiative toward reference values.Research design and methodsWe used baseline data from two large observational studies to select patient characteristics significantly associated with DSC-R domain and total scores. Multivariable Tobit analyses with the backward procedure per (domain) score were performed.ResultsData from 1531 participants with T2DM were included. On a 0–100 scale, the median DSC-R total score was 15.88 (7.06–29.41), with domain scores ranging from 5.00 (0.00–22.50) (pain) to 35.00 (10.00–60.00) (fatigue). Low well-being status was most profoundly associated with higher scores across all domains. Persons with one or more complication, as well as one or more symptomatic hypoglycemic episode during the past 3 months, scored higher on (almost) all domains and the total scale.ConclusionsComplications, symptomatic hypoglycemia, and low well-being are important characteristics to take into account when using the DSC-R in individual patients. Further validation of our findings is warranted in diverse patient populations.

10 Hypoglycemic Episodes Predict Length of Stay in Patients with Acute Burns

Introduction Hypoglycemic episodes are associated with worse hospital outcomes, and their incidence varies by institution. We sought to define the prevalence of hypoglycemic episodes at our burn center and determine their association with hospital outcomes. Methods We retrospectively reviewed all consecutive adult and pediatric patients admitted to our burn center from 2015 to 2019. Patient demographics and burn characteristics were recorded. The primary outcome was mortality, and secondary outcomes were total length of stay (LOS) and intensive care unit LOS (ICU LOS). All patients experiencing hypoglycemic episodes were compared to patients who did not experience hypoglycemic episodes (controls) using two-tailed t, chi-squared, and multivariate logistic and multiple linear regression analyses. Results A total of 914 patients with acute burns were admitted during the study period. Thirty-three patients (4%) experienced hypoglycemic episodes (&lt; 60 mg/dL). Of these, 17 patients (52%) experienced a single hypoglycemic episode, while the remainder (N=16) experienced multiple hypoglycemic episodes. There were no significant differences in age, sex, or presence of inhalation injury between hypoglycemic patients and controls. Patients that experienced a hypoglycemic episode had significantly greater TBSA involvement (23% vs. 11%, p&lt; 0.00), higher prevalence of diabetes (48% vs. 20%, p&lt; 0.00), higher mortality (18% vs. 7%, p=0.01), longer total LOS (39 vs. 13 days, p&lt; 0.00), and longer ICU LOS (28 vs. 4 days, p&lt; 0.00). A single hypoglycemic episode was associated with prolonging total LOS by 19 days (p&lt; 0.00) and ICU LOS by 18 days (p&lt; 0.00). Hypoglycemic episodes were not associated with higher odds of mortality (OR=0.9, 95% CI 0.3–3.0, p &gt;0.05). There were no differences in outcomes between patients with single or multiple hypoglycemic episodes. Patients with multiple hypoglycemic episodes more frequently had a history of diabetes (81% vs. 18%, p&lt; 0.00), and worse glucose control (HbA1c, 9% vs. 7%, p=0.04) compared to patients with single episodes. Conclusions Hypoglycemic episodes were associated with longer total and ICU LOS in our study but did not portend higher mortality. Applicability of Research to Practice Quality improvement efforts to prevent hypoglycemic episodes should focus efforts on known diabetics with high HbA1c levels.