Hypoglycaemia In Insulin-treated Patients Research Articles

Frequency of Hypoglycemia in Insulin-Treated Patients of Type 2 Diabetes Mellitus

Objective: Our study was designed to explore the frequency of hypoglycemia events in type 2 diabetic patients. We further aimed to correlate the hypoglycemia events with treatment regimes and diabetes duration. Place and Duration: Mayo Hospital Endocrine Outpatient Department. From 1-04-2022 to 30-06-2022. Study type: Clinical based study Methodology: We used the already tested questionnaire from the American Diabetes Association and The Endocrine Society to collect the relevant information. The questionnaire was translated into the local language to facilitate the interview. Copies of the questionnaire were distributed to 1000 patients at the study site. The questionnaire was based on socio-demographic and clinical information including gender, age, duration of diabetes, treatment, frequency of hypoglycemia events, and symptoms. Chi-square was used to analyze the association of risk factors. While odd ratios were also computed at a 95% confidence interval. P-value <0.05 was considered for statistical significance. Results: Total of 360 cases T2DM had hypoglycemic events with a prevalence of 36%. The mean age of patients was reported as 51 years. A total of 200 cases were found in the mentioned age group with a 55.56% prevalence. Elderly age patients were also the secondary target of hypoglycemia with a prevalence ratio of 27.78%. Out of these 360 patients, 320 (86.11%) had mild to moderate hypoglycemia with symptoms of eye tarnishing, tremors, numbness of the tongue, and drowsiness while 15% of cases lost their consciousness and were categorized as severe events of hypoglycemia. Conclusion: The study concluded on a note that insulin-treated patients should be aware of the hypoglycemia events because in these cases the risk is comparatively high than in others. Keywords: Diabetes mellitus, Insulin, Hypoglycemia

Scientific advisory on nocturnal hypoglycemia in insulin-treated patients with diabetes: Recommendations from Indian experts

IntroductionInsulin is one of the commonly prescribed glucose lowering agents in diabetes. Hypoglycemia is the most common complication, and severe hypoglycemia is the most serious complication of insulin therapy. Almost half of all severe hypoglycemia episodes (HEs) occur at night. However, patients are often unaware of their nocturnal hypoglycaemia (NH) risk. Additionally, both healthcare professionals and patients find it difficult to manage NH. The purpose of this expert group meeting is to improve NH awareness and provide guidance for the physicians to recognize and manage NH. MethodThe panel of experts in an e-board deliberated extensively upon the available literature and guidelines on hypoglycemia and NH discussed the consensus on definition, detection, reporting, monitoring, treatment, and optimization of therapy in NH. Result& Conclusion: Though there are many guidelines on the management of HEs in patients with diabetes, very few touch the topic of NH. This scientific advisory on management of NH in insulin treated patients with diabetes is formulated to address this gap in understanding regarding management of NH. The experts provide recommendations for the nocturnal window, defining NH based on blood glucose values, recognition, prevention and management of NH.

An exploratory clinical trial on the efficacy and safety of glucagon-like peptide-1 receptor agonist dulaglutide in patients with type 2 diabetes on maintenance hemodialysis

BackgroundDulaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). However, the efficacy and safety of dulaglutide remain unclear in insulin-treated patients with T2DM on maintenance hemodialysis (HD).MethodsDulaglutide treatment was initiated, and the insulin dose was adjusted according to the needs of individual participants. Primary outcomes were changes in the mean and standard deviation (SD) of blood glucose (BG) levels and mean amplitude of glycemic excursions (MAGE) evaluated by continuous glucose monitoring (CGM) for six days, glycated albumin (GA), glycated hemoglobin (HbA1c), pre-dialysis blood glucose levels, and daily total insulin dose from the baseline over 24 weeks. Secondary outcomes were changes in treatment satisfaction and QOL levels from the baseline, measured by using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Diabetes Therapy-Related Quality of Life questionnaire (DTR-QOL) scores.ResultsThe analysis was performed on the 12 participants who completed the study. The GA level (median − 1.8 [interquartile range − 6.6, − 0.3] %; p = 0.026) and daily total insulin dose (− 15.0 [− 24.5, − 9.4] U/day; p = 0.002) significantly decreased without increasing hypoglycemia (area over the glucose curve < 70 mg/dL: 0.0 [− 0.2, 0.0] mg·24 h/dl; p = 0.917). Four patients successfully withdrew from insulin therapy. The levels of HbA1c, SD of BG, and MAGE showed a decreasing tendency, but no significant improvement. Regarding treatment satisfaction and QOL, the total scores of DTSQ (8.0 [0.3, 12.5]; p = 0.041) and DTR-QOL (15.5 [− 1.8, 42.0]; p = 0.023) significantly improved.ConclusionDulaglutide may help improve glycemic control, treatment satisfaction, and QOL without increasing hypoglycemia in insulin-treated patients with T2DM on maintenance HD.Trial registration This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on October 11, 2016 (registration ID, UMIN000024283).

377-P: Exercise-Related Hypoglycemia Induces Hypercoagulable Changes in Patients with Type 1 Diabetes

Diabetes is a hypercoagulable state predisposing to cardiovascular disease. Physical exercise can improve cardiovascular health but may also cause hypoglycemia in insulin-treated patients. We compared hemostatic profiles of patients with type 1 diabetes (T1D) with healthy controls and delineated hemostatic changes of hypoglycemia, induced with or without exercise, in patients with T1D. Thromboelastography (TEG®6s) was used to compare hemostatic profiles of patients with T1D (N=15, (mean±SD) age 29.4±8.1 years, HbA1c 6.8±0.5%, diabetes duration 13.1±6.2 years, BMI 23.7±2.0 kg/m2) with individually matched healthy controls (N=15) . In addition, the patients with T1D underwent (randomized, crossover design) two separate hyperinsulinemic euglycemic-hypoglycemic clamp days. During decline in plasma glucose and the initial 15 min of hypoglycemia, the subjects were either resting or performing moderate-intensity exercise. TEG was performed at baseline euglycemia and after 15 min and 60 min of hypoglycemia. Compared with healthy controls, patients with T1D were more hypercoagulable with shorter R-time (P&amp;lt;0.001) and K-time (P=0.019) and an increased Angle-value (P=0.009) . Clot maximum amplitude (MA) , functional fibrinogen (MA-FF) , and fibrinolysis (LY-30) were similar in the two groups. In patients with T1D, exercise-related hypoglycemia induced hypercoagulable changes with decreased K-time (P=0.005) , increased Angle-value (P=0.049) , and increased MA (P&amp;lt;0.001) after 15 min of hypoglycemia. These changes were not compensated by an increased fibrinolysis. In contrast, hypoglycemia induced at rest resulted in decreased K-time (P=0.03) and increased MA-FF (P=0.02) only after 60 min, along with increased LY-30 (P=0.02) . In conclusion, patients with T1D have a more hypercoagulable profile than healthy controls, and exercise-related hypoglycemia induces coagulation without a compensatory fibrinolytic activity, which may increase susceptibility for thrombosis. Disclosure P.G.Hagelqvist: None. A.Andersen: n/a. K.Maytham: None. S.Engberg: Employee; Novo Nordisk A/S. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. P.I.Johansson: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. Funding Independent research fund Denmark (1030-00256B) Grosserer L.F. Foghts Fund (21.761)

New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

Hypoglycaemia assessment tool (HAT) study: subanalysis of the Lebanese cohort.

Diabetic hypoglycaemia affects medication adherence, patients' productivity and quality of life. It is also associated with an increased risk of cardiovascular complications. To examine the impact of hypoglycaemia in insulin-treated patients in the Lebanese cohort of the Hypoglycaemia Assessment Tool (HAT) study. The HAT study was an observational study covering a 6-month retrospective and a 4-week prospective period in 24 countries including Lebanon. Data were collected using self-assessment questionnaires and patient diaries from 1158 invited lebanese patients, aged ≥ 18 years, with type 1 or type 2 diabetes mellitus (T1DM/T2DM) treated with insulin for > 12 months. The primary endpoint was the proportion of patients experiencing ≥ 1 hypoglycaemic event during the 4-week follow-up period. After 4 weeks of follow-up, 177/225 [78.7%; 95% confidence interval (CI): 72.7-83.8] of patients with T1DM and 291/630 (46.2%; 95% CI: 42.2-50.2) patients with T2D experienced at least 1 hypoglycaemic event. Rates of nocturnal and severe hypoglycaemia were 10.7 (95% CI: 9.1-12.3) and 13.2 (95% CI: 11.5-14.9) events/patient-year for T1DM, and 3.3 (95% CI: 2.8-3.8) and 4.2 events/patient-year (95% CI: 3.6-4.8) for T2DM, respectively. Fear of hypoglycaemia was significantly associated with nocturnal and severe hypoglycaemia in both diabetes types (P < 0.001). The results suggest that the less-advanced healthcare systems in Lebanon are implicated in lower levels of patient knowledge about hypoglycaemia and related preventive measures. Treatment strategies and glycaemia goals should be individualized according to patient preference, medical benefits, and risk of hypoglycaemia.

Self-reported hypoglycaemia in insulin-treated patients with diabetes mellitus: results from the Singapore cohort of the International Operations Hypoglycaemia Assessment Tool study.

Hypoglycaemia constitutes a significant barrier to achieving glycaemic control with insulin in both Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM). The International Operations Hypoglycaemia Assessment Tool (IO HAT) study was designed to determine the incidence of hypoglycaemia in insulin-treated patients with T1DM and T2DM. The IO HAT study retrospectively and prospectively assessed the incidence of hypoglycaemia in patients with insulin-treated diabetes mellitus in nine countries. This sub-analysis included patients from Singapore with T1DM or T2DM who were aged ≥ 21 years and had completed two self-assessment questionnaires (SAQ1 and SAQ2). Of the 50 T1DM and 320 T2DM patients who completed the SAQ1, 39 T1DM and 265 T2DM patients completed SAQ2; 100% and 90.9%, respectively, experienced at least one hypoglycaemic event prospectively. The incidence rates of any hypoglycaemia were 49.5 events per patient-year (EPPY) and 16.1 EPPY for T1DM and T2DM patients, respectively, in the four-week prospective period. Hypoglycaemia rate did not differ in terms of glycated haemoglobin level. The vast majority of T1DM or T2DM patients (92.0% and 90.7%, respectively) knew the overall definition of hypoglycaemia before study participation, although over half of the patients (T1DM 54.0%, T2DM 51.9%) defined hypoglycaemia based only on symptoms. High proportions of insulin-treated patients with diabetes mellitus in Singapore reported hypoglycaemic events prospectively, showing that they had underreported hypoglycaemic episodes retrospectively. Patient education can help in improving hypoglycaemia awareness and its management in the region.

Intranasal versus injectable glucagon for hypoglycemia in type 1 diabetes: systematic review and meta-analysis.

Glucagon is used to resolve severe hypoglycemia in unconscious patients with diabetes, requiring third-party assistance. A few studies have shown that intranasal (IN) glucagon causes resolution of hypoglycemia in insulin-treated patients with type 1 (T1DM) diabetes. This systematic review and meta-analysis updates the comparison of the effectiveness of IN glucagon with injected intramuscular/subcutaneous (IM/SC) glucagon in treatment of hypoglycemia in T1DM. Controlled randomized studies were considered; eight studies, published in English, were included in a meta-analysis (random-effects model). Intervention effect (resolution of hypoglycemia) was expressed as odds ratio (OR), with 95% confidence intervals. Meta-regression was employed to correlate the effect with size of studies, age of patients, basal blood glucose levels. In a total of 467 treatments in 269 patients with IN and IM/SC glucagon, the OR IN versus IM/SC was 0.61 (CI 0.13-2.82); since four of eight studies showed 100% effectiveness, a simulation was made with 1 failure for each treatment; in this simulation analysis, the OR was 0.80 (95% CI 0.28-2.32). Heterogeneity was low and not statistically significant. Publication bias was absent, and quality of papers was high. At meta-regression, no correlation was found between the effect and number of patients in each study, age of patients, basal blood glucose levels. No study formally compared IN versus IM/SC in unconscious patients. This meta-analysis indicates that in conscious T1DM patients IN glucagon and IM/SC glucagon are equally effective in resolution of hypoglycemia.

