Cognitive function during insulin-induced hypoglycemia in humans: Short-term cerebral adaptation does not occur

It has been suggested that cerebral adaptation may occur in response to short-term hypoglycemia. This was examined in the present study by measuring serial changes in cognitive function and symptoms after 60 min of continuous hypoglycemia. Hypoglycemia was induced with a hyperinsulinemic glucose clamp on two separate occasions in 24 non-diabetic human subjects. Cognitive function was assessed using the following cognitive test battery: Paced Auditory Serial Addition Test (PASAT), Rapid Visual Information Processing (RVIP), Trail-Making B (TMB), Digit Symbol Substitution Test (DSST) and Four Choice Reaction Time (CRT). In condition A the blood glucose was maintained at 4.5 mmol/l throughout. On two separate occasions (condition B and condition C) the blood glucose was stabilised at 4.5 mmol/l for 30 min, lowered to 2.5 mmol/l for 60 min and restored to 4.5 mmol/l for 30 min. In each condition the cognitive test battery was performed immediately after stabilisation of blood glucose at 4.5 mmol/l and the subsequent battery was repeated at different time intervals: condition A — after a further 40 min of euglycemia; condition B — after 5 min of hypoglycemia; condition C — after 40 min of hypoglycemia. Acute hypoglycemia induced a significant deterioration in cognitive function which was manifest in all tests except TMB (P<0.05), but performance ability did not differ between conditions B and C. Symptom scores, assessed by a scaled questionnaire, increased significantly during hypoglycemia (P<0.001) but no differences were detected between the scores at 30 min and 60 min. In non-diabetic humans, no improvement appears to occur either in cognitive function or in symptom score after 40–60 min of hypoglycemia (2.5 mmol/l), suggesting that cerebral adaptation does not occur during this period of time.     

老年2型糖尿病患者治疗过程中发生严重低血糖的危险因素

目的考察老年2型糖尿病患者治疗过程中发生严重低血糖的危险因素。方法选择2013年5月-2014年5月收治的发生严重低血糖的糖尿病患者100例并设为观察组,并选取同期收治的未发生严重低血糖的糖尿病患者100例作为对照组,比较两组患者的临床资料,并分析出现严重低血糖的影响因素。结果两组患者的年龄、病程、体重指数（BMI）、血清肌酐（Cr）、尿微量清蛋白（UMA）比较,差异有统计学意义（P〈0.05,P〈0.01）;经Logistic多元回归分析检测,年龄（OR=1.81,P〈0.01）、BMI（OR=0.65,P〈0.05）和UMA（OR=2.39,P〈0.05）是严重低血糖发生的危险因素,其中高BMI是2型糖尿病患者发生严重低血糖的保护性因素,而年龄和UMA则是危险因素。结论2型糖尿病治疗过程中的严重低血糖是多种因素共同作用的结果,减少危险因素并针对性地进行护理有助于降低严重低血糖的发生。     

2型糖尿病合并低血糖实施人性化护理干预对提高患者生存质量的作用

目的：探讨人性化护理对2型糖尿病合并低血糖患者生存质量的影响,并总结经验体会。方法回顾性分析2012年1月~2013年6月期间来我院诊治的146例2型糖尿病合并低血糖患者,将其平均分为观察组和对照组,各73例。对照组实施普通护理,观察组则在普通护理基础上实施人性化护理,比较两组患者的生存质量。结果观察组患者实施人性化护理后,患者的生存质量评分明显高于对照组,且患者的满意度高,差异具有统计学意义（P＜0.05）。结论人性化护理可以显著改善2型糖尿病合并低血糖患者的病情,提高患者的生存质量,值得在临床护理中推广使用。     

老年2型糖尿病血糖波动与夜间低血糖风险的相关性

目的:对行动态血糖监测的老年2型糖尿病患者的资料进行回顾性调查,探讨老年2型糖尿痛患者血糖波动与夜间低血糖风险的相关性.方法:研究对象为2007年1月- 2011年1月行动态血糖监测的337例老年2型糖尿病患者;根据2011年《中国血糖监测临床应用指南》,以MAGE作为血糖波动评估指标,分为正常MAGE组和异常MAGE组.应用SPSS17.0统计软件进行统计学分析.结果:异常MAGE组的低血糖指数(LBGI)、夜间低血糖时间显著高于正常MAGE组(P＜0.01).直线回归分析显示MAGE与LBGI显著相关(r=0.320,P＜0.01).非条件多因素Logistic回归分析显示,在调整性别、年龄、BMI、糖尿病病程和糖化血红蛋白后,MAGE是夜问低血糖风险增加的重要影响因素,其OR( 95％CI)为1.842( 1.084～3.133,P＜ 0.05).结论:老年2型糖尿病血糖波动与夜间低血糖风险增加密切相关.     

加用维格列汀对胰岛素治疗的2型糖尿病患者无症状低血糖发生率的影响

目的观察接受胰岛素治疗的2型糖尿病患者加用二肽基肽酶Ⅳ抑制剂维格列汀后,其低血糖(包括无症状低血糖事件)发生率能否降低。方法将2018年3月至9月于我院内分泌科接受胰岛素治疗的80例2型糖尿病患者随机分为研究组(联用维格列汀共40例)和对照组(不联用二肽基肽酶Ⅳ抑制剂共40例),监测其4周内发生的低血糖事件(包括无症状低血糖),比较两组发生低血糖的例数及事件数,并观察4周后所有患者血糖参数的变化。结果研究组和对照组发生低血糖总人数(18例次对23例次)[包括无症状低血糖的人数(10例次对16例次)]差异无统计学意义(P>0.05);研究组无症状低血糖事件数(14例次对27例次)少于对照组(P<0.05),总低血糖事件数(33例次对52例次)亦少于对照组(P<0.05)。Poisson回归分析显示无感知低血糖事件的发生与糖尿病病程(P<0.01)、空腹血糖(P<0.05)和研究组别(P<0.05)相关。4周后研究组和对照组的糖化血红蛋白、糖化白蛋白、空腹和餐后血糖均改善(P<0.05)。结论在接受胰岛素治疗的2型糖尿病患者中,加用维格列汀在改善其血糖控制同时,亦可降低无症状低血糖事件的发生率并减少总低血糖事件的发生。     

The burden of severe hypoglycemia in type 2 diabetes

Aims: More than 29 million people in the US have type 2 diabetes mellitus (T2DM), a chronic metabolic disorder characterized by a progressive deterioration of glucose control, which eventually requires insulin. Abnormally low levels of blood glucose, a feared side-effect of insulin treatment, may cause severe hypoglycemia (SHO), leading to emergency department (ED) admission, hospitalization, and long-term complications; these, in turn, drive up the costs of T2DM. This study’s objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T2DM using insulin.

Methods: Using Truven MarketScan claims, we identified adult T2DM patients using basal and basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010–2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including ED visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated, and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts.

Results: We identified 66,179 patients using basal and 81,876 patients using basal-bolus insulin, of which ～1.1% (basal) to 3.2% (basal-bolus) experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. those in the inpatient and outpatient SHO groups), 27% (basal) and 40% (basal-bolus) experienced at least one SHO-related hospitalization. One-third of basal and about one-quarter of basal-bolus patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. Inpatient SHO patients using basal insulin stayed in the hospital, including time in the ED, for 2.8 days and incurred $6896 in costs; patients using basal-bolus insulin stayed in the hospital for 2.6 days and incurred costs of $5802. Forty-to-fifty percent of inpatient SHO patients were hospitalized again for SHO. Inpatient SHO patients using basal insulin incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the other two groups ($2935 vs $1819 and $1638), corresponding to 61% and 79% higher monthly costs; patients using basal-bolus insulin also incurred significantly higher monthly costs than patients in the other groups ($3606 vs $2731 and $2607), corresponding to 32% and 38% higher monthly costs.

Limitations: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders.

Conclusions: The burden associated with SHO is not negligible. Nearly one in three patients using only basal insulin and one in four patients using basal-bolus regimens who experienced SHO were hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incurred at least $1,116 (62%) and $875 (70%) more per month than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T2DM.     

实时动态胰岛素泵治疗初发2型糖尿病的疗效观察

目的：观察实时动态胰岛素泵（SAP）与单纯胰岛素泵持续皮下输注胰岛素（CSII）治疗初发2型糖尿病的疗效及安全性。方法随机将40例初发2型糖尿病患者分为两组，每组20例。S A P组用722型胰岛素泵持续皮下输注超短效胰岛素及餐前追加大剂量调整血糖，应用实时动态血糖监测系统（RT -CGMS）监测血糖；单纯CSII组用712型胰岛素泵持续皮下输注超短效胰岛素及餐前追加大剂量调整血糖，应用血糖仪监测指尖血糖。结果两组治疗后空腹血糖（FPG ）、餐后2 h血糖（2hPG）均有显著下降，但两组间差异无统计学意义（P＞0．05）；SAP组与单纯CSII组比较，血糖达标时间（3．7±0．4）VS（4．4±0．5），差异有统计学意义（P＜0．001），低血糖发生频次（0．25±0．44） VS ．（0．60±0．50），差异有统计学意义（P＜0．05）。结论 SAP治疗初发2型糖尿病较CSII更快、更安全，在显著降低血糖的同时并不增加低血糖风险。     

Glucagon: Its evolving role in the management of hypoglycemia

More than 10% of the United States population has diabetes, characterized by hyperglycemia. Insulin and other agents used to treat diabetes predispose people to hypoglycemia, which can be life threatening. Glucagon is an emergency medication that can save lives by quickly raising glucose in people who are unconscious or unable to consume glucose due to severe hypoglycemia. Although glucagon has been commercially available since 1960, earlier formulations required reconstitution of a dry powder with diluent immediately prior to injection, due to lack of long-term stability once reconstituted. Glucagon has been underutilized due to the lack of confidence or ability to administer in emergency situations. More recently, new formulations including a nasal powder glucagon and liquid-stable glucagon have become available. This article discusses the evidence surrounding new glucagon formulations compared with the original glucagon emergency kit including ease of use, efficacy, and safety with a focus on important patient counseling points and relevant clinical information on hypoglycemia.     

The burden of severe hypoglycemia in type 1 diabetes

Aims: Approximately 1.25 million people in the US have type 1 diabetes mellitus (T1DM), a chronic metabolic disease that develops from the body’s inability to produce insulin, and requires life-long insulin therapy. Poor insulin adherence may cause severe hypoglycemia (SHO), leading to hospitalization and long-term complications; these, in turn, drive up costs of SHO and T1DM overall. This study’s objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T1DM using basal-bolus insulin.

Methods: Using Truven MarketScan claims, we identified adult T1DM patients using basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010–2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including emergency department (ED) visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts.

Results: We identified 8,734 patients, of which 4.2% experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. of those in the inpatient and outpatient SHO groups), 31% experienced at least one SHO-related hospitalization, while 9% were treated in the ED without subsequent hospitalization. Approximately 79% of patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. The inpatient SHO patients stayed in the hospital, including time in the ED, for 1.7 days and incurred $3551 in costs. About one-third of patients were hospitalized again for SHO. Inpatient SHO patients incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the two other groups ($2084 vs $1313 and $1372), corresponding to 59% or 52% higher monthly costs for inpatient SHO patients.

Limitations: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders.

Conclusions: The burden associated with SHO is not negligible. About 4% of T1DM patients using basal-bolus insulin regimens are hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incur red at least $712 (52%) more in costs per month after their hospitalization than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T1DM.     

住院2型糖尿病患者发生低血糖的危险因素分析

目的:探讨2型糖尿病患者发生低血糖的相关危险因素,为临床糖尿病治疗过程中血糖安全达标、有效规避低血糖提供参考。方法:选择2010年4月–2011年12月于我院内分泌科住院的640例2型糖尿病患者,其中发生过明确低血糖的患者132例(低血糖组),未发生低血糖的患者508例(无低血糖组)。对两组患者的临床数据进行单因素χ2检验或Fisher精确概率分析和多因素logistic回归分析。结果:患者年龄、内生肌酐清除率(Ccr)、BMI、糖尿病病程以及住院天数是低血糖发生的独立危险因素(P<0.05)。结论:2型糖尿病患者较长的糖尿病病程、肾功能不全、年龄小、BMI过低均会增加低血糖发生风险,而由于住院期间的强化治疗,住院时间过长会增加低血糖的暴露。因此,对于具有上述高危因素的人群应积极预防低血糖。     

降糖药物与低血糖事件的相关性

目的调查实践中2型糖尿病患者使用降糖药物与低血糖事件发生的相关性。方法回顾总结兰州大学第二医院VIP糖尿病科2型糖尿病合并药物性低血糖患者的病例资料,对150例研究对象进行分析,收集了性别、年龄、降糖药物使用情况等数据,对收集的相关变量先进行单因素卡方检验,再将上述因素进行多因素Logistic回归分析。结果单因素分析结果显示有差异的变量是单用胰岛素、联合用药种类,多因素Logistic回归分析结果显示不同年龄组2型糖尿病患者低血糖的发生与单用胰岛素及联合用药种类有关系。结论不同年龄组的2型糖尿病患者发生药物性低血糖与单用胰岛素及降糖药物的联合用药种类相关。     

轻度亚临床甲状腺功能减退对2型糖尿病患者颈动脉内膜厚度的影响

目的 探讨轻度亚临床甲状腺功能减退对2型糖尿病患者血脂、血尿酸、颈动脉内膜厚度(CIMT)的影响.方法 选择2型糖尿病患者105例,根据促甲状腺激素(TSH)结果分成轻度亚临床甲状腺功能减退组(观察组,50例)和非甲状腺功能减退组(对照组,55例),比较两组血脂谱、血尿酸及颈动脉内膜厚度等指标.结果 两组间年龄、血压、体质量指数比较差异无统计学意义,血脂谱、血尿酸及颈动脉内膜厚度比较差异有统计学意义(P<0.05).Pearson单因素相关分析,患者的糖尿病病程、糖化血红蛋白、TSH、血尿酸、血肌酐与颈动脉内膜厚度存在相关性(P<0.05).多因素相关分析,TSH、尿酸与颈动脉内膜厚度密切相关(P<0.05).结论 TSH升高是2型糖尿病患者动脉粥样硬化的独立危险因素.     

Effectiveness of the SUGAR intervention on hypoglycaemia in elderly patients with type 2 diabetes: A pragmatic randomised controlled trial

BackgroundA pharmacist-led, individualised, educational intervention (SUGAR) was formulated to prevent hypoglycaemia among elderly patients with type 2 diabetes mellitus (T2DM) in Jordan.Objective(s)To evaluate the effectiveness of the SUGAR intervention added to usual care compared with usual care only in preventing hypoglycaemic attacks in elderly patients with T2DM in Jordan.MethodsA single-centre, pragmatic, open-label, randomised controlled trial with embedded process evaluation was conducted at the outpatient clinics of a hospital in Jordan. Elderly patients (≥65 years) with T2DM and on sulfonylurea, insulin, or at least three anti-diabetic medications were recruited and parallelly randomised to the SUGAR intervention with usual care or the control (usual care) groups. The primary outcome was the rate of total hypoglycaemic attacks per patient after 3 months from randomisation. Secondary outcomes included rate of hypoglycaemia subtypes, the incidence of any and subtypes of hypoglycaemia, hypoglycaemia-free survival probability, and incidence of fasting hyperglycaemia necessitating therapy modification. Outcomes were measured through glucose meters and diaries, assessed at 3 months, and analysed by intention to treat.ResultsA total of 212 participants (mean age 68.98 years, 58.96% men) were randomly allocated (106 in each group), with 190 (89.62%) participants completing the study. The mean of total hypoglycaemic attacks was less in the intervention group compared with the control group (3.91 [SD 7.65] vs. 6.87 [SD 11.99]; p < 0.0001) at three months. The intervention significantly reduced the rate of hypoglycaemia subtypes; the odds to experience any, severe, and symptomatic hypoglycaemia; and increased hypoglycaemia-free survival probability compared with the control group at three months. Incidence of fasting hyperglycaemia necessitating therapy modification was similar between groups.ConclusionsThe SUGAR intervention can prevent hypoglycaemia without increasing the risk of fasting hyperglycaemia warranting therapy adjustment in elderly Jordanians with T2DM.     

Association between hypoglycemia risk and hemoglobin A1C in patients with type 2 diabetes mellitus

Objective: To better manage type 2 diabetes mellitus (T2DM), the tradeoff between improved glycemic control and hypoglycemia should be evaluated. The purpose of this study was to assess the relationship between hypoglycemia and hemoglobin A1c (HbA1c) in a real-world population.

Research design and methods: Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) was a multi-center, observational study. Patients ≥30 years old using any oral anti-hyperglycemic agent were recruited from seven European and five Asian countries between 2006 and 2007. Hypoglycemia events were collected through patient-reported questionnaires. HbA1c data was collected through chart review. Logistic regression was performed to assess the relationship between hypoglycemia and the most proximate HbA1c levels adjusting for potential confounders (demographics, clinical variables, other medication use, and comorbid conditions).

Results: A total of 4399 patients were recruited and analyzed. Mean age was 60 years, 52% were male, and 75% were on sulfonylureas (S.U.s). Respectively, 37% or 42% of patients reported hypoglycemia in the past 6 (Asia) or 12 months (Europe) before recruitment. Prevalence of hypoglycemia increased significantly (33% to 40%) as HbA1c decreased (p?=?0.035). The same trend was also observed among S.U.-treated patients (p?<?0.01). After adjusting for confounders, hypoglycemia prevalence was significantly higher for HbA1c <7.0% (odds ratio [O.R.]?=?1.66 [95% C.I. 1.21, 2.28]; p?=?0.002) vs. HbA1c ≥10.0%.

Limitations: Our analyses pooled data from Asia and Europe, which differed in terms of the recall period for ascertaining hypoglycemia symptoms and the timing of latest HbA1c measure.

Conclusions: Lower HbA1c level was associated with higher hypoglycemia prevalence among S.U.-treated patients. HbA1c level should be taken into consideration when reporting hypoglycemia prevalence.     

Short-term cost-effectiveness of insulin detemir and insulin aspart in people with type 1 diabetes who are prone to recurrent severe hypoglycemia

Objective: Based on the data of the HypoAna trial (ClinicalTrials.gov NCT00346996), a short-term cost–effectiveness analysis was conducted comparing an all insulin analogue regimen with an all human insulin regimen in people with type 1 diabetes who are prone to recurrent severe hypoglycemia.

Methods: Clinical data from the HypoAna trial and Danish cost data related to the treatment of severe hypoglycemia were used to populate a 1-year cost–effectiveness analysis. Hypoglycemia quality-of-life data were based on previously published utility values, used to calculate the quality-adjusted life-years (QALYs) gained. Sensitivity analyses were conducted to test the robustness of the analysis. The main outcome measure was the incremental cost–effectiveness ratio (ICER).

Results: The insulin analogue regimen was associated with greater total costs compared with the human insulin regimen (20,418 DKK [1972 GBP] vs. 18,558 DKK [1793 GBP], respectively), primarily driven by the difference in insulin costs. Total costs for corrective actions for hypoglycemic events, however, were lower in the insulin analogue group (927 DKK [89 GBP]) compared with the human insulin group (1311 DKK [127 GBP]), primarily due to a lower event rate. QALYs were higher with insulin analogues vs. human insulin (difference 0.0672). The resulting ICER was 27,685 DKK (2674 GBP) per QALY gained, which is well below the generally accepted cost–effectiveness threshold.

Conclusions: The analysis shows that treating people with type 1 diabetes who are prone to recurrent severe hypoglycemia with an insulin analogue regimen is cost-effective compared with a human insulin regimen.     

A multicenter,epidemiological study of the treatment patterns,comorbidities and hypoglycemia events of patients with type 2 diabetes and moderate or severe chronic kidney disease – the ‘LEARN’ study

Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the ‘LEARN’ study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece.

Research design and methods ‘LEARN’ was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece.

Results Participants had a mean age of 69.1?±?10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA_1c)?≤?7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p?=?0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1?±?0.4) compared to patients receiving insulin only (0.9?±?1.7) (p?=?0.03).

Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis.