Lower Risk Of Severe Hypoglycemia Research Articles

Effects of real-time continuous glucose monitoring in type 1 diabetes: a meta-analysis of randomized controlled trials.

Self-monitoring of blood glucose (SMBG) represented a major breakthrough in the treatment of type 1 diabetes. The aim of the present meta-analysis is to assess the effect of continues glucose monitoring (CGM) and flash glucose monitoring (FGM), on glycemic control in type 1 diabetes. The present analysis includes randomized clinical trials comparing CGM or FGM with SMBG, with a duration of at least 12weeks, identified in Medline or clinicaltrials.gov. The principal endpoint was HbA1c at the end of the trial. A secondary endpoint was severe hypoglycemia. Mean and 95% confidence intervals for HbA1c and Mantel-Haenzel odds ratio [MH-OR] for severe hypoglycemia were calculated, using random effect models. A sensitivity analysis was performed using fixed effect models. In addition, the following secondary endpoints were explored, using the same methods: time in range, health-related quality of life, and treatment satisfaction. Separate analyses were performed for trials comparing CGM with SMBG, and those comparing CGM + CSII and SMBG + MDI and CGM-regulated insulin infusion system (CRIS) and CSII + SMBG. CGM was associated with a significantly lower HbA1c at endpoint in comparison with SMBG (- 0.24 [- 0.34, - 0.13]%); CGM was associated with a significantly lower risk of severe hypoglycemia than SMBG. Treatment satisfaction and quality of life were not measured, or not reported, in the majority of studies. FGM showed a significant reduction in the incidence of mild hypoglycemia and an increased treatment satisfaction, but no significant results are shown in HbA1c. CGM + CSII in comparison with SMBG + MDI was associated with a significant reduction in HbA1c. Only two trials with a duration of at least 12weeks compared a CRIS with SMBG + CSII; HbA1c between the two treatment arms was not statistically significant (difference in means: - 0.23 [- 0.91; 0.46]%; p = 0.52). GCM compared to SMBG has showed a reduction in HbA1c and severe hypoglycemia in patient with type 1 diabetes. The comparison between CGM + CSII and SMBG + MDI showed a large reduction in HbA1c; it is conceivable that the effects of CSII + CGM on glycemic control additives. The only comparison available between FGM and SMBG was conducted in patients in good control.

1619-P: Trends in Severe Hypoglycemia and Mortality in Individuals with Type 1 Diabetes

Background: Hypoglycemia is one of the major complications in the management of individuals with type 1 diabetes, and severe hypoglycemia increases the risk of mortality. Objective: To investigate trends and risk factors for severe hypoglycemia and mortality in individuals with type 1 diabetes. Methods: We evaluated age- and sex-standardized annual incidence rates of severe hypoglycemia requiring hospitalization and mortality in individuals with type 1 diabetes using the Korean National Health Insurance Service Database from 2002 to 2016. Results: Age- and sex-standardized incidence rates of severe hypoglycemia have increased from 2002 to 2016 in individuals with type 1 diabetes (5.79 per 1,000 in 2002-2004 to 12.57 per 1,000 in 2015-2016, P for trend < 0.0001). Individuals with severe hypoglycemia had significantly lower body weight (64.8 ± 12.4 kg vs. 57.7 ± 9.5 kg; P < 0.0001) and higher proportions of chronic kidney disease (2.5% vs. 5.3%, P = 0.0012) and end-stage renal disease (0.6% vs. 2.0%, P = 0.0071) compared with those without severe hypoglycemia. However, age- and sex-standardized mortality has decreased in both individuals with and without severe hypoglycemia (P for trends < 0.001). The use of new-generation insulin analogs was associated with a lower risk of severe hypoglycemia and mortality. Conclusion: The incidence rates of severe hypoglycemia have significantly increased, while the mortality has significantly decreased in Korean individuals with type 1 diabetes from 2002 to 2016. Disclosure J. Bae: None. K. Kim: None. J. Kim: None. S. Kim: None. N. Kim: None.

Cardiovascular (CV) Safety and Severe Hypoglycemia Benefit of Insulin Degludec vs. Insulin Glargine U100 in Older Patients (=65 Years) with Type 2 Diabetes (T2D)—Observations from DEVOTE