Survey on hypoglycemia among insulin-treated patients with diabetes: The Colombian International Operations Hypoglycemia Assessment Tool population

Introduction:The non-interventional International Operations Hypoglycemia Assessment Tool (IO-HAT) study assessed the incidence of hypoglycemia in patients with insulin-treated diabetes across nine countries, including a cohort of patients in Colombia.Materials and methods:Hypoglycemia incidence among patients with insulin-treated diabetes was assessed across 26 sites in Colombia. Hypoglycaemic events (any, nocturnal or severe) were reported in self-assessment questionnaires (SAQ) and patient diaries based on capillary blood glucose measurement or symptoms. Retrospective events (severe events 6 months before baseline and any event 4 weeks before baseline) were recorded in SAQ, Part 1, and prospective events (4 weeks from baseline) were recorded in SAQ, Part 2, and patient diaries. Differences in hypoglycemia incidence reported in the retrospective and prospective periods were assessed using two-sided tests.Results:Of the 664 patients assessed, 213 had type 1 diabetes (T1D) and 451 had type 2 diabetes (T2D). Nearly all patients experienced at least one hypoglycaemic event in the prospective period (97.1% T1D; 93.3% T2D). Rates of hypoglycemia (events per person- year, PPY) were higher prospectively than retrospectively for any hypoglycemia (T1 D: 121.6 vs. 83.2, p<0.001; T2D: 28.1 vs. 24.6, p=0.127) and severe hypoglycemia (T 1D: 15.3 vs. 9.2, p=0.605; T 2 D: 9.5 vs. 3.5 p=0.040).Conclusion: These results, the first from a patient-reported dataset on hypoglycemia in insulin-treated patients with diabetes in Colombia, show that patients reported higher rates of any hypoglycemia during the prospective period.

Therapeutic Use of Intranasal Glucagon: Resolution of Hypoglycemia.

Episodes of hypoglycemia are frequent in patients with diabetes treated with insulin or sulphonylureas. Hypoglycemia can lead to severe acute complications, and, as such, both prevention and treatment of hypoglycemia are important for the well-being of patients with diabetes. The experience of hypoglycemia also leads to fear of hypoglycemia, that in turn can limit optimal glycemic control in patients, especially with type 1 diabetes. Treatment of hypoglycemia is still based on administration of carbohydrates (oral or parenteral according to the level of consciousness) or of glucagon (intramuscular or subcutaneous injection). In 1983, it was shown for the first time that intranasal (IN) glucagon drops (with sodium glycocholate as a promoter) increase blood glucose levels in healthy volunteers. During the following decade, several authors showed the efficacy of IN glucagon (drops, powders, and sprays) to resolve hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. Only in 2010, based on evaluation of patients’ beliefs and patients’ expectations, a canadian pharmaceutical company (Locemia Solutions, Montreal, Canada) reinitiated efforts to develop glucagon for IN administration. The project has been continued by Eli Lilly, that is seeking to obtain registration in order to make IN glucagon available to insulin users (children and adolescents) worldwide. IN glucagon is as effective as injectable glucagon, and devoid of most of the technical difficulties associated with administration of injectable glucagon. IN glucagon appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both children and adults.

Self-Reported Hypoglycemia in Insulin-Treated Patients with Diabetes: Results from the Philippine Cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) Study.

ObjectiveTo determine the frequency of hypoglycemia in insulin-treated patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study.MethodologyThis sub-analysis included Filipino patients with T1DM or T2DM, aged 18 years and older, treated with insulin for more than 12 months, who completed the two-part self-assessment questionnaires (SAQ1 and SAQ2) and patient diaries that recorded hypoglycemia during retrospective (6 months/4 weeks before baseline) and prospective period (4 weeks after baseline) (ClinicalTrials.gov number: NCT02306681).ResultsA total of 671 patients were enrolled and completed the SAQ1 (62 patients with T1DM and 609 patients with T2DM). Almost all patients (100% in T1DM and 99.3% in T2DM) experienced at least 1 hypoglycemic event prospectively. The incidence of any hypoglycemia was also high in the prospective period compared to retrospective period (72.6 [95% CI: 64.8, 80.9] events PPY and 43.6 [95% CI: 37.8, 49.9] events PPY; p=0.001, respectively) in T1DM patients.ConclusionAmong insulin-treated patients, higher rates of hypoglycemia were reported prospectively than retrospectively. This indicates that the patients in real-life setting often under-report hypoglycemia. Patient education can help in accurate reporting and appropriate management of hypoglycemia and diabetes.

Self-reported hypoglycemia in insulin-treated patients with diabetes: Results from an international survey on 7289 patients from nine countries.

Hypoglycemia constitutes a significant barrier to achieving glycemic control with insulin in both type 1 and type 2 diabetes. Historically, it has been difficult to accurately verify the rates of hypoglycemia within a clinical setting and there is a need for high-quality, real-world data to ascertain the true rates of hypoglycemia in clinical practice. The global Hypoglycemia Assessment Tool (HAT) study was designed to assess the global incidence of hypoglycemia in patients with insulin-treated diabetes, and the results have indicated that the overall incidence of hypoglycemia is high, with large variations between geographical regions. The International Operations HAT (IO HAT) study retrospectively and prospectively assessed the incidence of hypoglycemia in patients with insulin-treated diabetes in Bangladesh, Colombia, Egypt, Indonesia, Philippines, Singapore, South Africa, Turkey, and United Arab Emirates. During the prospective period, hypoglycemic events were reported by 97.4% of patients with type 1 diabetes and 95.3% of those with type 2 diabetes, with an estimated rate of 6.86 events per patient per month (PPPM) for patients with type 1 diabetes and 2.37 events PPPM for patients with type 2 diabetes. These results represent the first patient-reported dataset on hypoglycemia in the participating countries and confirm that hypoglycemia is under-reported and more widespread than previously believed. Although the incidence of hypoglycemia was variable among patients on different treatment regimens, there were substantial impacts on both productivity and healthcare utilization following an episode of hypoglycemia. This trial is registered at clinicaltrials.gov: NCT02306681.

Risk Factors for Nocturnal Hypoglycemia in Insulin-treated Patients With Type 2 Diabetes: A Secondary Analysis of Observational Data Derived From an Integrated Clinical Trial Database

PurposeA trade-off exists in most diabetes therapies between the benefits of good glycemic control and the morbidity of hypoglycemia. Balancing these factors to achieve desired outcomes is a key consideration for personalized diabetes therapy. Hypoglycemia at night (nocturnal hypoglycemia [NH]) is a common but often under-reported problem in insulin-treated patients with type 2 diabetes. To better understand the risk for NH, we pooled data from multiple clinical trials of insulin treatment and specifically examined NH risk factors in relation to glycemic goals. MethodsOf 53 randomized trials involving insulin treatment, 18 trials that collected NH data were included. Risk factors associated with NH were identified by using gradient-boosting methods. A proportional hazards model was used to quantify the hazard ratio (HR) for risk factors. By modeling with individual patient data, a patient-level NH risk score distribution was created. Finally, results of the model were used to quantify an adjustment to the glycemic goal that would fully offset each risk factor, all other factors being equal. FindingsData pooling resulted in the inclusion of 7341 patients with type 2 diabetes from 18 randomized clinical trials. In the mean 6-month treatment period, 43% of patients experienced at least 1 episode of NH (mean [SD], 1.1 [1.5] events/month). Reduction of glycosylated hemoglobin (HbA1c) levels during the trial was a risk factor for NH (HR, 1.40 [95% CI, 1.38-1.43] per –1% of HbA1c). Higher baseline HbA1c level was a protective factor against NH (HR, 0.76 [95% CI, 0.74–0.77] per +1% of HbA1c); and the adjustment to HbA1c goal required to offset 1% higher baseline HbA1c was –0.825%. Patient characteristics for risk of NH included older age (HR, 1.02 [95% CI, 1.01–1.02]) per 1-year increase), female sex (HR, 1.18 [95% CI, 1.15–1.22]), black or African-American race (HR, 1.41 [95% CI, 1.33–1.50] vs white race), longer diabetes duration (HR, 1.02 [95% CI, 1.01–1.02] per 1-year increase), diabetic nephropathy (HR, 1.40 [95% CI, 1.27–1.54]), and concomitant sulfonylurea use (HR, 1.10 [95% CI, 1.05–1.15]). Asian race was associated with a lower risk of NH (HR, 0.50 [95% CI, 0.48–0.53] vs white race); this finding could be offset with a 2.03% adjustment to the HbA1c goal. ImplicationsData on NH are scarce. By pooling multiple clinical trials, this study was able to evaluate patient-level data. A quantitative understanding of the trade-off between individual risk factors for NH and glycemic reduction may help clinicians to personalize patients’ glycemic goals, while effectively managing NH risk. Limitations of the study include that patients were selected through inclusion/exclusion criteria and that patient compliance may be better in a trial setting. Validating the findings in the real world will be helpful.

The Canadian Hypoglycemia Assessment Tool Program: Insights Into Rates and Implications of Hypoglycemia From an Observational Study.

The true prevalence of hypoglycemia in insulin-treated patients with diabetes and its impact on patients, employers and healthcare providers is poorly appreciated owing to a paucity of real-world data. The global Hypoglycemia Assessment Tool (HAT) study addressed this issue, and here we report data from the Canadian cohort of patients. This noninterventional, 6-month retrospective and 4-week prospective study enrolled patients aged ≥18 years receiving insulin treatment for >12 months from community endocrinology practices. Data were collected using self-assessment questionnaires and patient diaries. The primary endpoint was the proportion of patients experiencing ≥1 hypoglycemic event during the 4-week prospective observational period. Four hundred ninety-eight patients with type 1 diabetes (n=183) and type 2 diabetes (n=315) were enrolled. The prevalence of hypoglycemia was similar in the retrospective (type 1 diabetes, 92.3%; type 2 diabetes, 63.5%) and prospective (type 1 diabetes, 95.2%; type 2 diabetes, 64.2%) periods. Prospective rates of any, nocturnal and severe hypoglycemia per patient-year (95% confidence interval) were 69.3 (66.4; 72.2), 14.2 (12.9; 15.6) and 1.8 [1.4; 2.4]. Higher rates were reported retrospectively, reaching significance for nocturnal hypoglycemia per patient-year (30.0 [28.1; 32.0] vs. 14.2 [12.9; 15.6]; p<0.001). Hypoglycemia led to increased healthcare utilization and absenteeism and was associated with potentially harmful self-care behaviours (e.g., reduced or skipped insulin doses) and increased blood glucose self-monitoring. Prevalence and incidence of hypoglycemia were high among insulin-treated patients with diabetes in Canada, and some patients took harmful or costly actions when they experienced hypoglycemia. Identifying the insulin-treated patients who are at greatest risk may help to reduce the incidence of hypoglycemia.

Self-reported hypoglycemia in insulin-treated patients with diabetes: Results from an international survey of 7289 patients from 9 countries

Self-reported hypoglycemia in insulin-treated patients with diabetes: Results from an international survey of 7289 patients from 9 countries

Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah.

AIMTo measure the incidence and determinants (predictors) of hypoglycemia among patients with type 2 diabetes mellitus (T2DM) who were on insulin treatment for at least one year.METHODSThe present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo (from 15th of April, 2013 to 15th of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.RESULTSThe incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mild hypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.CONCLUSIONHypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.

Continuous glucose monitoring in insulin-treated patients in non-ICU settings.

Inpatient hyperglycemia, in patients with and without a history of diabetes, is associated with increased risk of complications, mortality, and longer hospital stay in medicine and surgical patients. Bedside capillary point of care testing is widely recommended as the preferred method for glucose monitoring and for guiding glycemic management of individual patients; however, the accuracy of most handheld glucose meters is far from optimal. Recent studies in the hospital setting have reported that the use of continuous glucose monitoring (CGM) can provide real-time information about glucose concentration, direction, and rate of change over a period of several days. Because it provides glucose values every 5-10 minutes 24 hours a day, CGM may have an advantage over point of care testing with respect to reducing the incidence of severe hypoglycemia in acute care. Real-time CGM technology may facilitate glycemic control and to reduce hypoglycemia in insulin-treated patients. Recent guidelines, however, have recommended deferring the use of CGM in the adult hospital setting until further data on accuracy and safety become available. In this study, we review the advantages and disadvantages of the use of real-time CGM in the management of dysglycemia in the hospital setting.

