Hypoglycemia Changes Research Articles

Continuous Glucose Monitoring With Geriatric Principles in Older Adults With Type 1 Diabetes and Hypoglycemia: A Randomized Controlled Trial.

Continuous glucose monitoring (CGM) use in older adults with type 1 diabetes (T1D) has shown benefits. However, the impact of CGM use, coupled with simplified treatment regimens and personalized glycemic goals that are better suited for older patients with multiple comorbidities and hypoglycemia, is not known. Older adults (≥65 years) with T1D with hypoglycemia (two or more episodes of hypoglycemia [blood glucose <70 mg/dL for ≥20 min over 2 weeks]) who were CGM naïve or CGM users were randomized to intervention and control groups. The intervention consisted of the combined use of CGM with geriatric principles (i.e., adjusting goals based on overall health, and simplification of regimens based on CGM patterns and clinical characteristics) over 6 months. The control group received usual care by their endocrinologist. The primary end point was change in time when blood glucose was <70 mg/dL from baseline to 6 months. Cost-effectiveness was calculated using a health care sector perspective. We randomized 131 participants (aged 71 ± 5 years; 21% ≥75 years old) to the intervention (n = 68; CGM users = 33) or the control (n = 63; CGM users = 40) group. The median change in hypoglycemia from baseline to 6 months was -2·6% in the intervention group and -0.3% in the control group (median difference, -2.3% [95% CI -3.7%, -1.3%]; P < 0.001). This improvement was seen in both CGM naïve (-2.8%; 95% CI -5.6%, -0.8%) and CGM users (-1.2%; 95% CI -2.7%, -0.1%). The HbA1c did not differ between the groups (7.5% vs 7.3%). The intervention was cost-effective (incremental cost-effectiveness ratio $71,623 per quality adjusted life-year). In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion.

Safety and tolerability of a low glycemic load dietary intervention in adults with cystic fibrosis: a pilot study.

To achieve and maintain adequate weight, people with cystic fibrosis (CF) May often consume energy-dense, nutrient-poor foods high in added sugars and refined carbohydrates; however, little is known about the glycemic and metabolic effects of dietary composition in this patient population. The objective of this pilot study was to investigate the safety and tolerability of a low glycemic load (LGL) diet in adults with CF and abnormal glucose tolerance (AGT). Ten adults with CF and AGT completed this prospective, open-label pilot study. Mean age was 27.0 ± 2.1 years, 64% were female, and all had pancreatic insufficiency. Each participant followed his/her typical diet for 2 weeks, then transitioned to a LGL diet via meal delivery service for 8 weeks. The primary outcome was change in weight from baseline to study completion, with safety established if no significant decline was noted. Other key safety outcomes included change in hypoglycemia measured by patient report and continuous glucose monitoring (CGM). Exploratory outcomes included changes in other CGM measures, body composition by dual energy X-ray absorptiometry (DXA), and patient reported outcomes. There were no significant changes in weight or in subjectively-reported or objectively-measured hypoglycemia. Favorable non-significant changes were noted in CGM measures of hyperglycemia and glycemic variability, DXA measures of fat mass, and gastrointestinal symptom surveys. A LGL dietary intervention was safe and well tolerated in adults with CF and AGT. These results lay the groundwork for future trials investigating the impact of low-glycemic dietary interventions on metabolic outcomes in the CF population.

1125-P: Real-World Pediatric Outcomes of Hybrid Closed-Loop Systems at a Large Urban Center

Objectives: To study the real-world effect of hybrid closed loop systems (HCLS) on glycemic control and quality of life (QoL) in pediatric patients with T1D. Methods: Patients 2-20 years old with T1D for ≥ 1 year were recruited when starting t:slim x2 with CIQ (TS) or Omnipod 5 (O5). We collected time in range (TIR), time low (BG &amp;lt;70 mg/dl), A1c, and QoL survey responses at baseline and 3 months. Kruskal-Wallis rank sum test and chi-squared test were used for data analysis. Results: Baseline data is in Figure 1. TIR improved by 7% after 3 months of HCLS use (p=0.004). Time low was unchanged after 3 months (p=0.3). Figure 2 shows results by subject. Discussion: In this real-world study, HCLS improved TIR at 3 months without change in hypoglycemia. Data collection, enrollment, and analysis are ongoing with more results (A1c, QoL surveys) expected shortly. Disclosure C.V. Tillotson: None. P.H. Nichols: None. K. Mofford: None. N. Leibel: None. R. Gandica: None. Funding National Institutes of Health (5T32DK065522-18)

59-OR: Glycemic Control with Extended Use of Automated Insulin Delivery (AID) in Children Age 2–6 Years with Type 1 Diabetes (T1D)

T1D management in children &amp;lt; age 6 yrs is challenging due to unpredictable food intake and activity. Efficacy of AID with the Tandem t:slim X2 insulin pump with Control-IQ technology (CIQ) in this age group has not been well studied. Data included 95 children with T1D age 2 to &amp;lt; 6 yrs (age 3.9±1.2 yrs, 46% male, 75 % non-Hispanic white, 34% on multiple daily injections) enrolled in a 13-week extended use phase of a randomized trial of closed loop control (CLC) with CIQ. In this phase, the group assigned to CLC for the initial 13 weeks continued on CLC (CLC-CLC) and those initially using standard care (SC) were placed on CLC (SC-CLC). CGM time in range 70-180 mg/dL (TIR) was the primary outcome. The SC-CLC group (n=33) increased TIR using CLC in the extension compared to the SC period (68±9% vs. 56±13%, p&amp;lt;0.001) with no significant change in hypoglycemia (%CGM &amp;lt; 54 mg/dL 0.4±0.3% vs. 0.5±0.6%, p=0.03). TIR increased within the first week of CLC use similar to the first 13 weeks of AID use for the CLC-CLC group (Figure). CLC training was completed virtually for 82% of the SC-CLC group. The CLC-CLC group (n=62) maintained TIR (71±11% vs. 70±10%, p=0.80) with slightly lower rates of hypoglycemia (%CGM &amp;lt; 54 mg/dL 0.5±0.4% vs. 0.6±0.5%, p=0.08). In conclusion, these data show that in young children age 2 to &amp;lt; 6, CLC with Control-IQ technology leads to increased TIR without an increase in time in hypoglycemia. Disclosure R.Wadwa: Consultant; Eli Lilly and Company, Other Relationship; Dexcom, Inc., Eli Lilly and Company, Research Support; Dexcom, Inc., Eli Lilly and Company, Beta Bionics, Inc., Tandem Diabetes Care, Inc. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. M.D.Breton: Consultant; Dexcom, Inc., Tandem Diabetes Care, Inc., Roche Diabetes Care, Sanofi, Arecor, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Novo Nordisk. Pedap trial study group: n/a. Z.Reed: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. M.D.Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. E.C.Cobry: None. M.Schoelwer: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation. C.Berget: Consultant; Insulet Corporation, Dexcom, Inc., Other Relationship; Tandem Diabetes Care, Inc. J.W.Lum: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127551); Tandem Diabetes Care, Inc.; Dexcom, Inc.

Use of Telecommunication and Diabetes-Related Technologies in Older Adults With Type 1 Diabetes During a Time of Sudden Isolation: Mixed Methods Study.

The COVID-19 lockdown imposed a sudden change in lifestyle with self-isolation and a rapid shift to the use of technology to maintain clinical care and social connections. In this mixed methods study, we explored the impact of isolation during the lockdown on the use of technology in older adults with type 1 diabetes (T1D). Older adults (aged ≥65 years) with T1D using continuous glucose monitoring (CGM) participated in semistructured interviews during the COVID-19 lockdown. A multidisciplinary team coded the interviews. In addition, CGM metrics from a subgroup of participants were collected before and during the lockdown. We evaluated 34 participants (mean age 71, SD 5 years). Three themes related to technology use emerged from the thematic analysis regarding the impact of isolation on (1) insulin pump and CGM use to manage diabetes, including timely access to supplies, and changing Medicare eligibility regulations; (2) technology use for social interaction; and (3) telehealth use to maintain medical care. The CGM data from a subgroup (19/34, 56%; mean age 74, SD 5 years) showed an increase in time in range (mean 57%, SD 17% vs mean 63%, SD 15%; P=.001), a decrease in hyperglycemia (>180 mg/dL; mean 41%, SD 19% vs mean 35%, SD 17%; P<.001), and no change in hypoglycemia (<70 mg/dL; median 0.7%, IQR 0%-2% vs median 1.1%, IQR 0%-4%; P=.40) during the lockdown compared to before the lockdown. These findings show that our cohort of older adults successfully used technology during isolation. Participants provided the positive and negative perceptions of technology use. Clinicians can benefit from our findings by identifying barriers to technology use during times of isolation and developing strategies to overcome these barriers.

Fear of hypoglycemia changes nutritional factors and behavioral strategies before the exercise in patients with type 1 diabetes mellitus

Fear of hypoglycemia changes nutritional factors and behavioral strategies before the exercise in patients with type 1 diabetes mellitus

Metabolic Control of the FreeStyle Libre System in the Pediatric Population with Type 1 Diabetes Dependent on Sensor Adherence

Aims: To evaluate the relationship between daily sensor scan rates and changes in HbA1c and hypoglycemia in children. Methods: We enrolled 145 paediatric T1D patients into a prospective, interventional study of the impact of the FreeStyle Libre 1 system on measures of glycemic control. Results: HbA1c was higher at lower scan rates, and decreased as the scan rate increased to 15–20 scans, after which it rose at higher scan rates. An analysis of the change in hypoglycemia, based on the number of daily sensor scans, showed there was a significant correlation between daily scan rates and hypoglycemia. Subjects with higher daily scan rates reduced all levels of hypoglycaemia. Conclusions: HbA1c is higher at lower scan rates, and decreases as scan rate increases. Reductions in hypoglycemia were evident in subjects with higher daily scan rates.

HYPO-CHEAT's aggregated weekly visualisations of risk reduce real world hypoglycaemia.

BackgroundChildren with congenital hyperinsulinism (CHI) are at constant risk of hypoglycaemia with the attendant risk of brain injury. Current hypoglycaemia prevention methods centre on the prediction of a continuous glucose variable using machine learning (ML) processing of continuous glucose monitoring (CGM). This approach ignores repetitive and predictable behavioural factors and is dependent upon ongoing CGM. Thus, there has been very limited success in reducing real-world hypoglycaemia with a ML approach in any condition.ObjectivesWe describe the development of HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-CGM-HEatmap-Technology), which is designed to overcome these limitations by describing weekly hypoglycaemia risk. We tested HYPO-CHEAT in a real-world setting to evaluate change in hypoglycaemia.MethodsHYPO-CHEAT aggregates individual CGM data to identify weekly hypoglycaemia patterns. These are visualised via a hypoglycaemia heatmap along with actionable interpretations and targets. The algorithm is iterative and reacts to anticipated changing patterns of hypoglycaemia. HYPO-CHEAT was compared with Dexcom Clarity's pattern identification and Facebook Prophet's forecasting algorithm using data from 10 children with CHI using CGM for 12 weeks. HYPO-CHEAT's efficacy was assessed via change in time below range (TBR).ResultsHYPO-CHEAT identified hypoglycaemia patterns in all patients. Dexcom Clarity identified no patterns. Predictions from Facebook Prophet were inconsistent and difficult to interpret. Importantly, the patterns identified by HYPO-CHEAT matched the lived experience of all patients, generating new and actionable understanding of the cause of hypos. This facilitated patients to significantly reduce their time in hypoglycaemia from 7.1% to 5.4% even when real-time CGM data was removed.ConclusionsHYPO-CHEAT's personalised hypoglycaemia heatmaps reduced total and targeted TBR even when CGM was reblinded. HYPO-CHEAT offers a highly effective and immediately available personalised approach to prevent hypoglycaemia and empower patients to self-care.

The impact of “faster aspart” on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump

Background and aimsPost-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new “faster aspart” insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of “faster aspart” vs. “insulin aspart” in children and adolescents with DM1 on sensor-augmented pump treatment. Patients and methodsMulticentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) <70 and >180 mg/dL, mean sensor glucose pre- and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. ResultsThe study included 32 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia >180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = .011) and >250 mg/dL (5.2±4.9 vs. 4.0 ± 3.6; p = .04), lower AUC >180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = .03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = .03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. ConclusionsFaster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

Attenuated Induction of the Unfolded Protein Response in Adult Human Primary Astrocytes in Response to Recurrent Low Glucose.

Aims/hypothesisRecurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure.MethodsHuman primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq, respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform.Results24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such as HSPA5, XBP1, and MANF, involved in the unfolded protein response (UPR), were all significantly increased following low glucose (LG) exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures.Conclusions/interpretationThese data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be a consequence of a successful metabolic adaptation, as previously reported, that better preserves intracellular energy levels and a reduced necessity for the UPR.

Impacto de faster aspart sobre el control glucémico en niños y adolescentes con diabetes tipo 1 en tratamiento con un sistema integrado

Background and aimsPost-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new «faster aspart» insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of «faster aspart» vs. «insulin aspart» in children and adolescents with DM1 on sensor-augmented pump treatment. Patients and methodsMulticentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) < 70 and > 180 mg/dL, mean sensor glucose pre and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. ResultsThe study included 31 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia > 180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = 0.011) and > 250 mg/dL (5.2 ± 4.9 vs. 4.0 ± 3.6; p = 0.04), lower AUC > 180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = 0.03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = 0.03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. ConclusionsFaster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

Hypoglycemia increases endothelial-dependent vasodilation through suppressing phosphorylation at Threonine 495/497 site of endothelial nitric oxide synthase

ObjectivePhosphorylation plays an essential role in the regulation of endothelial nitric oxide synthase (eNOS) activity. However, the phosphorylation of eNOS under hypoglycemia and whether hypoglycemia changes eNOS activity is unknown. This paper aims to clarify the regulation of eNOS phosphorylation and its activity change under hypoglycemia. MethodsBovine aortic endothelial cells (BAECs) and Sprague-Dawley rats were treated with hypoglycemia, and the phosphorylation of eNOS was subjected to western blot. Blood nitric oxide (NO) concentration was determined by NO kit and endothelial-dependent vasodilation was detected by multi-wire myograph. ResultsIn both BAECs and rats' thoracic aorta, hypoglycemia induced eNOS phosphorylation decrease specifically on Threonine (Thr) 497. Inhibition of ubiquitination of protein kinase C α subunit (PKCα) reverses the decrease of eNOS phosphorylation in hypoglycemia. Ubiquitinated PKCα can be reversed by AMPK knockdown. In rats, insulin induced hypoglycemia increased the concentration of NO in arterial blood, and progressively enhanced the endothelium-dependent vasodilation of the thoracic and mesenteric aorta. ConclusionsIn vitro, the activation of AMPK may lead to the expression of PKCα by regulating ubiquitination, resulting in a decrease in the level of P-eNOS Thr497 phosphorylation under hypoglycemia. In vivo, insulin-induced hypoglycemia produces a beneficial cardiovascular effect on rats.

202-OR: Basal Insulin Digital Titration App vs. Enhanced Paper Titration Tool: A Randomized Control Study

Self-adjusting insulin is challenging for people with type 2 diabetes (PWT2D). Mobile health technologies (mHealth) can help PWT2D track blood glucose more easily, but it remains unclear whether an mHealth-enabled digital therapeutic tool can effectively support basal insulin (BI) titration in a large multispecialty health care setting. We randomized 242 PWT2D on BI (baseline HbA1c 7.5% - 12.5%) to use either an app-based self-titration tool [Mobile Insulin Dosing System (MIDS)] or an enhanced paper titration tool based on a stepped algorithm with diabetes educator support (control) for 16 weeks. Cohort characteristics for the intent to treat sample (MIDS n = 117; control n = 120) were: median age 61 years [IQR: 53 - 69], 41.7% female, 75.9% non-Hispanic White, 11.4% new to insulin, median duration of diabetes 11 years [IQR: 7 - 18], and median baseline HbA1c of 8.7% [IQR: 8.0 - 9.6]. Improvements in HbA1c (-1.3% [IQR: -2.2 - -.5] and -1.2% [IQR: -1.9 - -.5]; both Ps &amp;lt; .05) with increased median insulin dose (+8 IU [IQR: 2 - 22] and +10 IU [IQR: 2 - 25.5]; both Ps &amp;lt; .05) and no change in hypoglycemia were observed at 16 weeks in both the MIDS and control groups, respectively. No differences in HbA1c (P = .48) or insulin dose change (P = .34) were observed between the groups. Among SMBG readings recorded during the study, the mean proportion of readings between 70-180 mg/dL (76.8% ± 22.0; 70.0% ± 26.7; p&amp;lt;0.05) and &amp;gt;250 mg/dL (4.9% ± 9.2; 9.2% ± 18.4; p&amp;lt;0.05) both favored the MIDS group. The use of MIDS and the enhanced paper-based tool for BI self-titration both resulted in higher insulin dose and significantly improved glycemic control among PWT2D who were relatively uncontrolled despite most already being treated with insulin. An mHealth-enabled digital therapeutic tool such as MIDS may offer an effective alternative option for PWT2D and their HCPs for titrating BI to non-mHealth approaches; future RCTs will more clearly elucidate the efficacy of MIDS compared to usual care. Disclosure A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. A.L. Fortmann: None. A. Bastian: None. A. Kanchi: Employee; Self; Glooko, Inc. Stock/Shareholder; Self; Glooko, Inc. R. Abad: Employee; Self; Glooko, Inc. T. Sheng: Employee; Self; Glooko, Inc. L. Parks: Employee; Self; Glooko, Inc. M. Greenfield: Consultant; Self; Glooko, Inc. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc.

23-OR: EHR-Based Blood Glucose Alerts Improve Inpatient Glycemic Control at a Large Academic Medical Center

Hospital blood glucose (BG) management is a challenge. We implemented an electronic health record (EHR)-based system at our 1541-bed academic medical center (AMC), alerting when a patient (pt) experiences significant hyperglycemia (hyper; 2 BGs ≥300 mg/dL over 48 hours) or hypoglycemia (hypo; &amp;lt;70 mg/dL). These Excursion Event Alerts (EEAs) fired to the clinician entering orders and provided links to insulin order sets and consult requests. The EEAs were launched on 14 non-ICU wards in mid-2019. We compared BG control during the 3 months prior to launch vs. the most recent 3 months. The control group consisted of 12 non-EEA wards. Our 1° outcome was the Quality Hyperglycemia Score-2 (QHS2), previously developed to assess/compare the overall BG quality on individual wards. QHS2 (scale, 0-100) incorporates 5 elements of BG management, crediting overall control as well as the minimization of significant fluctuations. After the intervention, there was a substantial 13.8% improvement in mean QHS2 (+9.36, p=0.029), comprised of more pt-days in target (+4.3%, p=0.024) and a trend for less pt-days with severe hyper (-2%, p=0.09), with no change in hypoglycemia. In contrast, there was no change in QHS2 on control wards. We conclude that a glycemic alert system was associated with improved BG control at our large AMC, suggesting that a simple EHR-based intervention can favorably impact hospital diabetes management. Disclosure L.B. Bak: None. T.M. Fandel: None. J.E. Bozzo: None. M.L. DeWitt: None. P. Chen: None. R.A. Pando: None. L. Ferro: None. R. Kaplan: None. K.C. Hendrickson: None. S.B. Amport: None. L. Sussman: None. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck &amp; Co., Inc., vTv Therapeutics.

Marked improvement in HbA1c following commencement of flash glucose monitoring in people with type 1 diabetes

Aims/hypothesisMinimal evidence supports the efficacy of flash monitoring in lowering HbA1c. We sought to assess the impact of introducing flash monitoring in our centre.MethodsWe undertook a prospective observational study to assess change in HbA1c in 900 individuals with type 1 diabetes following flash monitoring (comparator group of 518 with no flash monitoring). Secondary outcomes included changes in hypoglycaemia, quality of life, flash monitoring data and hospital admissions.ResultsThose with baseline HbA1c ≥58 mmol/mol (7.5%) achieved a median −7 mmol/mol (interquartile range [IQR] −13 to −1) (0.6% [−1.2 to −0.1]%) change in HbA1c (p < 0.001). The percentage achieving HbA1c <58 mmol/mol rose from 34.2% to 50.9% (p < 0.001). Median follow-up was 245 days (IQR 182 to 330). Individuals not using flash monitoring experienced no change in HbA1c across a similar timescale (p = 0.508). Higher HbA1c (p < 0.001), younger age at diagnosis (p = 0.003) and lower social deprivation (p = 0.024) were independently associated with an HbA1c fall of ≥5 mmol/mol (0.5%). More symptomatic (OR 1.9, p < 0.001) and asymptomatic (OR 1.4, p < 0.001) hypoglycaemia was reported after flash monitoring. Following flash monitoring, regimen-related and emotional components of the diabetes distress scale improved although the proportion with elevated anxiety (OR 1.2, p = 0.028) and depression (OR 2.0, p < 0.001) scores increased. Blood glucose test strip use fell from 3.8 to 0.6 per day (p < 0.001). Diabetic ketoacidosis admissions fell significantly following flash monitoring (p = 0.043).Conclusions/interpretationFlash monitoring is associated with significant improvements in HbA1c and fewer diabetic ketoacidosis admissions. Higher rates of hypoglycaemia may relate to greater recognition of hitherto unrecognised events. Impact upon quality of life parameters was mixed but overall treatment satisfaction was overwhelmingly positive.

Economic Value of Improved Accuracy for Self-Monitoring of Blood Glucose Devices for Type 1 and Type 2 Diabetes in England.

The objective was to model clinical and economic outcomes of self-monitoring blood glucose (SMBG) devices with varying error ranges and strip prices for type 1 and insulin-treated type 2 diabetes patients in England. We programmed a simulation model that included separate risk and complication estimates by type of diabetes and evidence from in silico modeling validated by the Food and Drug Administration. Changes in SMBG error were associated with changes in hemoglobin A1c (HbA1c) and separately, changes in hypoglycemia. Markov cohort simulation estimated clinical and economic outcomes. A SMBG device with 8.4% error and strip price of £0.30 (exceeding accuracy requirements by International Organization for Standardization [ISO] 15197:2013/EN ISO 15197:2015) was compared to a device with 15% error (accuracy meeting ISO 15197:2013/EN ISO 15197:2015) and price of £0.20. Outcomes were lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). With SMBG errors associated with changes in HbA1c only, the ICER was £3064 per QALY in type 1 diabetes and £264 668 per QALY in insulin-treated type 2 diabetes for an SMBG device with 8.4% versus 15% error. With SMBG errors associated with hypoglycemic events only, the device exceeding accuracy requirements was cost-saving and more effective in insulin-treated type 1 and type 2 diabetes. Investment in devices with higher strip prices but improved accuracy (less error) appears to be an efficient strategy for insulin-treated diabetes patients at high risk of severe hypoglycemia.

Initiation of insulin pump therapy in children at diagnosis of type 1 diabetes resulted in improved long-term glycemic control.

Insulin pump therapy (IPT) is increasingly used in children and young people with type 1 diabetes. There are limited studies evaluating the optimal time to start IPT. The aim of this study was to determine if early initiation of IPT in children with type 1 diabetes leads to improved glycaemic control and quality of life (QOL) compared with the later introduction of IPT. There were 38 subjects in the early pump group (EPG) (age 12.6 + 4.9 yr, 23 male) and 37 in the later pump group (LPG) (age 13.1 + 4.1 yr, 19 male). Hemoglobin A1c (HbA1c), rate of severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected retrospectively over a 48-month period. Eligible subjects and/or their parents completed both a Paediatric and Paediatric Diabetes-specific Quality of Life Inventory. HbA1c measurements were lower in the EPG (6.8%; 51 mmol/mol) compared to the LPG (7.9%; 63 mmol/mol), across the 48 months of the study (p < 0.0001). There was no significant difference in the rate (per patient years) of severe hypoglycaemia (0.02; 0.07) p = 0.075 between the two groups. There were no episodes of DKA in either group. There was no significant difference in QOL between the groups with both having high satisfaction rates. Initiation of IPT at diagnosis of type 1 diabetes in children resulted in consistently lower HbA1c with no apparent change in hypoglycemia, DKA, or QOL.

Hypoglycemia-Induced Decrease of EEG Coherence in Patients with Type 1 Diabetes.

Hypoglycemic events in patients with type 1 diabetes (T1D) are associated with measurable electroencephalography (EEG) changes. Previous studies have, however, evaluated these changes on a single EEG channel level, whereas multivariate analysis of several EEG channels has been scarcely investigated. The aim of the present work is to use a coherence approach to quantitatively assess how hypoglycemia affects mutual connectivity of different brain areas. EEG multichannel data were obtained from 19 patients with T1D (58% males; mean age, 55 ± 2.4 years; diabetes duration, 28.5 ± 2.6 years; glycated hemoglobin, 8.0 ± 0.2%) who underwent a hyperinsulinemic-hypoglycemic clamp study. The information partial directed coherence (iPDC) function was computed through multivariate autoregressive models during eu- and hypoglycemia in the theta and alpha bands. In passing from eu- to hypoglycemia, absolute values of the iPDC function tend to decrease in both bands in all combinations of the considered channels. In particular, the scalar indicator [Formula: see text], which summarizes iPDC information, significantly decreased (P < 0.01) in 17 of 19 subjects: from T5-A1A2 to C3-A1A2 from O1-A1A2 to C4-A1A2 and from O2-A1A2 to Cz-A1A2 in the theta band and from O1-A1A2 to T4-A1A2 and from O1-A1A2 to C4-A1A2 in the alpha band. The coherence decrease measured by iPDC in passing from eu- to hypoglycemia is likely related to the progressive loss of cognitive function and altered cerebral activity in hypoglycemia. This result encourages further quantitative investigation of EEG changes in hypoglycemia and of how EEG acquisition and real-time processing can support hypoglycemia alert systems.

Clinical experience of switching from biphasic human insulin to biphasic insulin aspart 30 in Indian patients with type 2 diabetes in the A1chieve study.

Aim:The aim of the following study is to evaluate the safety and effectiveness of switching from biphasic human insulin (BHI) to biphasic insulin aspart 30 (BIAsp 30) in Indian patients with type 2 diabetes as a sub-analysis of the 24-week, non-interventional A1chieve study.Materials and Methods:Indian patients switching from BHI to BIAsp 30 based on the physicians’ decisions were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemic events; secondary outcomes included changes in hypoglycemia in the 4 weeks preceding baseline and week 24 and changes from baseline to week 24 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), body weight and quality of life (QoL).Results:Overall, 1976 patients (mean ± standard deviation age, 55.1 ± 10.6 years and diabetes duration, 10.1 ± 5.3 years) on a mean pre-study BHI dose of 0.44 ± 0.18 U/kg were included. The mean BIAsp 30 dose was 0.43 ± 0.17 U/kg at baseline and 0.44 ± 0.17 U/kg at week 24. No SADRs were reported. The proportion of patients reporting overall hypoglycemic events reduced significantly from baseline to week 24 (15.0% vs. 2.9%, P < 0.0001). The mean HbA1c level improved significantly from 9.1 ± 1.4% at baseline to 7.5 ± 1.0% at week 24, along with improvements in FPG, post-breakfast PPPG and QoL (P < 0.001). The mean body weight decreased from 69.3 ± 10.8 kg at baseline to 69.1 ± 10.4 kg at week 24 (P = 0.003).Conclusion:Switching from BHI to BIAsp 30 therapy was well-tolerated and was associated with improved glycemic control.

Switching from biphasic human insulin to biphasic insulin aspart 30 in type 2 diabetes: Results from the ASEAN subgroup of the A1chieve study

AimTo evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A1chieve study. MethodsIndonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians’ discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire. ResultsFor the 465 patients included (mean±SD age: 56±10.3 years, diabetes duration: 9.7±7.1 years, baseline HbA1c: 9.4±1.8%), the mean pre-study BHI dose was 0.62±0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65±0.27U/kg, titrated up to 0.71±0.28U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p < 0.0001). Significant improvements in glycaemic control were noted (HbA1c: –1.4±1.7%, FPG: –56.7±72.5 mg/dL, post-breakfast PPPG: –84.8±82.8 mg/dL, p < 0.001). Mean QoL improved by +6.6±14.6 points (p < 0.001). ConclusionBIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI.