Reduction In Hypoglycemia Research Articles

Trends in anti-diabetic medication use, severe hyperglycaemia and severe hypoglycaemia among American Indian and Alaska Native Peoples, 2009-2013.

Type 2 diabetes (T2D) and its complications disproportionally affect American Indian and Alaska Native (AI/AN) peoples. Prescribing decisions for anti-diabetic medications are complicated and require balancing medication benefits, costs and side effects. Little is known about trends in anti-diabetic medication use as well as acute diabetes complications among AI/AN adults. Here, we examined patterns and trends in anti-diabetic medication use and rates of hospital admissions or emergency department (ED) visits due to severe hypoglycaemia and hyperglycaemia among AI/AN adults with T2D. We conducted a retrospective analysis of Indian Health Service (IHS) Improving Health Care Delivery Data Project. A total of 39 183 AI/AN adults aged ≥18 years with T2D who used IHS or Tribal health services during any of the fiscal years (FYs) 2009-2013 were included. Utilization rates of each class of anti-diabetic medications and rates of severe hypoglycaemia and severe hyperglycaemia in emergency room and/or inpatient discharge diagnoses were calculated for each year. Longitudinal statistical models were fitted to examine time trends of anti-diabetic medication use and complications. During 2009-2013, use of metformin (56.0%-60.5%), insulin (31.4%-35.9%) and dipeptidyl peptidase-4 inhibitors (1.4%-9.0%) increased, whereas the use of sulfonylureas (40.3%-32.9%) and thiazolidinediones (TZDs, 31.6%-8.8%) decreased significantly. Trends in severe hypoglycaemia (1.6%-0.8%) and severe hyperglycaemia (2.0%-1.6%) declined gradually. There were significant changes in the utilization of different anti-diabetic medication classes during 2009-2013 among AI/AN adults with T2D. Concurrently, there were significant reductions in severe hypoglycaemia and severe hyperglycaemia.

5185 A Meta-Analysis Evaluating the Efficacy of Liraglutide in Reducing Cardiovascular Complications Among Patients With Type 2 Diabetes

Abstract Disclosure: M.P. Del Rosario: None. C. Ong-Ramos: None. Background: The objective of this study was to determine the efficacy of Liraglutide in reducing cardiovascular complications Methodology: Literature searches of electronic databases (PubMed and ScienceDirect) were performed to identify relevant studies. Relevant journals included were electronically searched for randomized controlled trials (RCTs) regarding the use of Liraglutide versus placebo in reducing the rate of cardiovascular complications. Data extraction and quality assessment were done from independent reviewers. Statistical analysis of the study was accomplished using Cochrane Systematic Review Software Review Manager. A p-value of less than 0.05 for the observed effect size was considered statistically significant. Results: A total of 2 RCTs with 16, 977 patients were included in this meta-analysis. The results showed that in the Liraglutide group there is a lower rate of the following: Major Adverse Cardiovascular Events (MACE) (risk ratio of 0.86 [0.78, 0.95]), cardiovascular events (risk ratio 0.75 [0.63, 0.89]), and all-cause mortality (risk ratio 0.81 [0.70, 0.93]), but is not statistically significant when compared to the placebo group in terms of non-fatal myocardial infarction and and non-fatal stroke. There is no significant difference in rates of severe adverse events in general (p > 0.05). However, Liraglutide caused significant reduction in rates of severe hypoglycemia as an independent secondary outcome (p < 0.05). Conclusions: Compared with placebo, Liraglutide provided significant reduction in MACE, cardiovascular events, all-cause mortality and severe hypoglycemia as an adverse event. Presentation: 6/3/2024

HIT4HYPOS Continuous Glucose Monitoring Data Analysis: The Effects of High-Intensity Interval Training on Hypoglycemia in People With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Aims: To assess the impact of high-intensity interval training (HIIT) on hypoglycemia frequency and duration in people with type 1 diabetes (T1D) with impaired awareness of hypoglycemia (IAH). Methods: Post hoc analysis of four weeks of continuous glucose monitoring (CGM) data from HIT4HYPOS; a parallel-group study comparing HIIT + CGM versus no exercise + CGM in 18 participants with T1D and IAH. Results: When compared with those participating individuals not exercising, HIIT did not increase total hypoglycemia frequency, THypo(L1) 1.44 [1.00-2.77]% versus 2.53 [1.46-4.23]%; P = .335, THypo(L2) 0.25 [0.09-0.37]% versus 0.45 [0.20-0.78]%; P = .146, HIIT + CGM versus CGM, respectively, rate ( EventPerWeekHypo 5.30 [3.35-8.27] #/week vs 7.45 [3.54-10.81] #/week, P = .340) or duration ( DurationHypo 33.33 [27.60-39.10] minutes vs 39.56 [31.00-48.38] minutes; P = .219, HIIT + CGM vs CGM, respectively). There was a reduction in nocturnal hypoglycemia in those who carried out HIIT, THypo(L1) 0.50 [0.13-0.97]% versus 2.45 [0.77-4.74]%; P = .076; THypo(L2) 0.00 [0.00-0.03]% versus 0.49 [0.13-0.74]%; P = .006, HIIT + CGM versus CGM, respectively. Conclusions/interpretation: Based on CGM data collected from a real-world study of four weeks of HIIT versus no exercise in individuals with T1D and IAH, we conclude that HIIT does not increase hypoglycemia, and in fact reduces exposure to nocturnal hypoglycemia.

Initiation or switch to insulin degludec/insulin aspart in adults with type 2 diabetes in India: Results from a prospective, non-interventional, real-world study.

To investigate clinical outcomes in adults with type 2 diabetes (T2D) after insulin degludec/insulin aspart (IDegAsp) treatment in a real-world setting. The 26 weeks study involved 1102 adults with T2D who were either initiated with or switched to IDegAsp according to local practice in six countries. It was an open-label, non-interventional study. The primary endpoint was the change in glycosylated haemoglobin (HbA1c) levels from baseline to the end of study (EOS). From India, 185 adults participated in this study with mean age of 58.1 (10.3) years and 14.4 (8.1) years of mean duration of T2D. Mean HbA1c decreased from 9.8% (1.8) at baseline to 8.2% (0.1) at the EOS; change in HbA1c from baseline [95% CI]: -1.6% (0.1) [-1.8; -1.4], P < 0.0001. There was a significant reduction in mean fasting plasma glucose (FPG) level from 190.0 (65.8) mg/dl at baseline to 141.9 (4.3) mg/dl at EOS; change in FPG from baseline [95% CI]: -52.2 (4.3) mg/dl [-60.7; -43.7], P < 0.0001. There was a numerical reduction in resource utilization related to diabetes and its complications and hypoglycaemic episodes. From baseline to EOS, the participants with outpatient visits (72 to 32) and workdays missed (2 to 0) decreased. Additionally, the number of patient-reported non-severe hypoglycaemic (47 to 8) and severe hypoglycaemic (4 to 1) episodes decreased as well. Initiation or switching to IDegAsp led to improvement in glycaemic control in real-world population of Indian adults with T2D. This was accompanied by a numerical reduction in resource utilization and patient-reported hypoglycaemia. Clinical trial registration: NCT04042441.

Continuous glucose monitoring for self-management of diabetes in people living with type 2 diabetes mellitus on basal insulin therapy: A microsimulation model and cost-effectiveness analysis from a US perspective with relevance to Medicaid.

Reducing the risks of complications is a primary goal of diabetes management, with effective glycemic control a key factor. Glucose monitoring using continuous glucose monitoring (CGM) technology is an important part of diabetes self-management, helping patients reach and maintain targeted glucose and glycated hemoglobin (HbA1c) levels. Although clinical guidelines recommended CGM use, coverage by Medicaid is limited, likely because of cost concerns. To assess the cost-effectiveness of FreeStyle Libre CGM systems, compared with capillary-based self-monitoring of blood glucose (SMBG), in US individuals with type 2 diabetes mellitus using basal insulin. A patient-level microsimulation model was used to compare CGM with SMBG for a population of 10,000 patients. A 10-year horizon was used, with an annual discount rate of 3.0% for costs and utilities. Model population characteristics were based on US national epidemiology data. Patient outcomes were based on published clinical trials and real-world studies. Annual costs, reflective of 2023 values, included CGM and SMBG acquisition costs and the costs of treating diabetic ketoacidosis, severe hypoglycemia, and diabetes complications. The effect of CGM was modeled as a persistent 1.1% reduction in HbA1c relative to SMBG based on US real-world evidence. Disutilities were based on published clinical trials and other relevant literature. The primary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to test the validity of the model results when accounting for a plausible variation of inputs. In the base case analysis, CGM was dominant to SMBG, providing more QALYs (6.18 vs 5.97) at a lower cost ($70,137 vs $71,809) over the 10-year time horizon. A $10,456 increase in glucose monitoring costs was offset by a $12,127 reduction in treatment costs. Cost savings reflected avoidance of acute diabetic events (savings owing to reductions in severe hypoglycemia and diabetic ketoacidosis were $271 and $2,159, respectively) and a reduced cumulative incidence of diabetes complications, particularly renal failure (saving $5,292), myocardial infarction (saving $1,996), and congestive heart failure (saving $1,061). Scenario analyses were consistent with the base case results, and the incremental cost-effectiveness ratio for CGM vs SMBG ranged from dominant to cost-effective. In probabilistic analysis, CGM was 100% likely to be cost-effective at a willingness-to-pay threshold of $50,000/QALY. CGM is cost-effective compared with SMBG for US patients with type 2 diabetes mellitus receiving basal insulin therapy. This suggests that state Medicaid programs could benefit from broader coverage of CGM.

A single-site feasibility randomised controlled trial comparing 'my hypo compass' short pyscho-educational intervention with standard care alone in individuals with type 1 diabetes and impaired awareness of hypoglycaemia.

The HypoCOMPaSS multi-centre trial achieved improvement in hypoglycaemia awareness and 20-fold reduction in severe hypoglycaemia (SH) in a cohort with long-standing type 1 diabetes (T1D). All participants received 'my hypo compass' (MHC) brief structured psycho-educational intervention in addition to optimisation of insulin delivery/glucose monitoring. In this 24-week, prospective, single-centre feasibility RCT, we piloted MHC as a sole intervention in comparison to standard clinical care alone (CON). Participants with T1D and impaired hypoglycaemia awareness (IAH) (Clarke score ≥4) were recruited. MHC comprised a group/individual 1-2 h face-to-face session followed by a telephone call and second face-to-face session at 4 weeks. Outcome measures at 24 weeks were compared with baseline. Fifty-two individuals provided consent for screening with 39 fulfilling eligibility criteria. Fifteen withdrew before any study intervention. Twenty-four adults with (mean ± SD) T1D duration 41.0 ± 15.1 years commenced/completed the study (100% visit attendance); 12 randomised to MHC and 12 to CON. All had IAH at baseline and at 24 weeks. Annualised SH rate following MHC was 3.8 ± 19.0 (24 weeks) versus 12.6 ± 3.5 (Baseline) and in CON group 2.0 ± 19.0 (24 weeks) versus 4.6 ± 11.5 (Baseline). 'Immediate Action' for and 'Worry' about hyperglycaemia measured by the Hyperglycaemia Avoidance Scale appeared lower following MHC. Participants attended all study visits and reflected positively on the MHC intervention. Feasibility of MHC implementation without additional intervention has been demonstrated. MHC education was associated with positive changes in attitudes and behaviours with the potential to reduce SH risk. MHC provides a validated, simple, well-received programme to fulfil the educational component within RCTs targeting problematic hypoglycaemia and as part of holistic clinical care.

Population-Based Study on the Implementation of Flash Glucose Monitoring and Severe Hypoglycemia in Adults With Type 1 Diabetes.

Objective: We analyzed the effect of implementing a flash glucose monitoring (FGM) technology in a public health care system with universal coverage on the rate of severe hypoglycemia requiring urgent care in adults with type 1 diabetes mellitus (T1DM). Methods: Using a comprehensive regional dataset, we extracted emergency care codes with hypoglycemia in individuals with T1DM who initiated the use of FGM in Andalucia, Spain, from January 1, 2020, to December 31, 2021. Severe hypoglycemia was defined as a confirmed blood glucose <70 mg/dL, which required the urgent dispatch of an emergency medical service (EMS) for onsite management. We compared hypoglycemic events reported in the 12 months before and after the initiation of FGM to determine the population incidence rates. Results: A total of 13,616 participants with a mean age of 43.7 ± 13.5 years were included. The follow-up periods were 23.4 and 24.8 months before and after FGM. There were 969 and 737 cases of hypoglycemia before and after the initiation of FGM. The baseline incidence rate was 358.58 episodes per 10,000 person-years, which decreased to 260.9 at the end of the follow-up (rate-ratio 0.72 [0.66; 0.80]). The reduction in hypoglycemia was significant in individuals aged ≥60 years (rate-ratio 0.40 [0.28; 0.55]) and males (0.64 [0.56; 0.72]). In addition, there was a reduction in the overall median HbA1c of -0.35% (95% CI [-0.38; -0.33], P < 0.001). Conclusion: The implementation of FGM systems in a public health care system as a provision for adults with T1DM was associated with significant reductions in the rate of severe hypoglycemic events that required urgent EMS care.

239-OR: CGM Has a Specific Effect on the Reduction of Nocturnal Hypoglycemia in People with Type 1 Diabetes on an MDI Treatment Regimen

MDI users with type 1 diabetes may be less able to respond to circadian changes in insulin demand than CSII or AID users, which may increase the risk of nocturnal hypoglycemia. Therefore, we re-analyzed data from the HYPO.DE RCT to evaluate the effect of CGM on the percentage of low glucose levels &amp;lt; 70 mg/dl (% &amp;lt; 70 mg/dl) and &amp;lt; 54 mg/dl (% &amp;lt; 54 mg/dl) during 12 two-hour periods throughout the day. We compared 4-week baseline data from 141 participants using spot glucose monitoring (SMBG) with 4-week outcome data after a 6-month follow-up period in which the control group (n=66) remained on SMBG and the intervention group (n=75) used CGM (Dexcom G5). At baseline without CGM, there were significantly higher proportions of %&amp;lt;70 mg/dl or %54 mg/dl during the night (00:00 am - 06:00 am) than during the day (8.5 ±1.0% vs. 6.5 ±0.6%, p&amp;lt;0.001 respectively 4.0 ±0.6% vs. 2.4 ±0.3%, p&amp;lt;0.001). CGM had a greater effect on nocturnal hypoglycemia than on daytime hypoglycemia (see Figure 1). The greatest reduction in favor of the CGM users was between 04:00 a.m. and 06:00 a.m., with a between-group difference of -8.5% (95% CI -10.4% to -6.7%, p&amp;lt;.001) for %&amp;lt;70 mg/dl and -5.5% (95% CI 4.4 - 6.6%, p&amp;lt;.001) for %&amp;lt;54 mg/dl. The data suggest that CGM provides benefits to MDI users with type 1 diabetes in preventing nocturnal hypoglycemia, potentially compensating for lack of responsiveness to a circadian changing insulin demand. Disclosure N. Hermanns: Speaker's Bureau; Berlin-Chemie AG, Sanofi-Aventis Deutschland GmbH. Research Support; Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Roche Diabetes Care. Research Support; Roche Diabetes Care. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Abbott Diagnostics, Ypsomed AG. D. Ehrmann: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Sanofi-Aventis Deutschland GmbH. Advisory Panel; Roche Diabetes Care. Speaker's Bureau; Roche Diabetes Care, Berlin-Chemie AG. B. Kulzer: Advisory Panel; Abbott Diagnostics, Berlin-Chemie AG, Dexcom, Inc., Sanofi, embecta, Novo Nordisk, Roche Diabetes Care. Speaker's Bureau; Bayer Inc., Insulet Corporation, Lilly Diabetes. G. Freckmann: Advisory Panel; Abbott. Research Support; Ascensia Diabetes Care. Advisory Panel; Boydsense, Dexcom, Inc., Lilly Diabetes. Speaker's Bureau; Novo Nordisk. Advisory Panel; Perfood, PharmaSens. Consultant; Roche Diabetes Care. Research Support; Roche Diabetes Care. Consultant; Sinocare. Speaker's Bureau; Terumo Corporation. Consultant; Ypsomed AG. L. Heinemann: Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH. Advisory Panel; embecta. Board Member; Lifecare A/S. Stock/Shareholder; diateam GmbH. Funding The HYPO.DE study was funded by Dexcom, San Diego

Management of non-malignant hyperinsulinemic hypoglycaemia in resource limited setting: a case report

A 37 y.o. Asian male presented with frequent hypoglycaemia in both fasting and post-prandial state. He had elevated blood insulin levels during the hypoglycaemic episodes with normal pancreatic morphology and no extra-pancreatic tumor. Through systematic symptom assessment and the use of simple laboratory examination, non-insulinoma pancreatogenous hypoglycaemia syndrome presented as the most likely diagnosis. Conclusive aetiological diagnosis could not be reached due to the limited availability of diagnostic modalities. Nevertheless, modest symptom control and frequency reduction of hypoglycaemia were achieved with empirical dietary modification and α-glucosidase inhibitor treatment.

A register-based study describing time trends in risk factor control and serious hypoglycaemia together with the effects of starting continuous glucose monitoring in people with type 1 diabetes in Norway.

To describe trends in risk factor control and serious hypoglycaemia in people with type 1 diabetes and to assess the effect of starting continuous glucose monitoring (CGM) in the real-world setting. Two cross-sectional surveys including 5746 individuals in 2012 and 18,984 individuals in 2020 based on data recorded in the Norwegian Diabetes Register for Adults (NDR-A) and an analysis of a longitudinal cohort of 2057 individuals where data on CGM and HbA1c were available in the NDR-A in 2012 and 2020. In the cross-sectional surveys mean HbA1c decreased from 66 mmol/mol (99% CI 65, 66) (8.2%) in 2012 to 61 mmol/mol (99% CI 61, 61) (7.7%) in 2020 (p < 0.0001). The proportion reporting serious hypoglycaemia decreased from 16.9 to 6.2% in 2020 (p < 0.0001). Mean LDL-cholesterol decreased from 2.80 (99% CI 2.78, 2.83) to 2.63 (99% CI 2.61, 2.65) mmol/l in 2020 (p < 0.0001). Mean blood pressure increased slightly. In the CGM cohort, we found a 3 mmol/mol (0.3%) greater improvement in mean HbA1c and a greater reduction in serious hypoglycaemia (-12.3% vs. -6.2%) among individuals that had started using CGM between 2013 and 2020 when compared with individuals that had not started using CGM. Between 2012 and 2020, we found marked improvements in glycaemic control and a considerable decrease in the proportion of individuals reporting serious hypoglycaemia. The proportion of individuals using CGM increased substantially and individuals that had started using CGM by 2020 showed greater improvement in glycaemic control and less serious hypoglycaemia.

Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

Can Unmet Needs Be Addressed by Adjunctive Therapies? Findings from a Patient Perspectives Survey in Adults with Type 1 Diabetes.

Many individuals with type 1 diabetes (T1D) do not achieve their management goals. The patient perspective on unmet needs in T1D may guide the role of adjunctive therapies, including glucagon like peptide-1 receptor agonists (GLP-1RAs). A quantitative online survey (n = 133) assessed (1) self-reported demographic and management data, (2) management priorities, satisfaction, and willingness to use adjunctive therapies and (3) conducted a risk-benefit analysis using three masked drug profiles (1.8 mg vs 0.6 mg liraglutide vs placebo). A subgroup of respondents (n = 20) participated in semi-structured interviews to extend upon survey insights. Needs were unmet by current treatment in 28% of surveyed individuals. The greatest unmet needs included (1) glycemia, (2) management-related fatigue, and (3) weight management. Most respondents (94%) indicated that they would use adjunctive therapies. The preferred administration route was daily tablets (66%) followed by weekly injections (32%). Metabolic improvements were most valued (reduction in hypoglycemia, hyperglycemia). Most respondents (94%) preferred the liraglutide risk-benefit profile (1.8 mg, then 0.6 mg) over placebo. Individuals with T1D self-report many unmet needs. While not currently approved in T1D, GLP-1RA properties align with many management priorities reported by individuals with T1D.

Improvement of blood glucose control and reduction of hypoglycemia, body weight, and C-reactive protein in type 1 diabetic patients treated with intensive insulin therapy with insulin analogs

Background/Aim. Good metabolic control can delay the onset and progression of chronic complications of diabetes mellitus (DM). Intensified insulin therapy (IIT) is the cornerstone of good metabolic control in the treatment of type 1 DM (T1DM) while avoiding hypoglycemia and body weight (BW) gain in those patients. The aim of the study was to assess the effects of IIT with insulin analogs (aspart and glargine) in T1DM patients. Methods. This prospective clinical study included 49 patients with at least one year of T1DM duration, who were on IIT with human insulin at that moment. They commenced therapy with insulin aspart for three months, followed by insulin glargine for another three months. An analysis of blood glucose (BG) control (glycated hemoglobin ? HbA1c, mean BG, fasting BG, postprandial BG, and glycemic variability) and analysis of BW, hypoglycemia, and C-reactive protein (CRP) levels were performed. Results. The HbA1c level decreased slightly (non-significantly) after three months of insulin aspart therapy (from 9.28% to 8.83%) and decreased significantly after the aspart/glargine combination (to 8.08%; p &lt; 0.001). After the first three months with aspart therapy, a significant reduction in postprandial BG was noted after all three main meals. The mean postprandial rise of BG was significantly reduced. The variability of daily BG was significantly reduced (standard deviation of BG fell from 2.28 mmol/L to 1.90 mmol/L; p &lt; 0.05). The mean BG value in the profiles decreased (from 9.11 mmol/L to 8.31 mmol/L; p &lt; 0.05). All BG values in the profiles after six months were statistically significantly lower compared to the initial values, as well as the mean BG (6.88 mmol/L; p &lt; 0.001) and the variability of daily BG (1.49 mmol/L; p &lt; 0.01). Our results showed a significant reduction in the number of hypoglycemias after three months, especially after the introduction of insulin glargine therapy (significant reduction in the number of symptomatic, asymptomatic, and nocturnal hypoglycemias). The results showed a discrete but significant reduction in BW and a significant reduction in CRP levels (from 3.43 mg/L to 2.25 mg/L; p &lt; 0.001). Conclusion. Treatment of patients with T1DM with insulin analogs (insulin aspart and insulin glargine) in IIT leads to improved BG control with a reduction in the number of hypoglycemia, BW, and CRP levels.

Impact of a Hyperkalemia Protocol Tailored to Glucose Concentration and Renal Function on Insulin-Induced Hypoglycemia in Patients with Low Pretreatment Glucose

BackgroundHyperkalemia is a common electrolyte abnormality that requires urgent treatment. Insulin is an effective treatment for hyperkalemia, but risk factors for developing insulin-induced hypoglycemia exist (e.g., low pretreatment glucose or renal impairment). ObjectiveThis study evaluated the impact of a hyperkalemia protocol tailored to glucose concentration and renal function on insulin-induced hypoglycemia. MethodsThis was a retrospective cohort study of emergency department patients with glucose ≤ 100 mg/dL treated with insulin for hyperkalemia. The primary outcome was incidence of hypoglycemia in patients treated prior to (July 1, 2018–June 30, 2019) vs. after (January 1, 2020–December 31, 2020) the protocol update, which individualized insulin and dextrose doses by glucose concentration and renal function. Secondary outcomes included change in potassium and protocol safety. We assessed factors associated with hypoglycemia using multiple logistic regression. ResultsWe included 202 total patients (preimplementation: 114, postimplementation: 88). Initial insulin dose was lower in the postimplementation group (p < 0.001). We found a nonsignificant reduction in hypoglycemia in the postimplementation group (42.1% vs. 30.7%, p = 0.10). Degree of potassium reduction was similar in patients who received insulin 5 units vs. 10 units (p = 0.72). Higher pretreatment glucose (log odds ratio [OR] −0.05, 95% confidence interval [CI] −0.08 to −0.02) and additional insulin administration (log OR −1.55, 95% CI −3.01 to −0.25) were associated with reduced risk of developing hypoglycemia. ConclusionA hyperkalemia protocol update was not associated with a significant reduction in hypoglycemia, and the incidence of hypoglycemia remained higher than anticipated. Future studies attempting to optimize treatment in this high-risk population are warranted.

Effectiveness, safety and costs of the FreeStyle Libre glucose monitoring system for children and adolescents with type 1 diabetes in Spain: a prospective, uncontrolled, pre-post study

ObjectivesThis study aimed to evaluate the effectiveness, safety and costs of FreeStyle Libre (FSL) glucose monitoring system for children and adolescents with type 1 diabetes mellitus (T1DM) in Spain.DesignProspective, multicentre...

The effect of insulin analogs in people with type 1 diabetes at increased risk of severe hypoglycemia

Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery, insulin therapy has evolved, and since the 1990s, an increasing number of insulin analogs with various pharmacokinetic and pharmacodynamic profiles have become available. Despite the improvement of insulin therapy, hypoglycemia remains the main side effect and is a daily concern for many people with diabetes and their families. A proportion of people with type 1 diabetes are at increased risk of hypoglycemia and experience recurring episodes. When designing insulin trials, this group of people is most often excluded in order to reduce the risk of adverse study outcomes, even though it may be the group that may benefit the most from treatment with new insulins. The results of the phase III trials, therefore, underestimate the clinical impact and pharmacoeconomic effect of the implementation of new insulins in the broader type 1 diabetes population. This paper reviews the four insulin trials that include people at increased risk of hypoglycemia. In general, the studies confirm the results from phase III trials in terms of similar reduction and maintenance of HbA1c, as well as relative rate reductions of hypoglycemia. However, the absolute treatment differences in the reduction of hypoglycemia are even greater in the trials, including people at high risk of hypoglycemia. This emphasizes the importance of including people at high risk of hypoglycemia to assess the full clinical and pharmacoeconomic benefit of new insulins.

C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis

Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes. 21 trials of disease-modifying interventions within 100 days of type 1 diabetes diagnosis comprising 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years) were combined. Endpoints assessed were stimulated area under the curve C-peptide, HbA1c, insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A1c, total daily insulin, U/kg per day, and BETA-2 score). Positive studies were defined as those meeting their primary endpoint. Differences in outcomes between active and control groups were assessed using the Wilcoxon rank test. 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA1c (p<0·0001), with differences being detectable as early as 3 months. Cross-sectional analysis, combining positive and negative studies, was consistent with this proportionality: a 55% improvement in C-peptide preservation was associated with 0·64% lower HbA1c (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA1c. For HbA1c, IDAAC, and BETA-2 score, sample size predictions indicated that 2-3 times as many participants per group would be required to show a difference at 6 months as compared with C-peptide. Detecting a reduction in hypoglycaemia was affected by reporting methods. Interventions that preserve β-cell function are effective at improving metabolic outcomes in new-onset type 1 diabetes, confirming their potential as adjuncts to insulin. We have shown that improvements in HbA1c are directly proportional to the degree of C-peptide preservation, quantifying this relationship, and supporting the use of C-peptides as a surrogate endpoint in clinical trials. JDRF and Diabetes UK.

Increasing Exclusive Nursery Care of Late Preterm and Low Birth Weight Infants.

Late preterm (LPT) and low birth weight (LBW) infants are populations at increased risk for NICU admission, partly due to feeding-related conditions. This study was aimed to increase the percentage of LPT and LBW infants receiving exclusive nursery care using quality improvement methodologies. A multidisciplinary team implemented interventions at a single academic center. Included infants were 35 to 36 weeks gestational age and term infants with birth weights <2500 g admitted from the delivery room to the nursery. Drivers of change included feeding protocol, knowledge, and care standardization. We used statistical process control charts to track data over time. The primary outcome was the percentage of infants receiving exclusive nursery care. Secondary outcomes included rates of hypoglycemia, phototherapy, and average weight loss. Balancing measures were exclusive breast milk feeding rates and length of stay. Included infants totaled 1336. The percentage of LPT and LBW infants receiving exclusive nursery care increased from 83.9% to 88.8% with special cause variation starting 1 month into the postintervention period. Reduction in neonatal hypoglycemia, 51.7% to 45.1%, coincided. Among infants receiving exclusive nursery care, phototherapy, weight loss, exclusive breast milk feeding, and length of stay had no special cause variation. Interventions involving a nursery feeding protocol, knowledge, and standardization of care for LPT and LBW infants were associated with increased exclusive nursery care (4.9%) and reduced rates of neonatal hypoglycemia (6.6%) without adverse effects. This quality initiative allowed for the preservation of the mother-infant dyad using high-value care.

Validation of Igls Criteria for Islet Transplant Functional Status Using Person-Reported Outcome Measures in a Cross-Sectional Study.

Associations between islet graft function and well-being in islet transplant recipients requiring exogenous insulin remain unclear. This cross-sectional analysis compared person-reported outcome measures in 15 adults with type 1 diabetes whose islet transplants were classified according to Igls criteria as "Good" (n = 5), "Marginal" (n = 4) and "Failed" (n = 6) graft function. At a mean of 6.2years post-first islet transplant, 90% reduction in severe hypoglycaemia was maintained in all groups, with HbA1c (mean ± SD mmol/mol) 49 ± 4 in recipients with "Good" function; 56 ± 5 ("Marginal"); and 69 ± 25 ("Failed"). Self-reported impaired awareness of hypoglycaemia persisted in all groups but those with "Good" function were more likely to experience symptoms during hypoglycaemia. "Marginal" function was associated with greater fear of hypoglycaemia (HFS-II score: "Marginal": 113 [95, 119]; "Failed": 63 [42, 93] (p = 0.082); "Good": 33 [29, 61]) and severe anxiety (GAD7: "Marginal"): 21 [17, 21]; "Failed": 6 [6, 6] "Good": 6 [3, 11]; (p = 0.079)), diabetes distress and low mood. Despite clear evidence of ongoing clinical benefit, Igls criteria 'Marginal' function is associated with sub-optimal well-being, including greater fear of hypoglycaemia and severe anxiety. This study provides person-reported validation that "Good" and "Marginal" graft function are differentiated by general and diabetes-specific subjective well-being, suggesting those with "Marginal" function may benefit from further intervention, including re-transplantation.

149-LB: Telemedicine Intervention Impact on Diabetes Self-Management—Twelve-Month Virtual Diabetes Specialty Clinic (VDISC) Study Outcomes

The impact of a telemedicine model for a virtual diabetes clinic was assessed 6 months following completion of a 6-month intervention of education and support for diabetes self-management, including initiation and use of CGM. One hundred and sixty-one participants ≥18 years old with T1D (N=109) or T2D (N=52) using MDI/pump participated in the 12-month study. At the end of the 6-month intervention period, mean HbA1c decreased from 7.6% at baseline to 7.0% in T1D and from 8.1% to 7.0% in T2D (P&amp;lt;0.001). At 12 months (6 months after discontinuation of the intervention), mean HbA1c was 7.0% for T1D and 7.2% for T2D (P&amp;lt;0.001 compared with baseline). Mean time in range 70-180 mg/dL was 51% at baseline, increasing to 62% at 6 months (P&amp;lt;0.001) and 64% at 12 months in T1D (P&amp;lt;0.001) and from 49% to 66% (P&amp;lt;0.001) and 68% (P&amp;lt;0.001), respectively, in T2D. Similar improvements were observed for mean glucose and hyperglycemia metrics. A sustained reduction in hypoglycemia also was observed. The virtual diabetes clinic intervention was successful in promoting improved glycemic outcomes, which were sustained 6 months after the intervention was completed. These findings demonstrate the impact that virtual care and education can have on self-management over time and provide opportunity to expand care models that could minimize barriers to specialty care access. Disclosure R. L. Gal: None. S. Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T. Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. K. K. Hood: Consultant; Cecelia Health. T. L. Cushman: None. M. L. Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. 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. D. Raghinaru: None. G. Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. B. A. Olson: Stock/Shareholder; Abbott. D. F. Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. R. M. Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. R. S. Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. A. Bradshaw: None. T. S. Mcarthur: None.