Medical resource use, disturbance of daily life and burden of hypoglycemia in insulin-treated patients with diabetes: results from a European online survey

Hypoglycemia is common in patients with diabetes, and any severe hypoglycemic event can increase the fear of future hypoglycemic events. To try to reduce hypoglycemic events, many patients with diabetes maintain their blood glucose levels with a ‘safety margin’ (i.e., at higher than recommended values) and maintain hyperglycemia. Following this strategy leads to raised glycated hemoglobin levels, which are, consequently, linked to an increased risk of diabetic complications and increased healthcare costs. In the present survey (n = 1848), conducted in Germany, France and the UK, approximately a third of the patients were very worried about hypoglycemia, and a similar proportion reported maintaining hyperglycemia. Overall, the mean number of emergency room visits and hospitalizations (excluding emergency room visits) per patient per 12 months was 0.65 and 0.47, respectively. In addition, 10% of the patients reported that they had taken days off work because of hypoglycemia during the previous 12 months. Furthermore, 80% of diabetics in the three countries said they would value a meter that tells them when their blood glucose level is getting high/low at a particular time of the day. Thus, the survey outlines the potential scale, in a real-world setting, of ‘hidden’ costs associated with hypoglycemia and fear of hypoglycemia; such costs are likely to have a major detrimental impact on the overall emotional and economic burden of diabetes, which may be reduced through broader use of blood-glucose monitors for self-monitoring of blood glucose.

Rate of Hypoglycemia in Insulin-Treated Patients with Type 2 Diabetes Can Be Predicted from Glycemic Variability Data

We set out to study the relationship between different measures of glycemic variability and the rate of hypoglycemia in patients with type 2 diabetes. Data were pooled from three 24-week insulin trials including patients on twice-daily (BID) insulin lispro mix 75/25 (75% insulin lispro protamine suspension, 25% insulin lispro) (n=805), daily (QD) insulin glargine (n=1,019), insulin lispro protamine suspension (n=353) (QD or BID), and insulin detemir (n=166) (QD or BID), all with continuation of prestudy oral antihyperglycemic medications. Glycemic variability measures were derived from seven-point self-monitored blood glucose profiles. At baseline, mean (±SD) age was 56.9±9.7 years, duration of type 2 diabetes was 9.5±6.1 years, hemoglobin A1c (HbA1c) was 8.9±1.1%, and 51.9% were male. Intra-day glucose coefficient of variation (CV), fasting blood glucose, intra-day minimum glucose and inter-day glucose CV at 24 weeks, and intra-day glucose CV at baseline were significantly correlated with the rate of hypoglycemia events between Weeks 12 to 24 (P<0.05 for all measures). Intra-day and inter-day glycemic variability is significantly associated with the risk of hypoglycemia in insulin-treated patients with type 2 diabetes, even after adjusting for mean glucose and HbA1c. The intra-day glycemic variability before starting insulin is significantly associated with the risk of hypoglycemia during insulin treatment, which points at treatment- and patient-related factors mediating this relationship.

PREDICTIVE™– a global, prospective observational study to evaluate insulin detemir treatment in types 1 and 2 diabetes: baseline characteristics and predictors of hypoglycaemia from the European cohort

PREDICTIVEtrade mark (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, observational study assessing the safety and efficacy of insulin detemir. We report the study design, population characteristics and baseline observations, including cross-sectional analysis, from 19 911 patients with type 1 or 2 diabetes. Patients with type 1 or 2 diabetes requiring basal insulin are prescribed insulin detemir and followed up for 12-52 weeks. Data on demographics, haemoglobin A(1c) (HbA(1c)), fasting glucose, within-subject fasting glucose variability and weight are collected from patient records (and/or recall for hypoglycaemia). A negative binomial distribution model is used to assess the influence of predictive/confounding variables on hypoglycaemic episodes in insulin-treated patients at baseline. Multi-factorial analysis of covariance is used to evaluate the association of the variables with current body weight and within-subject fasting glucose variability. Total hypoglycaemic episodes in the 4 weeks prior to study start were 47.5 per patient-year in patients with type 1 and 9.2 per patient-year in patients with type 2 diabetes. The frequency of hypoglycaemia in insulin-treated patients showed a significant, positive association with duration of diabetes, number of insulin injections and fasting glucose variability but was inversely related to HbA(1c), fasting glucose and body mass index. Weight showed a significant positive association with gender (male > female) and insulin dosage. Weight was also positively associated with fasting glucose variability in patients with type 1 diabetes, and age and number of injections in patients with type 2 diabetes. These baseline data showed that, in addition to the established relationship with intensive treatment and HbA(1c), frequency of hypoglycaemia was positively associated with fasting glucose variability. Follow-up data from PREDICTIVE will provide insights on insulin detemir in diabetes management.