Impact of a Hypoglycemia Reduction Bundle and a Systems Approach to Inpatient Glycemic Management

Objective: Uncontrolled hyperglycemia and iatrogenic hypoglycemia represent common and frequently preventable quality and safety issues. We sought to demonstrate the effectiveness of a hypoglycemia reduction bundle, proactive surveillance of glycemic outliers, and an interdisciplinary data-driven approach to glycemic management.Methods: Population: all hospitalized adult non–intensive care unit (non-ICU) patients with hyperglycemia and/or a diagnosis of diabetes admitted to our 550-bed academic center across 5 calendar years (CYs). Interventions: hypoglycemia reduction bundle targeting most common remediable contributors to iatrogenic hypoglycemia; clinical decision support in standardized order sets and glucose management pages; measure-vention (daily measurement of glycemic outliers with concurrent intervention by the inpatient diabetes team); educational programs. Measures and analysis: Pearson chi-square value with relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare glycemic control, hypoglycemia, and hypoglycemia management parameters across the baseline time period (TP1, CY 2009–2010), transitional (TP2, CY 2011–2012), and mature postintervention phase (TP3, CY 2013). Hypoglycemia defined as blood glucose <70 mg/dL, severe hypoglycemia as <40 mg/dL, and severe hyperglycemia >299 mg/dL.Results: A total of 22,990 non-ICU patients, representing 94,900 patient-days of observation were included over the 5-year study. The RR TP3:TP1 for glycemic excursions was reduced significantly: hypoglycemic stay, 0.71 (95% CI, 0.65 to 0.79); severe hypoglycemic stay, 0.44 (95% CI, 0.34 to 0.58); recurrent hypoglycemic day during stay, 0.78 (95% CI, 0.64 to 0.94); severe hypoglycemic day, 0.48 (95% CI, 0.37 to 0.62); severe hyperglycemic day (>299 mg/dL), 0.76 (95% CI, 0.73 to 0.80).Conclusion: Hyperglycemia and hypoglycemia event rates were both improved, with the most marked effect on severe hypoglycemic events. Most of these interventions should be portable to other hospitals.Abbreviations: BG = blood glucose CDS = clinical decision support CI = confidence interval CY = calendar year DIG = diabetes initiative group EHR = electronic health record ICU = intensive care unit RR = relative risk SHM = Society of Hospital Medicine TP = time period     

Answering the Challenge: Prevention of Inpatient Hypoglycemia

Abbreviations:BG = blood glucoseEMR = electronic medical record     

Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients

The objective of this study was to explore predictors, including social factors, lifestyle factors, and factors relevant to glycemic control and treatment, for mild and severe hypoglycemia in insulin-treated Japanese diabetic patients. This study included 123 insulin-treated diabetic patients who were referred to the diabetes clinic between January and July 2013 at Shiga University of Medical Science Hospital. After a survey examining the various factors, patients were followed for 6 months. During the follow-up period, blood glucose was self-monitored. Mild hypoglycemia was defined as blood glucose level 50–69 mg/dl, and severe hypoglycemia was defined as blood glucose level ≤49 mg/dl. Multinomial logistic regression was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of each factor for mild and severe hypoglycemia. During the 6-month follow-up period, 41 (33.3%) patients experienced mild hypoglycemia, and 20 (16.3%) experienced severe hypoglycemia. In multivariable-adjusted analyses, assistance from family members at the time of the insulin injection [presence/absence, OR (95% CI): 0.39 (0.16–0.97)] and drinking [current drinker/non- and ex-drinker, OR (95% CI): 4.89 (1.68–14.25)] affected mild hypoglycemia. Assistance from family members at the time of insulin injection [presence/absence, OR (95% CI): 0.19 (0.05–0.75)] and intensive insulin therapy [yes/no, OR (95% CI): 3.61 (1.06–12.26)] affected severe hypoglycemia. In conclusion, our findings suggest that not only a factor relevant to glycemic control and treatment (intensive insulin therapy) but also a social factor (assistance from family members) and a lifestyle factor (current drinking) were predictors for mild or severe hypoglycemia in Japanese insulin-treated diabetic patients.     

马齿苋多糖抗糖尿病作用的实验研究

为了观察马齿苋多糖的抗糖尿病作用,本实验用四氧嘧啶诱导糖尿病模型小鼠,观察了马齿苋多糖液灌胃后5、10和15 d的空腹血糖浓度的改变,以及糖负荷30、60、120 min后葡萄糖耐量变化.结果表明,马齿苋多糖可显著降低糖尿病模型小鼠的血糖和改善其糖耐量异常,且与处理浓度和时间呈正相关性.上述指标显示马齿苋多糖具有抗糖尿病作用.     

Hypoglycemia: Minimizing Its Impact in Type 2 Diabetes

ObjectiveTo review and discuss the risks and impact of hypoglycemia and provide guidance for the prevention of hypoglycemia in type 2 diabetes (T2DM).MethodsWe review and discuss the risks and impact of hypoglycemia, providing specific guidance regarding the prevention of hypoglycemia and judicial selection of glucose-lowering agents in individuals with T2DM.ResultsHypoglycemia in T2DM is underrecognized and underreported. Emerging evidence from large clinical trials suggest that hypoglycemia may be an important risk factor for morbidity and mortality in T2DM. In addition, hypoglycemia is associated with reduced quality of life, greater healthcare utilization costs, and poor adherence to medical regiments.ConclusionThese findings have led professional organizations to emphasize the prevention of hypoglycemia as an important consideration when initiating or intensifying treatment regimens. In clinical settings, particular attention should be paid to a patient’s risk for hypoglycemia when initiating or intensifying the pharmacological treatment regimen. The endocrinologist can play an important role in educating not only the patient, but also other members of the diabetes-management team regarding the need for individualized therapy. (Endocr Pract. 2013;19:526-535)     

Economic Burden of Hypoglycemia in Patients with Type 2 Diabetes Mellitus from Korea

Background

Hypoglycemia is a very serious complication in patients with type 2 diabetes mellitus (T2DM) and affects the economic burden of treatment. This study aims to create models of the cost of treating hypoglycemia in patients with T2DM based upon physician estimates of medical resource usage.

Methods

Using a literature review and personal advice from endocrinologists and emergency physicians, we developed several models for managing patients with hypoglycemia. The final model was approved by the consulting experts. We also developed 3 unique surveys to allow endocrinologists, emergency room (ER) physicians, and primary care physicians to evaluate the resource usage of patients with hypoglycemia. Medical costs were calculated by multiplying the estimated medical resource usage by the corresponding health insurance medical care costs reported in 2014.

Results

In total, 40 endocrinologists, 20 ER physicians, and 30 primary care physicians completed the survey. We identified 12 types of standard medical models for secondary or tertiary hospitals and 4 for primary care clinics based on the use of ER, general ward, or intensive care unit (ICU) and patients’ status of consciousness and self-respiration. Estimated medical costs per person per hypoglycemic event ranged from $17.28 to $1,857.09 for secondary and tertiary hospitals. These costs were higher for patients who were unconscious and for those requiring ICU admission.

Conclusion

Hypoglycemia has a substantial impact on the medical costs and its prevention will result in economic benefits for T2DM patients and society.     

Severe Hypoglycemia in a Juvenile Diabetic Rat Model: Presence and Severity of Seizures Are Associated with Mortality

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14–16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4±1.3 mM) than in CON rodents (6.3±0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8±0.2 mM) and CON animals (1.6±0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.     

Simulating the Impact of Improved Cardiovascular Risk Interventions on Clinical and Economic Outcomes in Russia

Objectives

Russia faces a high burden of cardiovascular disease. Prevalence of all cardiovascular risk factors, especially hypertension, is high. Elevated blood pressure is generally poorly controlled and medication usage is suboptimal. With a disease-model simulation, we forecast how various treatment programs aimed at increasing blood pressure control would affect cardiovascular outcomes. In addition, we investigated what additional benefit adding lipid control and smoking cessation to blood pressure control would generate in terms of reduced cardiovascular events. Finally, we estimated the direct health care costs saved by treating fewer cardiovascular events.

Methods

The Archimedes Model, a detailed computer model of human physiology, disease progression, and health care delivery was adapted to the Russian setting. Intervention scenarios of achieving systolic blood pressure control rates (defined as systolic blood pressure <140 mmHg) of 40% and 60% were simulated by modifying adherence rates of an antihypertensive medication combination and compared with current care (23.9% blood pressure control rate). Outcomes of major adverse cardiovascular events; cerebrovascular event (stroke), myocardial infarction, and cardiovascular death over a 10-year time horizon were reported. Direct health care costs of strokes and myocardial infarctions were derived from official Russian statistics and tariff lists.

Results

To achieve systolic blood pressure control rates of 40% and 60%, adherence rates to the antihypertensive treatment program were 29.4% and 65.9%. Cardiovascular death relative risk reductions were 13.2%, and 29.6%, respectively. For the current estimated 43,855,000-person Russian hypertensive population, each control-rate scenario resulted in an absolute reduction of 1.0 million and 2.4 million cardiovascular deaths, and a reduction of 1.2 million and 2.7 million stroke/myocardial infarction diagnoses, respectively. Averted direct costs from current care levels ($7.6 billion [in United States dollars]) were $1.1 billion and $2.6 billion, respectively.     

Clinical Presentation and Diagnostic Approach to Hypoglycemia in Adults Without Diabetes Mellitus

ObjectiveTo review the clinical presentation, causes, and diagnostic approach to spontaneous hypoglycemia in adults without diabetes mellitus.MethodsA literature review was performed using the PubMed and Google Scholar databases.ResultsHypoglycemia is uncommon in people who are not on glucose-lowering medications. Under normal physiologic conditions, multiple neural and hormonal counterregulatory mechanisms prevent the development of abnormally low levels of plasma glucose. If spontaneous hypoglycemia is suspected, the Whipple triad should be used to confirm hypoglycemia before pursuing further diagnostic workup. The Whipple criteria include the following: (1) low levels of plasma glucose, (2) signs or symptoms that would be expected with low levels of plasma glucose, and (3) improvement in those signs or symptoms when the level of plasma glucose increases. Spontaneous hypoglycemia can be caused by conditions that cause endogenous hyperinsulinism, including insulinoma, postbariatric hypoglycemia, and noninsulinoma pancreatogenous hypoglycemia. Spontaneous hypoglycemia can also be seen with critical illness, hepatic or renal dysfunction, hormonal deficiency, non–diabetes-related medications, and non–islet cell tumors. The initial diagnostic approach should begin by obtaining a detailed history of the nature and timing of the patient’s symptoms, medications, underlying comorbid conditions, and any acute illness. A laboratory evaluation should be conducted at the time of the spontaneous symptomatic episode. Supervised tests such as a 72-hour fast or mixed-meal test may be needed to recreate the situation under which the patient is likely to experience symptoms.ConclusionWe provide an overview of the physiology of counterregulatory response to hypoglycemia, its causes, and diagnostic approaches to spontaneous hypoglycemia in adults.     

Evaluating the Impact of Inadequate Meal Consumption on Insulin-Related Hypoglycemia in Hospitalized Patients

ObjectiveMeal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia. The frequency of reduced meal intake in hospitalized patients remains inadequately determined. This quality improvement project evaluates the percentage of meals consumed by hospitalized patients with insulin orders and the resulting risk of postmeal hypoglycemia (blood glucose [BG] <70 mg/dL, <3.9 mmol/L).MethodsThis was a retrospective quality improvement project evaluating patients with any subcutaneous insulin orders hospitalized at a regional academic medical center between 2015 and 2017. BG, laboratory values, point of care, insulin administration, diet orders, and percentage of meal consumed documented by registered nurses were abstracted from electronic health records.ResultsMeal consumption ≥50% was observed for 85% of meals with insulin orders, and bedside registered nurses were accurate at estimating this percentage. Age ≥65 years was a risk factor for reduced meal consumption (21% of meals 0%-49% consumed, P < .05 vs age < 65 years [12%]). Receiving meal-time insulin and then consuming only 0% to 49% of a meal (defined here as a mismatch) was not rare (6% of meals) and increased postmeal hypoglycemia risk. However, the attributable risk of postmeal hypoglycemia due to this mismatch was low (4 events per 1000) in patients with premeal BG between 70 and 180 mg/dL.ConclusionThis project demonstrates that hospitalized patients treated with subcutaneous insulin have a low attributable risk of postmeal hypoglycemia related to inadequate meal intake.     

Economic Burden of Heart Failure: Investigating Outpatient and Inpatient Costs in Abeokuta,Southwest Nigeria

Background: Heart failure (HF) is a deadly, disabling and often costly syndrome world-wide. Unfortunately, there is a paucity of data describing its economic impact in sub Saharan Africa; a region in which the number of relatively younger cases will inevitably rise. Methods: Heath economic data were extracted from a prospective HF registry in a tertiary hospital situated in Abeokuta, southwest Nigeria. Outpatient and inpatient costs were computed from a representative cohort of 239 HF cases including personnel, diagnostic and treatment resources used for their management over a 12-month period. Indirect costs were also calculated. The annual cost per person was then calculated. Results: Mean age of the cohort was 58.0±15.1 years and 53.1% were men. The total computed cost of care of HF in Abeokuta was 76, 288,845 Nigerian Naira (US$508, 595) translating to 319,200 Naira (US$2,128 US Dollars) per patient per year. The total cost of in-patient care (46% of total health care expenditure) was estimated as 34,996,477 Naira (about 301,230 US dollars). This comprised of 17,899,977 Naira- 50.9% ($US114,600) and 17,806,500 naira −49.1%($US118,710) for direct and in-direct costs respectively. Out-patient cost was estimated as 41,292,368 Naira ($US 275,282). The relatively high cost of outpatient care was largely due to cost of transportation for monthly follow up visits. Payments were mostly made through out-of-pocket spending. Conclusion: The economic burden of HF in Nigeria is particularly high considering, the relatively young age of affected cases, a minimum wage of 18,000 Naira ($US120) per month and considerable component of out-of-pocket spending for those affected. Health reforms designed to mitigate the individual to societal burden imposed by the syndrome are required.     

糖尿病酮症酸中毒21例救治探讨

目的:探讨糖尿病酮症酸中毒(diabetic ketoacidosis,DKA)抢救过程中的经验和体会.方法:对21例DKA患者的临床资料进行分析,21例酮症酸中毒患者经积极抢救治疗,在补液、祛除诱因及纠正电解质紊乱、酸碱平衡等治疗的基础上均给予小剂量普通胰岛素静脉滴注;治疗时小心处理液体和电解质的紊乱,严密监护有关并发症的临床和生化参数,包括低血钾,低血糖、脑水肿等,及时调整胰岛素的静脉输入量.随着酸中毒的的改善病情稳定后,胰岛素的静脉输入改为三餐前皮下注射,控制血糖浓度在8.3～13.9 mmol·L-1.结果:经综合治疗后,21例患者各项指标在3天内恢复至正常范围,治疗取得了良好的效果.结论:DKA的救治是个综合的过程,适时、合理的补液和使用胰岛素、抗感染、纠正酸中毒及电解质平衡紊乱对提高DKA的救治成功率具有重要的临床意义.     

Clinical Manifestations and Current Treatment options for Diabetic Neuropathies

ObjectiveTo review the clinical manifestations and current treatment options for diabetic neuropathies, one of the most common complications of diabetes mellitus.MethodsWe performed a MEDLINE search of the English-language literature using a combination of words (diabetic neuropathy, diabetic autonomic neuropathy, diagnosis and treatment) to identify original studies, consensus statements, and reviews on diabetic neuropathies published in the past 25 years. Emphasis was placed on clinical manifestations of distal polyneuropathy and its treatment, especially new therapies.ResultsDistal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve fiber neuropathy often presents with pain and loss of intraepidermal nerve fibers, but without objective signs or electrophysiologic evidence of nerve damage. This type of neuropathy is a component of impaired glucose tolerance and the metabolic syndrome. The greatest risk from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve fiber neuropathy produces numbness, ataxia, and incoordination, thus impairing activities of daily living and causing falls and fractures. Successfully treating diabetic neuropathy requires addressing the underlying pathogenic mechanisms, treating symptoms to improve quality of life, and preventing progression and complications of diabetes mellitus. Two new drugs, duloxetine hydrochloride and pregabalin, have recently been approved for treatment of neuropathic pain associated with diabetes mellitus.ConclusionSymptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for clinically significant reduction of morbidity and mortality. Preventive strategies and patient and physician education still remain key factors in reducing complication rates and mortality. (Endocr Pract. 2007;13:550-566)     

The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis

Background

Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique.

Methods and Findings

We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%–61.0%), increasing to 65.0% (95% CI, 64.9%–65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6–9.6 y) and US$2,440 (95% CI, US$2,440–US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3–10.3 y) and US$2,800 (95% CI, US$2,790–US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480–US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4.

Conclusions

POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors'' Summary     

胰岛素持续皮下输注对2型糖尿病微血管病变影响的研究

目的:观察持续皮下胰岛素输注(CSⅡ)对2型糖尿病(T2DM)微血管病变的影响.方法:80例T2DM微血管病变患者应用4周CSⅡ强化治疗,比较治疗前后患者血清炎症因子:C-反应蛋白(CRP)、高敏C-反应蛋白(hSCRP);血清Ⅳ型胶原(CⅣ);纤溶因子:组织型纤溶酶原激活剂(t-PA)、组织型纤溶酶原激活剂抑制物(PAI-1)浓度的变化.结果:①T2DM微血管病变组患者CRP、hsCRP、CⅣ、PAI-1水平显著高于正常对照组(P＜0.01),t-PA水平显著低于正常对照组(P＜0.01).②CSⅡ治疗4周后空腹血糖、餐后2h血糖显著降低(P＜0.01);糖化血红蛋白、胰岛素抵抗指数、CRP、hsCRP、CⅣ均降低(P＜0.05);PAI-1显著降低(P＜0.0l),t-PA显著升高(P＜0.01).结论:T2DM微血管病变与血清炎症因子;CⅣ;纤溶因子有关,CSⅡ治疗除能降血糖外,还能显著降低血清炎症因子、CⅣ水平,改善纤溶因子功能,减轻胰岛素抵抗.