Moderate Hypoglycemic Events Research Articles

891-P: Hypoglycemia Prevention Behaviors Prevent Moderate Hypoglycemic Events: The REPLACE-BG Trial

Background: Continuous glucose monitoring (CGM) provides real-time glucose levels and alarms for hypoglycemia. We analyze CGM data from the REPLACE-BG trial, which had 6 months of CGM data on people with well controlled type 1 diabetes (T1D), to characterize hypoglycemic events and evaluate their association with hypoglycemia-related behaviors. Methods: We conducted a psychometric analysis of the Hypoglycemia Fear Survey- Behavior scale to identify unique hypoglycemia behavior constructs. We identified and categorized hypoglycemic events in CGM data as mild (min glucose <70 mg/dL) and moderate (min glucose <50 mg/dL) and used ANOVA to evaluate differences in the frequency and duration of events by high and low score categories of hypoglycemia behavior constructs. We used multivariate linear regression to evaluate the association between hypoglycemia behavior constructs and 1) duration of moderate hypoglycemic events and 2) proportion of moderate hypoglycemic events. Results: We separated the HFS-B into three scales: hypoglycemia avoidance, reaction, and prevention. In low vs. high hypoglycemia prevention score categories, the duration of moderate hypoglycemic events was significantly longer (73 vs. 66 minutes, p<0.05) and proportion of moderate hypoglycemic events was higher (22.4 vs. 20.1, p<0.1). In multivariate models that included all three hypoglycemia behavior scales, hypoglycemia prevention behavior was significantly, inversely associated with 1) duration of moderate hypoglycemic events (β= -6.9, SE= 2.2, p< 0.01) and 2) proportion of moderate hypoglycemic events (β= -2.2, SE= 0.7, p-value < 0.01). Conclusion: Hypoglycemia is common in T1Ds. The increased likelihood of engaging in hypoglycemia prevention behaviors reduces the frequency and duration of dangerous moderate hypoglycemic events. Analyzing CGM data in its continuous form reveals the frequency and characteristics of individual hypoglycemic events. Disclosure M.A. Crawford: Employee; Self; Dexcom, Inc. M.M. White: None. D.R. Strong: None. J.P. Pierce: None.

A phase 3 multicenter, open-label, prospective study designed to evaluate the effectiveness and ease of use of nasal glucagon in the treatment of moderate and severe hypoglycemia in children and adolescents with type 1 diabetes in the home or school setti

This multicenter, open-label study was designed to evaluate real-world effectiveness and ease of use of nasal glucagon (NG) in treating moderate or severe hypoglycemic events in children and adolescents with type 1 diabetes (T1D). Caregivers were trained to administer NG (3 mg) to the child/adolescent with T1D during spontaneous, symptomatic moderate or severe hypoglycemic events, observe treatment response (defined as awakening or returning to normal status within 30 minutes), and measure blood glucose (BG) levels every 15 minutes. Data regarding adverse events and ease of use were solicited using questionnaires. The analysis population included 14 patients who experienced 33 moderate hypoglycemic events with neuroglycopenic symptoms and BG level ≤70 mg/dL. Patients returned to normal status within 30 minutes of NG administration in all 33 events. Mean BG levels increased from 55.5 mg/dL (range 42-70 mg/dL) at baseline to 113.7 mg/dL (range 79-173 mg/dL) within 15 minutes of NG administration. In most hypoglycemic events (93.9%), caregivers reported that NG administration was easy or very easy; they could administer NG within 30 seconds in 60.6% of events. There were no serious adverse events. A single 3-mg dose of NG was effective in treating moderate, symptomatic, hypoglycemic events in children and adolescents with T1D in a real-world setting. It was easy-to-use and reasonably well tolerated. NG shows promise as an effective, needle-free, and user-friendly alternative to injectable glucagon.

The Real-World Impact Of Mild To Moderate Hypoglycemic Events In Portugal – Results From The Hipos-Pharma Study

We measured the impact of mild to moderate hypoglycemic events occurring in ambulatory Type 2 Diabetes Mellitus (T2DM) patients, including healthcare consumption, productivity losses and disease management. HIPOS-PHARMA was a nationwide observational, cross-sectional, multicenter study performed from 4 April until 20 May 2016 in community pharmacies of Portugal, which surveyed T2DM patients under treatment for at least 3 months. A structured questionnaire was managed by pharmacists, including questions about awareness, prevalence and the impact of hypoglycemic episodes. Among those T2DM patients experiencing a mild to moderate hypoglycemic episode in the previous 3 months (17.8% out of 1890 surveyed T2DM patients) 9.1% required non-scheduled medical/nursing consultations and 9.4% reported absenteeism from work (mean loss of 1.5 working days) as a consequence of such events. In addition, almost a fifth (18.3%) not only required therapeutic modification, mainly dosage modification (68.9%), but also drug switch (18.0%) and temporary treatment interruption (8.2%). The recorded hypoglycemic events also led to a modification of self-monitoring of blood glucose levels in over a third of patients (38.3%; with a mean additional consumption of 2.7 blood glucose test strips). Furthermore, in our study, T2DM patients didn`t fully acknowledge when they were having a hypoglycemic episode (Always: 53.0%; Almost always: 27.1%; Sometimes: 11.1%; Rarely: 5.0%; Never: 3.8%) and that underreporting of these relevant events occurred with only 46.4% of patients reporting it to an healthcare professional (Physician: 80.7%; Pharmacist: 18.7%; Nurse: 17.4%; Other 1.9%). In this nationwide study we observed that mild to moderate hypoglycemic episodes are associated with healthcare consumption, productivity losses and changes in management of Diabetes. Furthermore, we also confirmed that there is a need for improvement in the communication between patients and healthcare professionals in order to increase patient awareness and reporting of diabetes-related hypoglycemic events.

Treatment of Hypoglycemia in Adult Patients with Type 1 Diabetes: An Observational Study

1) To characterize the nutritional treatment of hypoglycemia in adult patients with type 1 diabetes mellitus and 2) to compare the characteristics of participants who follow the recommendations with the characteristics of those who do not. A total of 121 adults with type 1 diabetes were included in this cross-sectional analysis. Participants completed a food record and a glycemia and insulin doses logbook to collect data on mild to moderate hypoglycemic events (glycemia <4.0 mmol/L or 4.0 to 5.0 mmol/L with symptoms) and their treatments over a 2-day period. Participants were identified as overcorrecting if they consumed, within 15 minutes after the episode, >20g of carbohydrates for correction. Self-administered questionnaires about fear of hypoglycemia were completed, and cardiometabolic profile variables were measured (glycated hemoglobin, blood pressure, lipid profile and body mass indexes). Of the 121 participants, 94 (78%) reported at least 1 hypoglycemic event, for a total of 271 events (2.2±2.1 episodes per patient). Of these events, 64% were treated within 15 minutes, and they were treated primarily with fruit juice or sweet beverages (39%) or mixed snacks (29%). Average carbohydrate intake for treatment was 32±24 grams. Of the participants, 73% overtreated their episodes. They were significantly younger and had greater fear of hypoglycemia than those who treated the episodes adequately. No difference was observed for cardiometabolic variables. The majority of patients in our cohort overtreated their hypoglycemic episodes. These results suggest that hypoglycemia-correction education needs to be reinforced.

Utilities for treatment-related adverse events in type 2 diabetes

Objectives:The impact of Type 2 diabetes mellitus (T2DM) on health-related quality-of-life (HRQoL) is complex due to the burden of disease, lifelong treatment requirements, and comorbidities. This study aimed to capture UK societal utility values for health states associated with T2DM and treatment-related adverse events (AEs) to assess the burden of the disease and common AEs.Methods:Nine health state descriptions were developed (from a literature review and patient and clinician qualitative input) depicting the burden associated with T2DM and treatment-related AEs. These were mild/moderate urinary tract infection (UTI); severe UTI; mycotic infection; moderate hypoglycemic events; severe hypoglycemic events; fear of hypoglycemia; gastrointestinal symptoms; and hypovolemic events. Members of the UK general public (n = 100) valued these states using the time trade-off (TTO) methodology to elicit utility values (between 0 = dead, 1 = full health). Regression analysis was conducted to understand the influence of age and gender.Results:All treatment-related AEs were found to have a significant effect on utility. From the T2DM baseline state (0.92), the experience of AEs was associated with the following disutility: T2DM with hypovolemic events (0.08); T2DM with mild/moderate UTIs (0.09); T2DM with moderate hypoglycemic events (0.11); T2DM with severe hypoglycemic events (0.15); T2DM with fear of hypoglycemia (0.15); T2DM with severe UTIs (0.19); T2DM with GI symptoms (0.24); and T2DM with mycotic infection (0.25); Males consistently scored the states with significantly lower utility values, but no significant age effects emerged.Conclusions:Findings suggest that adverse events in T2DM can be a burden for some individuals. The study indicates the potential importance of including information regarding AEs in economic evaluations. Although some states were rated severely in terms of utility; in reality, many of these only last a few days, therefore having a minimal quality-adjusted life year (QALY) impact.

Effect of Sensor-Augmented Insulin Pump Therapy and Automated Insulin Suspension vs Standard Insulin Pump Therapy on Hypoglycemia in Patients With Type 1 Diabetes

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. Patients were randomized to insulin pump only or automated insulin suspension for 6 months. The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. anzctr.org.au Identifier: ACTRN12610000024044.

Comparative efficacy assessment for various insulin regimens in patients with type 2 diabetes mellitus, ischaemic heart disease and frequent hypoglycemic events

Aims. To study influence of combined treatment with human insulin analogues (insulin aspart and insulin detemir) on glycemic control,insulin resistance and development of ischaemic heart disease (IHD) in patients with type 2 diabetes mellitus (T2DM) and frequenthypoglycemic events in comparison with that of human insulins (soluble and isophane). Materials and methods. 54 patients (mean age 61.2?0.7) with T2DM and IHD participated in this study. All included patients experiencedfrequent mild and moderate hypoglycemic events (3+ episodes per week). We analyzed frequency and severity of hypoglycemia,parameters of glycemic and lipid metabolism, number of ischaemic episodes per day, duration and depth of ST depression, circadianindex, incidence of different types of arrhythmia and conduction abnormalities as measured by Holter ECG monitoring.All patients were subdivided into two groups by random sampling: 21 patient (first group) carried on with human soluble insulin andisophane in an optimized basal-bolus regimen. In 33 patients, comprising second group, treatment was changed for combination ofinsulin aspart (NovoRapid?, Novo Nordisk, Denmark) and insulin detemir (Levemir?, Novo Nordisk, Denmark). Follow-up periodwas set to 6 months. Results. In patients with frequent hypoglycemic experience different types of arrhythmia and heart conduction abnormalities wereobserved in 75.9% of cases. Most patients had complex types of arrhythmic disorders (70.4%) with ventricular extrasystole being themost common one. Signs of myocardial ischaemia were registered in 48.1% of patients.After 6 months of follow-up patients from the second group demonstrated a statistically significant decrease in fasting and postprandiallevels of glycemia (p=0.000001). Both groups also had a significantly lower rate of hypoglycemic events. Moreover, in the second groupall episodes of hypoglycemia were mild and occurred only in 36.4% of cases. Additionally, after 6 months of treatment with humaninsulin analogues ventricular extrasystoles were registered only in 24.2% of patients, while rate and duration of ischaemic episodesdropped to 4.25?1.51 (p=0.012, comparing with first group). Conclusion. Treatment with human insulin analogues NovoRapid? and Levemir? is associated with 1.6% decrease in HbA1c levels.Mild hypoglycemia was 72.2% less frequent, as compared with rates in the group on human soluble and isophane insulin, while moderateand severe hypoglycemic events were not observed at all. In turn, decrease in frequency and severity of hypoglycemia was associatedwith substantial improvement in cardiovascular status due to lower number and duration of ischaemic episodes (including painlessvariant) and lower frequency of heart rhythm disorders.

Glycemic Control with Preprandial Versus Basal Insulin in Patients with Type 2 Diabetes Mellitus Poorly Controlled by Oral Antidiabetes Agents

This study was designed to compare glycemic control (glycated hemoglobin [A1C] level) with either once-daily basal insulin (BI) (insulin glargine) or preprandial insulin (PPI) (Exubera) [insulin human (recombinant DNA origin)] inhalation powder, Pfizer Inc., New York, NY) in patients with type 2 diabetes mellitus (T2DM) poorly controlled on at least two oral antidiabetes agents (OADs). This was a 26-week, open-label, parallel-group, randomized study where 257 patients (mean A1C 8.6%) on OAD treatment for > or = 3 months were treated with either BI (n = 122) or PPI (n = 135). Based on self-monitored blood glucose levels, PPI dose was adjusted before each major meal, whereas BI dose was titrated in the morning or before bedtime. Prestudy OADs were continued, but doses could be modified. At 26 weeks, change from baseline in A1C was greater with PPI (-1.7 vs. -1.4%, P = 0.0389). Numerically, more patients achieved A1C <6.5% (28% vs. 19%) and A1C <7.0% (63% vs. 55%) with PPI compared with BI. PPI had lower postmeal glucose increments, but higher prebreakfast glucose and weight gain (1.1kg), than BI. Mild or moderate hypoglycemic events were more frequent with PPI (6.2 vs. 2.9 events/months), but nocturnal hypoglycemic events were less frequent (22% vs. 30%). PPI improved postprandial glucose and A1C levels significantly more than BI. More patients achieved A1C targets with PPI, at the expense of more hypoglycemia and body weight gain. These results illustrate the potential benefits and detriments of prandial insulin supplementation in patients with T2DM poorly controlled on OADs alone.

Cardiovascular Events and Correlates in the Veterans Affairs Diabetes Feasibility Trial

The risks and benefits of intensive therapy in non-insulin-dependent diabetes mellitus (NIDDM) need to be defined. In preparation for a long-term trial, a feasibility study of 153 men in 5 medical centers compared standard vs intensive insulin therapy. To assess the rate of development of new cardiovascular events and their correlates. Patients with a mean +/- SD age of 60 +/- 6 years and diagnosis of NIDDM for 7.8 +/- 4.0 years were randomly assigned to a standard (1 insulin injection every morning) or to an intensive treatment arm (stepped plan from 1 evening injection of insulin, alone or with glipizide, to multiple daily injections) designed to attain near-normal glycemia levels. A 2.07% separation of glycosylated hemoglobin (HbA1c) was sustained for a mean follow-up of 27 months (P < .001). Predefined cardiovascular events were assessed by a committee unaware of treatment assignment. Mild and moderate hypoglycemic events were more frequent in the intensive than in the standard treatment arm (16.5 vs 1.5 per patient per year, respectively). Mean insulin dose was 23% lower in the standard treatment arm (P < .001). There were 61 new cardiovascular events in 24 patients (32%) in the intensive treatment arm and in 16 patients (20%) in the standard treatment arm (P = .10). There was no difference in total and cardiovascular mortality (n = 5 and n = 3 in the intensive and standard treatment arms, respectively) or in new events in patients with cardiovascular history (n = 10 in each arm). In Cox regression analysis, the only significant correlate for new cardiovascular events was previous cardiovascular disease (P = .04). Entering in the analysis any baseline cardiovascular abnormality, the regression model indicated a lower HbA1c level prior to the event as the only correlate for new cardiovascular events (P = .05). A long-term prospective trial is needed to assess the risk-benefit ratio of intensive insulin therapy for NIDDM in patients who require it.