Impact of Pharmacist-Led Deprescribing on Inappropriate Rapid-Acting Insulin Use Among Admitted Older Adults

Hypoglycemia and the predisposition to cardiovascular disease: Is the pro-inflammatory-pro-coagulant diathesis a plausible explanation?

Type 1 Diabetes in Children and Adolescents

Aims/hypothesisPhysical activity increases the risk of hypoglycaemia in individuals with type 2 diabetes when basal or basal-bolus insulin therapy is administered. Once-weekly basal insulins may elevate the risk of physical activity-attributed hypoglycaemia compared with other basal insulins because the administered levels cannot be reduced in anticipation of increased physical activity. This post hoc analysis of five separate randomised trials (ONWARDS 1–5) aimed to examine physical activity-attributed hypoglycaemic episodes in adults with type 2 diabetes receiving either once-weekly basal insulin icodec (herein referred to as ‘icodec’) or once-daily basal insulins.MethodsThe ONWARDS 1–5 Phase 3a randomised controlled trials compared the efficacy and safety of once-weekly basal icodec vs once-daily basal insulin in insulin-naive (ONWARDS 1, 3 and 5) and insulin-experienced (ONWARDS 2 and 4) adults with type 2 diabetes. Participants self-monitored their blood glucose levels using a blood glucose meter and a digital diary. In each trial, suspected hypoglycaemia symptoms triggered additional self-measured blood glucose readings, and values indicative of hypoglycaemia were recorded in the participants’ digital diary. Participants who experienced hypoglycaemic episodes were instructed to note any relation of each episode to physical activity. Hypoglycaemic episodes were classified as alert value (level 1: blood glucose <3.9 but ≥3.0 mmol/l), clinically significant (level 2: blood glucose <3.0 mmol/l) or severe (level 3: cognitive impairment requiring external assistance). The proportions of hypoglycaemic episodes that were attributed to physical activity and the ORs of having a physical activity-attributed hypoglycaemic episode were calculated for the two basal insulin types (once-weekly vs once-daily) for each of the five trials.ResultsAcross all trials, there were no consistent differences between icodec and the once-daily insulin comparators in the proportions of hypoglycaemic episodes that were attributed to physical activity; these episodes were mainly alert value or clinically significant hypoglycaemic episodes. In both insulin-naive and insulin-experienced participants, the incidence of physical activity-attributed clinically significant or severe hypoglycaemic episodes was consistently ≤3.0% in ONWARDS 1, 2, 3 and 5. In ONWARDS 4, the incidence of physical activity-attributed hypoglycaemic episodes was numerically higher in both treatment groups (18.6% [icodec] vs 17.9% [insulin glargine U100]), which was expected given the basal-bolus insulin regimen. Across all trials, there were no statistically significant differences in the odds of experiencing a physical activity-attributed clinically significant or severe hypoglycaemic episode with icodec vs once-daily insulin comparators. The frequency of recurrent clinically significant or severe hypoglycaemic episodes in the 24 h after a physical activity-attributed clinically significant or severe hypoglycaemic episode was low, with no such episodes in ONWARDS 1, 3 and 5. In contrast, in ONWARDS 2 and 4, the frequency of recurrent clinically significant hypoglycaemic episodes in the 24 h after a physical activity-attributed clinically significant or severe hypoglycaemic episode was numerically higher with icodec vs the once-daily insulin comparators, whilst no additional severe episodes were reported in any participants across the trials.Conclusions/interpretationThese findings do not suggest that there is an additional increase in hypoglycaemia risk attributed to physical activity with once-weekly basal icodec vs once-daily basal insulins in adults with type 2 diabetes.Trial registrationClinicalTrials.gov NCT04460885 (ONWARDS 1), NCT04770532 (ONWARDS 2), NCT04795531 (ONWARDS 3), NCT04880850 (ONWARDS 4) and NCT04760626 (ONWARDS 5).Graphical

IntroductionInnovative approaches are needed to design robust clinical decision support (CDS) to optimize hospital glycemic management. We piloted an electronic medical record (EMR), evidence-based algorithmic CDS tool in an academic...

Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

To investigate the trajectory in glycemic control following episodes of severe hypoglycemia (SH) among children and adolescents with type 1 diabetes (T1D). A Danish national population-based study comprising data from 2008-17. SH was defined according to the 2014 ISPAD guidelines. A mixed model was applied with HbA1c as outcome and SH episodes and time since first episode as explanatory variables. Data were adjusted for age, gender and diabetes duration. A total of 4244 children (51.6% boys) with 18 793 annual outpatient visits were included. Mean (SD) age at diabetes onset was 9.0 (4.1) years. Median diabetes duration at inclusion in the study was 1.2 (Q1 = 0.9, Q3 = 3.0) years, and median diabetes duration at last visit was 5.0 (Q1 = 2.7, Q3 = 8.1) years. A total of 506 children experienced at least one episode of SH during the nine-year follow-up; 294 children experienced one episode, 115 two episodes and 97 three or more episodes of SH. HbA1c increased with episodes of SH and in the years following the first episode. The glycemic trajectory peaked 2 to 3 years after an SH episode. The accumulated deterioration in glycemic control was in the range of 5% in patients with two or more episodes equivalent to an increase in HbA1c of 4 mmol/mol (HbA1c ~0.4%). SH was followed by a progressive and lasting increase in HbA1c among Danish children and adolescents with T1D. Thus, in addition to the known risk of new episodes of hypoglycemia and cognitive impairment, SH contributes to long-term diabetes complications.

New Medications for the Treatment of Diabetes.

Type 1 Diabetes in Children and Adolescents.

Evaluación de un protocolo de perfusión continua de insulina en enfermos críticos

To determine the hypo- and hyperglycemic outcomes associated with implementing the American Geriatrics Society (AGS) guideline for a glycosylated hemoglobin (HbA1c) level of less than 8% in frail older adults with diabetes mellitus (DM). Guideline implementation. Program of All-Inclusive Care for the Elderly. All participants in the before (October 2002-December 2004, n=338), early (January 2005-June 2006, n=289) and late (July 2006-December 2008, n=385) periods of guideline implementation with a diagnosis of DM and at least one HbA1c measurement. Clinician education in 2005 with annual monitoring of the proportion of each clinician's patients with DM with HbA1c less than 8%. Hypoglycemia (blood glucose<50 mg/dL), hyperglycemia (blood glucose>400 mg/dL), and severe hypoglycemia (emergency department (ED) visit for hypoglycemia). Participants in the before, early, and late periods were similar in age, race and ethnicity, comorbidities, and functional dependence. Antihyperglycemic medication use was greater in the late period, with more participants using metformin (28% before, 42% late, P<.001) and insulin (23% before, 34% late, P<.001) and achieving the AGS glycemic target of HbA1c of less than 8% (74% before, 84% late, P<.001). Episodes of hyperglycemia (per 100 person-years) were dramatically lower in the late period (159 before, 46 late, P<.001), and episodes of hypoglycemia were similar (10.1 before, 9.3 late, P=.50). There were more episodes of severe hypoglycemia in the early period (1.1 before, 2.9 early, P=.03). Implementing the AGS glycemic control guideline for frail older adults led to fewer hyperglycemic episodes but more severe hypoglycemic episodes requiring ED visits in the early implementation period. Future glycemic control guideline implementation efforts should be coupled with close monitoring for severe hypoglycemia in the early guideline implementation period.

Hypoglycaemic episodes in patients with type 2 diabetes – risk factors and associations with patient-reported outcomes: The PANORAMA Study

I ndividuals with diabetes, their families, and health care providers (HCPs) often cite hypoglycemia as the limiting factor to achieving optimal diabetes control. Hypoglycemia is a reality for people with type 1 diabetes and for many with type 2 diabetes. According to Cryer,1 the average person with type 1 diabetes suffers two episodes of hypoglycemia per week and one episode of severe hypoglycemia per year. Severe hypoglycemia is less common in those with type 2 diabetes. However, in the U.K. Prospective Diabetes Study (UKPDS), 0.7% per year of patients taking a sulfonylurea and 2.3% per year of those using insulin experienced severe hypoglycemia. Among patients with type 2 diabetes, the greatest frequency of hypoglycemia is found in those on insulin.2 The body's normal response to hypoglycemia is significantly altered in diabetes, as well as by the use of exogenous insulin or insulin secretagogues. Thus, the physiological symptoms and negative consequences of hypoglycemia may result in significant fear of hypoglycemia and anxiety associated with possible hypoglycemia for individuals with diabetes.3 In addition, HCPs may not intensify therapy for fear of inducing hypoglycemia.4 Hypoglycemia has been noted as the limiting factor for many patients in achieving euglycemia. Yet, pivotal studies such as the UKPDS and the Diabetes Control and Complications Trial leave no doubt that improved glycemic control prevents or delays microvascular complications and may also reduce macrovascular events.2,5 Therefore, HCPs and patients alike must seek to achieve euglycemia while limiting hypoglycemia. The risk of hypoglycemia should not be used as an excuse for less-than-optimal glucose control. A glucose level of < 70 mg/dl is generally accepted as the glucose alert level at which individuals with diabetes should take action. The American Diabetes Association (ADA) Workgroup on Hypoglycemia did not define hypoglycemia as it traditionally …

Continuous interstitial glucose monitoring (CGM) is used to assess glycaemic status in some adults and older children with diabetes.1, 2 Additionally, CGM has been used in term, preterm and low birthweight newborns to evaluate glucose concentrations during the first days of life,3 to evaluate efficacy of dextrose gel in preventing hypoglycaemia,4 or to detect episodes of low glucose, which would go unrecognised with standard, intermittent blood sampling.3, 4 CGM could potentially decrease the number of invasive capillary samplings.5 In the current study, the efficacy of CGM in maintaining glucose within a specified range was investigated. Overall, the intervention arm spent more time within the target range (94%) compared to the standard group (84%) or a total of 13 more hours. Although not statistically significant, more infants in the intervention group (15% vs. 12%) experienced at least one episode of hypoglycaemia (glucose = 2.2–2.6 mmol/L) with 13% in the intervention group versus 7% in the standard group having at least one episode of severe hypoglycaemia (glucose <2.2 mmol/L), consistent with previous studies showing that hypoglycaemic episodes might go unnoticed if relying solely on intermittent sampling. Alternatively, the different incidence of hypoglycaemia could be explained by higher rate of insulin use in the intervention arm (61%) compared to the standard group (37%) and a post hoc analysis of infants receiving insulin might have clarified this possibility. The intervention group had less continuous episodes longer than one hour with sensor glucose <2.6 mmol/L and less time in the hyperglycaemic range. The use of CGM was safe regarding episodes of infection or discomfort. The protocol's6 recommendation to start or increase the insulin dose when glucose levels reach 8 mmol/L might explain why more infants in the intervention arm received insulin in the first week of life compared with the standard group. The total dose of insulin was similar between groups, raising the possibility that infants in the intervention arm might have received insulin for transient elevated glucose levels. Different glucose thresholds and different durations of elevated levels before starting insulin might change the impact of CGM on insulin exposure. One interesting exploratory finding was a higher incidence of NEC in the standard group, possibly due to more time spent in the hyperglycaemic range. This deserves further investigation. The authors did not mention the proportion of growth restricted (IUGR) or small for gestational age infants. It is worth considering whether IUGR or other subgroups of infants with increased glycaemic variability in the first week of life (infants of diabetic mothers, congenital infections and HIE) would have demonstrated a different efficacy of CGM. This study adds to the mounting evidence that CGM in preterms used to achieve glycaemic control is safe and efficacious. It extends the results from previous smaller studies to a larger, multicentre one. The optimal glucose concentration target range for preterms was not addressed. However, the results show that CGM can be used to improve future studies investigating different target glucose ranges in relationship to short- and long-term outcomes. Dr. Rozance has received a StatStrip Glucose Meter from Nova Biomedical for use in his research laboratory. https://ebneo.org/preterm-continuous-glucose-monitoring

This study quantifies blood glucose (BG) disturbances occurring before and after episodes of severe hypoglycemia (SH). For 6-8 months, 85 individuals with type 1 diabetes and a history of SH (age, 44+/-10 yr; 41 women and 44 men; duration of diabetes, 26+/-11 yr; hemoglobin A1c, 7.7+/-1.1%) used Lifescan One Touch BG meters for self-monitoring three to five times daily and recorded the date and time of SH episodes in diaries. For each subject, the timing of SH episodes was located in the temporal stream of SMBG readings recorded by the meter, and characteristics, including the Low BG index (LBGI), were computed in 24-h increments. In the 24-h period before the SH episode LBGI rose (P < 0.001), average BG was lower (P = 0.001), and BG variance increased (P = 0.001). In the 24 h after SH, LBGI and BGvariance remained elevated (P < 0.001), but average BG returned to baseline. These disturbances disappeared in 48 h. On the basis of LBGI we identified subjects at low, moderate, and high risk of SH, who reported, on the average, 1.7, 3.4, and 7.4 SH episodes (P < 0.005) during the study. In addition, we designed an algorithm that predicted 50% of all SH episodes that occurred in this subject group. We conclude that episodes of SH are preceded and followed by quantifiable BG disturbances, which could be used to devise warnings of imminent SH.

Severe Hypoglycemia Monitoring and Risk Management Procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial