Risk Of Hypoglycemia In People Research Articles

Intermittent closed-loop blood glucose control for people with type 1 diabetes on multiple daily injections

Background and objectives: Recent advances in Automated Insulin Delivery systems have been shown to dramatically improve glycaemic control and reduce the risk of hypoglycemia in people with type 1 diabetes. However, they are complex systems that require specific training and are not affordable for most. Attempts to reduce the gap with closed-loop therapies using advanced dosing advisors have so far failed, mainly because they require too much human intervention. With the advent of smart insulin pens, one of the main constraints (having reliable bolus and meal information) disappears and new strategies can be employed. This is our starting hypothesis, which we have validated in a very demanding simulator. In this paper, we propose an intermittent closed-loop control system specifically intended for multiple daily injection therapy to bring the benefits of artificial pancreas to the application of multiple daily injections.Methods: The proposed control algorithm is based on model predictive control and integrates two patient-driven control actions. Correction insulin boluses are automatically computed and recommended to the patient to minimize the duration of hyperglycemia. Rescue carbohydrates are also triggered to avoid hypoglycemia episodes. The algorithm can adapt to different patient lifestyles with customizable triggering conditions, closing the gap between practicality and performance. The proposed algorithm is compared with conventional open-loop therapy, and its superiority is demonstrated through extensive in silico evaluations using realistic cohorts and scenarios. The evaluations were conducted in a cohort of 47 virtual patients. We also provide detailed explanations of the implementation, imposed constraints, triggering conditions, cost functions, and penalties for the algorithm.Results: The in-silico outcomes combining the proposed closed-loop strategy with slow-acting insulin analog injections at 09:00 h resulted in percentages of time in range (TIR) (70–180 mg/dL) of 69.5%, 70.6%, and 70.4% for glargine-100, glargine-300, and degludec-100, respectively, and injections at 20:00 h resulted in percentages of TIR of 70.5%, 70.3%, and 71.6%, respectively. In all the cases, the percentages of TIR were considerably higher than those obtained from the open-loop strategy, being only 50.7%, 53.9%, and 52.2% for daytime injection and 55.5%, 54.1%, and 56.9% for nighttime injection. Overall, the occurrence of hypoglycemia and hyperglycemia was notably reduced using our approach.Conclusions: Event-triggering model predictive control in the proposed algorithm is feasible and may meet clinical targets for people with type 1 diabetes.

Glycemic control in people with diabetes treated with cancer chemotherapy: contribution of continuous glucose monitoring.

The aim of our study was to assess, with Continuous Glucose Monitoring (CGM), exhaustive information on the glucose profile in people with diabetes starting chemotherapy. We also evaluated the adaptation of glucose-lowering drugs following analysis of CGM recordings. Eighty-five people with diabetes starting chemotherapy were included in the ONCODIAB study. A CGM was worn for up to fourteen days in blinded mode before and after the diabetologist's intervention to evaluate the impact of modifying the glucose-lowering drugs. Time spent in range was 67.2 ± 24.2%. Time below the target glucose range (TBR) (< 70mg/dl) was 8.9% in all the study population. TBR was significantly higher in patients treated with at least one drug due to the risk of hypoglycemia compared to the others (11.5% vs. 4.4%, p = 0.009). Sixty-five patients had available sensor data for the two recordings. Forty-one patients (51.9%) saw a decrease in their antidiabetic treatment after the diabetologist's intervention guided by the first CGM recording. We observed a significant reduction in the time spent below the target glucose range (70-55mg/dl) between the two CGM recordings (10.3 ± 14.6% vs. 6.3 ± 9.4%, p = 0.016 and 3.8 ± 8.4% vs. 1.2 ± 2.9%, p = 0.012, respectively). CGM use in blinded mode could be an interesting tool to reduce the risk of hypoglycemia in people with diabetes starting chemotherapy. Our findings fully support the recommendation that assessing hypoglycemia risk should be mandatory in patients with diabetes before starting chemotherapy.

Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?

Hypoglycemia in people with type 2 diabetes mellitus (T2DM) is troublesome and an important barrier to diabetes management. Although more intensive glycemic control is emphasized to prevent diabetes-related long-term complications, it raises the risk of hypoglycemia in people with T2DM. Severe hypoglycemia (SH), defined as critical events characterized by altered mental and/or physical status requiring assistance for recovery, is considered an advanced and life-threatening form of hypoglycemia. The detection of SH is an important issue because it is associated with further adverse clinical outcomes such as cardiovascular events, mortality, cognitive impairment, and decreased quality of life. By identifying the potential risk factors for SH and introducing measures to minimize SH, SH itself and subsequent harmful clinical outcomes could be prevented in people with T2DM. The traditional risk factors for SH in T2DM, such as older age, long-standing diabetes with decreased insulin secretion, advanced vascular complications, serious comorbidities, and insulin use, are usually unmodifiable. However, unhealthy lifestyle factors, defined as current smoking, heavy alcohol consumption, and lack of regular exercise, can be improved through active patient education. In recent research, greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were found to be associated with a substantially lower risk of SH in individuals with T2DM. As well as being an essential component of diabetes self-care and optimal glycemic control, lifestyle modification probably contributes to the prevention of SH in individuals with T2DM.

58th EASD Annual Meeting from 19 to 23 September 2022, Stockholm, Sweden (Virtual)

AbstractThe 58th European Association for the Study of Diabetes (EASD) Annual Meeting was held between 19 and 23 September 2022 in Stockholm, Sweden. It was also fully streamlined online. The authors attended the conference, giving a narrative commentary on what they felt were the highlights of the meeting. Several interesting lectures were presented. The ADA-EASD hyperglycemia management consensus was among the landmark presentations. The development of a particular model that could predict severe hypoglycemia risk in people with type 2 diabetes (T2D) was interesting. The remission of T2D data from the ReTUNE analysis backs the “personal fat threshold” concept was very promising. Interestingly, a link between autoimmunity degree and latent autoimmune diabetes in adults' cardiovascular disease (CVD) risk was proposed. A benefit of high-intensity exercise for people with impaired hypoglycemia awareness was demonstrated. The CLOuD, namely, early and sustained closed-loop therapy does not stave off β-cell decline, data were shared. Also, subjective energy levels were shown to predict CV events in T2D. Also, C-peptide may be better than C-reactive protein for predicting CV risk in T2D. Furthermore, a fatty liver index may predict mortality and CVD risk in people with T1D. New data suggest that topical esmolol hydrochloride might aid in the healing of diabetic foot ulcers. Finally, microalbuminuria in pregnancy forecasts adverse outcomes. We hope this short account helps those who did not attend the conference to get a glimpse of the program.

Below Which Threshold of Glycemic Variability Is There a Minimal Risk of Hypoglycemia in People with Type 2 Diabetes?

Not applicable for a commentary.

Adherence to antidiabetic treatment and impaired hypoglycemia awareness in type 2 diabetes mellitus assessed in Spanish community pharmacies: the ADHIFAC study

IntroductionAdherence to treatment and hypoglycemia awareness are strongly linked to glycemic control and hypoglycemia risk in people with type 2 diabetes mellitus (T2DM). Community pharmacies are suitable facilities to detect...

Clustering of Hypoglycemia Events in Patients With Hyperinsulinism: Extension of the Digital Phenotype Through Retrospective Data Analysis.

BackgroundHyperinsulinism (HI) due to excess and dysregulated insulin secretion is the most common cause of severe and recurrent hypoglycemia in childhood. High cerebral glucose use in the early hours results in a high risk of hypoglycemia in people with diabetes and carries a significant risk of brain injury. Prevention of hypoglycemia is the cornerstone of the management of HI, but the risk of hypoglycemia at night or the timing of hypoglycemia in children with HI has not been studied; thus, the digital phenotype remains incomplete and management suboptimal.ObjectiveThis study aims to quantify the timing of hypoglycemia in patients with HI to describe glycemic variability and to extend the digital phenotype. This will facilitate future work using computational modeling to enable behavior change and reduce exposure of patients with HI to injurious hypoglycemic events.MethodsPatients underwent continuous glucose monitoring (CGM) with a Dexcom G4 or G6 CGM device as part of their clinical assessment for either HI (N=23) or idiopathic ketotic hypoglycemia (IKH; N=24). The CGM data were analyzed for temporal trends. Hypoglycemia was defined as glucose levels <3.5 mmol/L.ResultsA total of 449 hypoglycemic events totaling 15,610 minutes were captured over 237 days from 47 patients (29 males; mean age 70 months, SD 53). The mean length of hypoglycemic events was 35 minutes. There was a clear tendency for hypoglycemia in the early hours (3-7 AM), particularly for patients with HI older than 10 months who experienced hypoglycemia 7.6% (1480/19,370 minutes) of time in this period compared with 2.6% (2405/92,840 minutes) of time outside this period (P<.001). This tendency was less pronounced in patients with HI who were younger than 10 months, patients with a negative genetic test result, and patients with IKH. Despite real-time CGM, there were 42 hypoglycemic events from 13 separate patients with HI lasting >30 minutes.ConclusionsThis is the first study to have taken the first step in extending the digital phenotype of HI by describing the glycemic trends and identifying the timing of hypoglycemia measured by CGM. We have identified the early hours as a time of high hypoglycemia risk for patients with HI and demonstrated that simple provision of CGM data to patients is not sufficient to eliminate hypoglycemia. Future work in HI should concentrate on the early hours as a period of high risk for hypoglycemia and must target personalized hypoglycemia predictions. Focus must move to the human-computer interaction as an aspect of the digital phenotype that is susceptible to change rather than simple mathematical modeling to produce small improvements in hypoglycemia prediction accuracy.

Risk of hypoglycemia in Japanese people with type 2 diabetes mellitus who initiated or switched to insulin glargine 300 U/mL: A subgroup analysis of 12-month post-marketing surveillance study (X-STAR study)

AimsThis study investigated the hypoglycemia risk in people with type 2 diabetes (T2D) who initiated or switched to insulin glargine 300 U/mL (Gla-300) by stratifying them by age and renal function. MethodsWe examined data from 4621 people with T2D (1227 insulin-naïve and 3394 insulin-experienced) of the X-STAR study, a prospective, observational, 12-month study conducted from December 2015 to August 2018 in Japan. Participants were stratified by age (<65, 65 to <75, and ≥75 years) and estimated glomerular filtration rate (eGFR) (≥90, 60 to <90, 30 to <60, and <30 mL/min/1.73 m2). Hypoglycemia was defined according to the Ministry of Health, Labour and Welfare manual of Japan. ResultsNo apparent increase in the proportion of people who experienced hypoglycemia was found in all subgroups. The proportions were 2.9–3.5% and 2.7–5.2% of insulin-naïve and insulin-experienced people, respectively, for age subgroups, and 2.4–4.7% and 4.6–4.8%, respectively, for eGFR subgroups. The result was similar for HbA1c levels below and at or above 7.0% in all age subgroups. ConclusionsOur study found no apparent increase in the hypoglycemia risk in people with older age and renal impairment who were administered Gla-300. These results would provide reassuring information on Gla-300 use.

An Evaluation of the Safety of Pilots With Insulin-Treated Diabetes in Europe Flying Commercial and Noncommercial Aircraft.

The risk of hypoglycemia in people with insulin-treated diabetes has debarred them from certain "safety-critical" occupations, including flying commercial aircraft. This report evaluates the effectiveness of a protocol enabling a large cohort of insulin-treated pilots to fly commercially. This was an observational study of pilots with insulin-treated diabetes who were granted medical certification to fly commercial and noncommercial aircraft. Clinical details, pre- and in-flight (hourly and 30 min before landing) blood glucose values were correlated against the protocol-specified ranges: green (5-15 mmol/L), amber (low, 4-4.9 mmol/L; high, 15.1-20 mmol/L), and red (low, <4 mmol/L; high, >20 mmol/L). A total of 49 pilots with type 1 (84%) or type 2 (16%) diabetes who had been issued class 1 or class 2 certificates were studied. Median diabetes duration was 10.9 years. Mean HbA1c was 7.2% (55.0 mmol/mol) before certification and 7.2% (55.1 mmol/mol) after certification (P = 0.97). Blood glucose values (n = 38,621) were recorded during 22,078 flying hours. Overall, 97.69% of measurements were within the green range, 1.42% within the low amber range, and 0.75% within the high amber range. Only 0.12% of readings were within the low red range and 0.02% within the high red range. Out-of-range readings declined from 5.7% in 2013 to 1.2% in 2019. No episodes of pilot incapacitation occurred, and glycemic control did not deteriorate. The protocol is practical to implement, and no events compromising safety were reported. This study represents what is, to our knowledge, the most extensive data set from people with insulin-treated diabetes working in a "safety-critical" occupation, which may be relevant when estimating risk in other safety-critical occupations.

Fasting insulin levels correlate with the frequency of hypoglycemic events in people with type 2 diabetes on treatment with sulfonylureas: A pilot study.

AIMS AND OBJECTIVES:We aimed to explore whether fasting insulin levels correlate with the risk of hypoglycemia in people with Type 2 diabetes (T2D) receiving sulfonylureas (SUs).MATERIALS AND METHODS:Our study included 58 individuals with T2D who had been on treatment with SUs, but not insulin, for more than 2 years. Confirmed hypoglycemic episodes during the past year were self-reported by the patients, and a potential relationship of hypoglycemic event frequency with fasting insulin levels was investigated.RESULTS:Fasting insulin concentrations were found to have a low positive and statistically significant correlation with the number of cases of mild hypoglycemia per year (ρ = 0.279/P = 0.034) and a moderately positive and statistically significant correlation with the number of severe hypoglycemic events per month (ρ = 0.349/P = 0.007) and per year (ρ = 0.39/P = 0.002).CONCLUSION:Our results suggest that fasting insulin levels might be a predictor of the risk of hypoglycemia in people with T2D on treatment with SUs.

A brief interactive training with medical students improves their diabetes knowledge about hypoglycemia

BackgroundHypoglycemia is a severe clinical problem with physical and psychosocial implications for people with type 1 and type 2 diabetes. Medical students would benefit from formal education on how to treat hypoglycemia as well as how to administer glucagon in case of a severe hypoglycemic emergency. The purpose of this study was to assess the effectiveness of a brief training to improve medical students’ knowledge and attitudes about diabetes, hypoglycemia, and glucagon administration.MethodsWe conducted a feasibility study to assess the effectiveness of an interactive training session on diabetes education with an emphasis on hypoglycemia. We measured medical students’ knowledge and attitudes toward diabetes, hypoglycemia, and glucagon before and after the training. We performed Chi-Square tests, paired t-tests, determined effect sizes using Cohen’s d, and analyzed short answer responses via content and thematic analyses.ResultsTwo hundred and seventeen participants (age = 25.1 ± 2.3 years, 45.2% female, 78.3% white, 36.4% planned to pursue primary care, response rate of 94.3%) completed surveys. Following the training, participants’ total knowledge scores improved by five percentage points to 82.6 ± 11.0% (t-value = 7.119, p < 0.001). We also observed positive improvements in the General Test scores to 82.3 ± 12.6% (t-value = 5.844, p < 0.001) and Insulin Use Test scores to 82.4 ± 17.4% (t-value = 4.103, p < 0.001). For the hypoglycemia test, participants averaged 55.7 ± 24.8% pre-training and 83.0 ± 22.4% post-training (t-value = 14.258, p < 0.001). Lastly, participants scored 87.6 ± 18.5% on the glucagon test after the training session. In addition, we observed positive improvements in all five diabetes attitudes subscales after the training, with the largest magnitude of change in the “Psychosocial impact of diabetes” subscale (t-value = 9.249, p < 0.001, Cohen’s d = 0.60). Qualitatively, more participants recognized the severity of hypoglycemia after the training. They also learned how to approach diabetes from the patient’s perspective and valued the clinically relevant and practical information provided during the training session, such as the “15–15 Rule.”ConclusionsMedical students need to learn about patients’ everyday experiences of diabetes in order to have an understanding of and confidence to assess and treat hypoglycemia. These findings underscore the importance of training medical students on how to actively assess and manage the risk of hypoglycemia in people with diabetes.

Plasma C-Peptide Concentration and Risk of Hypoglycemia in People with T2DM treated with Insulin Glagine 300 U/mL (Gla-300) or Insulin Glargine 100 U/mL (Gla-100)

Risk of hypoglycaemia on insulin treatment increases as B-cell function progressively deteriorates in Type 2 diabetes. Using data from the EDITION 1, 2 and 3 treat-to-target trials in T2DM, we analyzed baseline fasting plasma C-peptide concentration and hypoglycemia during 6 months treatment with Gla-300 vs Gla-100 to explore if C-peptide was associated with hypoglycemia risk. C-peptide levels <0.4 nmol/L were more frequent in previously insulin-treated participants in EDITION 1and 2 trials (54%) compared with the insulin-naïve in EDITION 3 (12.5%). Comparable numbers of participants treated with Gla-300 or Gla-100 had lower C-peptide (EDITION 1, 221 vs 209; EDITION 2, 207 vs 216; EDITION 3, 52 vs 43).

Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes.

To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. A total of 72 people [46 men, mean±sd age 54 ± 12years, mean±sd HbA1c 65±12mmol/mol (8.1±1.1%), mean±sd duration of diabetes 30±14years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn hourly during sleep. Primary endpoints were nocturnal glucose profiles and occurrence of hypoglycaemia (blood glucose≤3.9mmol/l). During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P<0.0001) with insulin analogue. Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia.

Hypoglycaemia, a global cause for concern

Hypoglycaemia in diabetes is often considered to be relevant only to those with type 1 diabetes T1D. Evidence has long been available that hypoglycaemia occurs in people with type 2 diabetes (T2D) using sulphonylureas. (Episodes will be more prolonged than with insulin alone.) However, the risk of hypoglycaemia in people with T2D has received little attention with the implication that it can be ignored.

Diabetes and alcohol

Diabetes and alcohol

The extra‐pancreatic effects of GLP‐1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta-cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP-1 receptors are also expressed in extra-pancreatic tissues and trial data suggest that GLP-1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP-1 or GLP-1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP-1RAs in both people with type 2 diabetes and obese people without diabetes. GLP-1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP-1RA-induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP-1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra-pancreatic effects of GLP-1RAs could provide multi-factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP-1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP-1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future.

Meta‐analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine

To estimate absolute and relative incidence rates of hypoglycaemia when using once-daily evening or morning regimens of insulin glargine (glargine) versus once-daily evening NPH insulin (NPH) using individual patient data (IPD). Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or NPH once-daily (with oral glucose-lowering drugs) were identified. Two study pools were analysed: evening glargine versus evening NPH (pool 1); and morning glargine versus evening NPH (pool 2). The number-needed-to-treat to avoid hypoglycaemia was calculated for glargine versus NPH. In study pool 1 (n = 2711), the risk of nocturnal hypoglycaemia was approximately halved with glargine compared with NPH [odds ratios (OR): 0.44-0.52, p < 0.001-0.047]. This led to a significant reduction in anytime risk of symptomatic hypoglycaemia [plasma glucose (PG) <3.9 mmol/l, OR: 0.64, p = 0.018; PG <2.0 mmol/l, OR: 0.51, p < 0.001]. In study pool 2 (n = 470), although a strong numerical reduction in all types of nocturnal hypoglycaemia was observed (OR: 0.16-0.64), statistical significance was reached only for symptomatic hypoglycaemia with PG <3.9 mmol/l (p < 0.001). Eight (pool 1) or five (pool 2) people with T2DM needed to use glargine rather than NPH to avoid one person from experiencing a nocturnal symptomatic hypoglycaemic event within a median of about 25 weeks of starting insulin. This meta-analysis of open-label studies provides confidence that reductions of around 50% of risk for nocturnal hypoglycaemia can be achieved with using glargine instead of NPH.

Determining the risk of hypoglycaemia in people with type 2 diabetes: an approach for clinical practice

Hypoglycaemia and its consequences are a significant risk for many people who have type 2 diabetes, yet it is often under-recognised, and may be avoidable. Severe hypoglycaemic events have an impact on mortality, morbidity and quality of life of many people with type 2 diabetes. With current clinical guidelines recommending strict glycaemic control, it is likely that the clinical risk of hypoglycaemia will increase, such that better recognition of the symptoms of hypoglycaemia is increasingly important in order to reduce the risk of progression to more severe episodes. This article outlines a series of structured questions which may be useful in eliciting an accurate account of the frequency and severity of hypoglycaemic events.

ACE Inhibitors and Risk of Hypoglycemia in People With Diabetes

ACE Inhibitors and Risk of Hypoglycemia in People With Diabetes