The role of structured education in the management of hypoglycaemia.

The role of intensive glycaemic control in preventing microvascular disease in diabetes is well established. Iatrogenic hypoglycaemia is, however, a major barrier to effective treatment. Hypoglycaemia is associated with a significant level of morbidity and, despite pharmacological and technological therapeutic advances, reported rates of severe hypoglycaemia in clinical practice have not fallen over the last 20 years. This suggests that human factors are of major relevance and that ensuring the effective self-management of diabetes is an important strategy for the reduction of hypoglycaemic risk. Most of the evidence for the impact of this strategy on hypoglycaemia risk is confined to adults with type 1 diabetes although, in this review, we also cite studies that have specifically addressed this in type 2 diabetes. There are relatively few adequately powered RCTs that have rigorously evaluated the effectiveness of structured education and training programmes on hypoglycaemia; however, the available data suggest a subsequent reduction in severe hypoglycaemia rates of around 50%, a rate reduction that is comparable with that observed following technological interventions. Furthermore, longitudinal observational cohorts support these data, showing similar reductions in rates of hypoglycaemia following structured education. Those who continue to experience recurrent hypoglycaemia and impaired awareness of hypoglycaemia despite education and training in diabetes self-management may benefit from technological interventions and/or interventions that specifically address psychological factors that contribute to hypoglycaemia risk; however, there is urgent need for further research in this area. In the meantime, structured education for effective self-management of diabetes should be part of routine therapy for all those with type 1 diabetes

Hypoglycemia in patient with type 2 diabetes treated with insulin: it can happen

There are many misconceptions about the prevalence and effects of hypoglycemia in people with type 2 diabetes (T2D), including hypoglycemia does not occur or does not have adverse consequences in T2D. This narrative review aims to help dispel these myths. Around 25% of people with T2D taking insulin for >5 years were found to have severe hypoglycemic events, which is comparable to the severe hypoglycemia rate in adults with type 1 diabetes (T1D) diagnosed within 5 years. The total number of hypoglycemic events among insulin-treated T2D, including severe hypoglycemia, is as high or higher than among those with T1D. Recent evidence suggests serious consequences of hypoglycemia may, in some respects, be greater in individuals with T2D, particularly regarding effects on the cardiovascular system. Hypoglycemia is generally patient-reported. Issues with hypoglycemia unawareness, limited glucose testing, limited recall, lack of event logging and fear of failure or shaming limits the number of hypoglycemic episodes reported by people with diabetes. Barriers to healthcare provider inquiry and reporting include lack of knowledge regarding the problem’s magnitude, competing priorities during patient visits, lack of incentives to report and limitations to documentation systems for adequate reporting. All people with diabetes should be encouraged to discuss their experiences with hypoglycemia without judgment or shame. Glucose targets, testing schedules (blood glucose or continuous glucose monitoring) and treatment plans should be reviewed often and individualized to the minimize risk of hypoglycemia. Finally, people with T2D on insulin should always be encouraged to have oral glucose and rescue medication immediately available

Cognitive, behavioural and psychological barriers to the prevention of severe hypoglycaemia: A qualitative study of adults with type 1 diabetes

Objectives: Severe hypoglycaemia affects approximately one in three people with type 1 diabetes and is the most serious side effect of insulin therapy. Our aim was to explore individualistic drivers of severe hypoglycaemia events. Methods: In-depth semi-structured interviews were conducted with a purposive sample of 17 adults with type 1 diabetes and a history of recurrent severe hypoglycaemia, to elicit experiences of hypoglycaemia (symptoms/awareness, progression from mild to severe and strategies for prevention/treatment). Interviews were analysed using an adapted grounded theory approach. Results: Three main themes emerged: hypoglycaemia-induced cognitive impairment, behavioural factors and psychological factors. Despite experiencing early hypoglycaemic symptoms, individuals often delayed intervention due to impaired/distracted attention, inaccurate risk assessment, embarrassment, worry about rebound hyperglycaemia or unavailability of preferred glucose source. Delay coupled with use of a slow-acting glucose source compromised prevention of severe hypoglycaemia. Conclusion: Our qualitative data highlight the multifaceted, idiosyncratic nature of severe hypoglycaemia and confirm that individuals with a history of recurrent severe hypoglycaemia may have specific thought and behaviour risk profiles. Individualised prevention plans are required, emphasising both the need to attend actively to mild hypoglycaemic symptoms and to intervene promptly with an appropriate, patient-preferred glucose source to prevent progression to severe hypoglycaemia

Psychological interventions to improve glycemic control in adults with type 2 diabetes: a systematic review and meta-analysis

The quality of evidence that psychological interventions are effective in improving glycemic control in adults with type 2 diabetes (T2D) is weak. We conducted a systematic review and meta-analysis of psychological interventions in T2D to assess whether their effectiveness in improving glycemic levels has improved over the past 30 years. We applied the protocol of a systematic review and aggregate meta-analysis conducted to January 2003. We added network meta-analysis (NMA) to compare intervention and control group type against usual care. MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, EMBASE, Cochrane Controlled Trials Database, Web of Science, and Dissertation Abstracts International were searched from January 2003 to July 2018. Only randomized controlled trials (RCT) of psychological interventions for adults with T2D reported in any language were included. The primary outcome was change in glycemic control (glycated hemoglobin (HbA1c) in mmol/mol). Data were extracted from study reports and authors were contacted for missing data. 94 RCTs were eligible for inclusion in the systematic review since the last review. In 70 RCTs (n=14 796 participants) the pooled mean difference in HbA1c in those randomized to psychological intervention compared with control group was −0.19 (95% CI −0.25 to −0.12), equivalent to a reduction in HbA1c of 3.7 mmol/mol, with moderate heterogeneity across studies (I2=64.7%, p<0.001). NMA suggested the probability of intervention effectiveness is highest for self-help materials, cognitive–behavioral therapy, and counseling, compared with usual care. Limitations of this study include that there is a possibility that some studies may have been missed if diabetes did not appear in the title or abstract. The effectiveness of psychological interventions for adults with T2D have minimal clinical benefit in improving glycemic control. PROSPERO registration number CRD42016033619

Reducing the burden of hypoglycaemia in people with diabetes through increased understanding:design of the Hypoglycaemia Redefining Solutions for Better Lives (Hypo-RESOLVE) project

Background Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all‐cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of ‘non‐severe’ hypoglycaemia and the glucose level below which hypoglycaemia causes harm. Aim To increase understanding of hypoglycaemia by addressing the above issues over a 4‐year period. Methods Hypo‐RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor‐detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems. Results The outcomes of Hypo‐RESOLVE will inform evidence‐based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose‐lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement. Conclusion Hypo‐RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes

Redefining hypoglycemia in clinical trials: validation of definitions recently adopted by the American Diabetes Association/European Association for the study of diabetes

OBJECTIVE The purpose of this study was to determine if the International Hypoglycemia Study Group (IHSG) level 2 low glucose definition could identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials. RESEARCH DESIGN AND METHODS A post hoc analysis of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE; n = 7,637, type 2 diabetes) using the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2) IHSG level 2 (glucose confirmed <3.0 mmol/L). RESULTS In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition. Similar results were observed for the SWITCH 1 trial. CONCLUSIONS The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials

Cardiac autonomic regulation and repolarization during acute experimental hypoglycemia in Type 2 diabetes

Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in T2DM patients. Our aim was to examine changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and eleven age, BMI-matched nondiabetic controls underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0mmol/L) or hypoglycemia (2.5mmol/L) for one hour. Heart rate, blood pressure, heart rate variability were assessed every thirty minutes and corrected QT (QTc) and T wave morphology every 60 minutes. Heart rate initially increased in T2DM participants but then fell towards baseline despite maintained hypoglycemia at 1 hour, accompanied by reactivation of vagal tone. In nondiabetic participants, vagal tone remained depressed during sustained hypoglycemia. Diabetic participants exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T wave symmetry and Principal Component Analysis (PCA) ratio compared with the nondiabetic group. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears time-dependent. T2DM individuals demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes

Lower rates of hypoglycaemia in older individuals with type 2 diabetes using insulin degludec versus insulin glargine U100 : results from SWITCH 2

Aim This study aimed to investigate the safety of insulin degludec (degludec) in relation to age and risk of hypoglycaemia post hoc in individuals with type 2 diabetes (T2D) (SWITCH 2 trial). Methods In this crossover study, individuals with T2D who were at risk of hypoglycaemia were randomized to double‐blind treatment with degludec or insulin glargine 100 units/mL (glargine U100) ± oral antidiabetic drugs. After 32 weeks, patients crossed over to the other treatment. Primary endpoint was number of overall severe (positively adjudicated) or glucose‐confirmed (plasma glucose <56 mg/dL; 3.1 mmol/L) symptomatic hypoglycaemia events during the two 16‐week maintenance periods. Results For individuals ≤65 (n = 450) and >65 (n = 270) years, baseline median (range) duration of diabetes was 12 (1–40) vs 15 (1–54) years, mean HbA1c was 7.7% vs 7.4% and mean estimated glomerular filtration rate was 87.0 vs 63.7 mL/min/1.73 m2, respectively. No significant differences in HbA1c reduction were seen in individuals ≤65 or >65 years. During both maintenance periods, treatment with degludec lowered rates of hypoglycaemia (overall/nocturnal symptomatic) vs those with glargine U100 in individuals ≤65 (31% vs 43%) and >65 (30% vs 41%) years. With degludec and glargine U100, respectively, six vs nine severe hypoglycaemic events occurred in individuals ≤65 years and four vs eight events occurred in those >65 years. Adverse event rates were 3.2 and 3.3 events/patient‐year for individuals ≤65 years and were 3.5 and 4.1 events/patient‐year for individuals >65 years with degludec and glargine U100, respectively. Conclusion Treatment with degludec was safe and effective, with a frequency of hypoglycaemia lower than that with glargine U100 in both younger and older individuals (>65 years) with T2D