There is limited comparative evidence for the CV safety and hypoglycemia risk of basal insulins in older patients with T2D. This secondary analysis from DEVOTE investigated the CV safety and severe hypoglycemia risk of insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100) in older patients (65-74 and ?75 years age groups). Data from DEVOTE (a treat-to-target, randomized, double-blind trial evaluating 7637 patients with T2D over a median period of 2 years at high risk of CV events) were stratified by three age groups. At baseline, A1C, fasting plasma glucose and estimated glomerular filtration rates decreased with increasing age. Older patients had a higher risk of major adverse cardiovascular events (MACE), all-cause mortality and severe hypoglycemia, regardless of treatment. Treatment differences for MACE, all-cause mortality and severe hypoglycemia were similar across age groups (Figure), with no significant interactions between treatment and age group. Degludec was associated with a lower risk of severe hypoglycemia vs. glargine U100, regardless of age. This analysis supported the CV safety of degludec and demonstrated a lower risk of severe hypoglycemia vs. glargine U100 in older patients with T2D. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc. S.S. Emerson: Consultant; Self; Bayer AG, CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals Group, Genentech, Inc., GlaxoSmithKline plc., Janssen Research & Development, Novartis AG, Novo Nordisk A/S, Pfizer Inc., Roche Pharma, Allergan, AstraZeneca, Coherus Biosciences Inc, Emmaus Life Sciences Inc., Indivior, Sandoz, Seattle Genetics. Research Support; Self; National Heart, Lung, and Blood Institute. E. Franek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Servier. M.P. Gilbert: Consultant; Self; Sanofi US, Novo Nordisk A/S. S.P. Marso: Consultant; Self; Abbott Vascular, Novo Nordisk A/S, University of Oxford, AstraZeneca, Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk A/S, The Medicines Company, Terumo Medical Corporation. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. C.T. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. M.V. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Mark: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A.C. Moses: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott.

Assessing the Impact of an Order Panel Utilizing Weight-Based Insulin and Standardized Monitoring of Blood Glucose for Patients With Hyperkalemia

Intravenous insulin with glucose is used in urgent treatment for hyperkalemia but has a significant risk of hypoglycemia. The authors developed an order panel within the electronic health record system that utilizes weight-based insulin dosing and standardized blood glucose monitoring to reduce hypoglycemia. As initial evaluation of this protocol, the authors retrospectively compared potassium and blood glucose lowering in patients treated with the weight-based (0.1 units/kg) insulin order panel (n = 195) with those given insulin based on provider judgment (n = 69). Serum potassium lowering did not differ between groups and there was no relationship between dose of insulin and amount of potassium lowering. There was a difference in hypoglycemia rates between groups ( P = .049), with fewer severe hypoglycemic events in the panel (2.56%) than in the non-panel group (10.14%). These data suggest weight-based insulin dosing is equally effective for lowering serum potassium and may lower risk of severe hypoglycemia.

Persistence with rapid-acting insulin and its association with A1C level and severe hypoglycemia among elderly patients with type 2 diabetes

Objective: To examine the persistence with rapid-acting insulin (RAI) and its association with clinical outcomes among elderly patients with type 2 diabetes (T2D).Methods: This observational, retrospective cohort study analyzed RAI persistence and its association with change in glycated hemoglobin A1c and risk of severe hypoglycemia among elderly (≥65 years) Medicare beneficiaries with T2D who added RAI to their basal insulin regimen.Results: Among T2D patients with >1 RAI prescriptions (n = 3927), only 21% were persistent. Baseline factors positively associated with RAI persistence (adjusted odds ratio [95% CI]) were: age ≥75 vs. 65–74 years: 1.20 (1.01–1.43); use of ≥3 oral antidiabetes drugs: 1.63 (1.16–2.28); cognitive impairment: 1.34 (1.03–1.73); and A1C >9.0%: 1.58 (1.15–2.17). Elderly T2D patients having emergency department visits (0.73 [0.59–0.91]) and higher RAI out-of-pocket costs (≥$75 vs. $0 – <$6.40: 0.56 [0.44–0.70]) were less likely to be persistent. Persistent RAI users had a significantly higher reduction in A1C (beta coefficient [standard error]): −0.24 (0.10) and lower odds of severe hypoglycemia (adjusted odds ratio [95% CI]): 0.73 (0.53–0.99).Conclusion: Among elderly T2D patients, persistence with RAI added to basal insulin was associated with improved glycemic control and lower risk of severe hypoglycemia. Despite treatment effectiveness, RAI persistence was poor and might be improved by reducing RAI out-of-pocket costs.

Insulins NPH, glargine, and detemir, and risk of severe hypoglycemia among working-age adults*

Introduction: The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.Methods: All persons aged 18–65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006–2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.Results: A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).Conclusions: Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults.KEY MESSAGESThe comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear.Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin.Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Prevalence of Insulin Pump Therapy and Its Association with Measures of Glycemic Control: Results from the Canadian Study of Longevity in Type 1 Diabetes.

We aimed to determine cross-sectional insulin pump prevalence and factors associated with measures of glycemic control as a secondary analysis in a long-standing type 1 diabetes mellitus (T1DM) national cohort. Canadian participants with ≥50 years of T1DM (n = 305) were administered a comprehensive mail-based questionnaire including acquisition of contemporaneous laboratory results. Factors associated with pump use, glycosylated hemoglobin (HbA1c), and hypoglycemia were analyzed by regression. The 305 participants had a median age of 65 [interquartile range, 59, 71] years, median diabetes duration of 54 [51, 59] years, and mean HbA1c level of 7.5 ± 1.1%. Prevalence of pump use was 44% (133/305), with median duration of use 8 [4, 13] years. Compared with the non-pump subgroup, the pump subgroup had numerically lower but similar HbA1c levels (7.4 ± 0.9% vs. 7.6 ± 1.2%; P = 0.22) and reported greater numbers of minor hypoglycemia events (6.5 vs. 5.1 events/patient·month; P = 0.004) and fewer severe hypoglycemia events (0.5 vs. 1.3 events/patient·year; P = 0.02) in the past year. More frequent daily glucose tests and more frequent minor hypoglycemia events-but not pump therapy or its prescription parameters-were independently associated with lower HbA1c level in multivariable regression. However, use of insulin pump and habitual use of continuous glucose monitoring (≥1 week/month) were each independently associated with lower risk of severe hypoglycemia (risk ratio = 0.50 [P < 0.0001] and 0.30 [P = 0.001], respectively). Insulin pump and continuous glucose monitoring technologies were associated with lower risk of severe hypoglycemia, while frequent daily glucose testing was associated with lower HbA1c level. These findings imply that basic self-management skill and technology play complementary roles in glycemic control among older adults with long-standing T1DM.

Association between hypoglycemia and the type of insulin in diabetic patients treated with multiple injections: an observational study.

Hypoglycemia may have serious health consequences; therefore, it is important to expand knowledge on the factors that increase its prevalence. The aim of the study was to evaluate the effect of the type of insulin-human vs. analogue-on the incidence of mild and severe hypoglycemia, body weight, and hemoglobin A1c (HbA1c) levels. A total of 203 diabetic patients treated with intensive insulin therapy completed the questionnaire on hypoglycemia at baseline and at 3 and 6 months of the follow‑up. Body weight and HbA1c levels were measured at baseline and at 6 months. Incidence of mild and severe hypoglycemia, body weight, and HbA1c levels were compared between patients treated with short‑acting analogue and those treated with short‑acting human insulin (regardless of the type of long‑acting insulin used) and between patients receiving short- and long‑acting analogue insulin and those receiving short- and long‑acting human insulin. A multiple logistic regression analysis was used to find independent risk factors of severe hypoglycemia. At baseline, mild hypoglycemia was more common in patients receiving insulin analogue. There were no differences between the subgroups in the incidence of severe hypoglycemia, HbA1c levels, and body weight. Male sex, older age, and the dose of long‑acting insulin were independently associated with a higher incidence of severe hypoglycemia. Type 2 diabetes and higher body weight were associated with a lower risk of severe hypoglycemia. Our results suggest that use of insulin analogues may predispose to more frequent episodes of mild hypoglycemia, but it does not increase the incidence of severe hypoglycemia in patients on intensive insulin therapy. Insulin analogues are not different from human insulin in terms of the effects on HbA1c levels and body mass.

Glucose Metabolism in Critically Ill Patients

Critical illness afflicts millions of people worldwide and is associated with a high risk of organ failure and death or an adverse outcome with persistent physical or cognitive deficits. Spontaneous hyperglycemia is common in critically ill patients and is associated with an adverse outcome compared to normoglycemia. Insulin is used for treating hyperglycemia in the critically ill patients but may be complicated by hypoglycemia, which is difficult to detect in these patients and which may lead to serious neurological sequelae and death. The incretin hormone, glucagon-like peptide (GLP) 1, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar characteristics and are, among other things, both characterized by different grades of systemic inflammation and insulin resistance. The GLP-1 might be a potential new treatment target in critically ill patients with stress-induced hyperglycemia.

Hypoglycemia in Type 1 Diabetic Pregnancy

OBJECTIVEA recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy.RESEARCH DESIGN AND METHODSIAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model.RESULTSOf the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91–3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38–4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS).CONCLUSIONSThese data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.

Continuous Subcutaneous Insulin Infusion: A New Way to Lower Risk of Severe Hypoglycemia, Improve Metabolic Control, and Enhance Coping in Adolescents with Type 1 Diabetes

Continuous Subcutaneous Insulin Infusion: A New Way to Lower Risk of Severe Hypoglycemia, Improve Metabolic Control, and Enhance Coping in Adolescents with Type 1 Diabetes

Continuous Subcutaneous Insulin Infusion (CSII): A "New" Way to Lower Risk of Severe Hypoglycemia, Improve Metabolic Control, and Enhance Coping in Adolescents with Diabetes

Continuous Subcutaneous Insulin Infusion (CSII): A New Way to Lower Risk of Severe Hypoglycemia, Improve Metabolic Control, and Enhance Coping in Adolescents with Diabetes