Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

INTRODUCTION: Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of alpha-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation. RESULTS AND DISCUSSION: Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events. CONCLUSION: Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.     

急性脑血管病患者应激性高血糖、血清钾、钠、氯的变化及其与中风类型、病情轻重、预后关系

目的探讨急性脑血管病患者应激性高血糖、血清钾、钠、氯的变化及其与中风类型、病情轻重、预后关系。方法本文对我院神经内科2004年6月～2005年6月住院急性脑血管病患者248例进行研究，其中出血性中风89例，缺血性中风159例，于入院次日晨检测空腹血糖、血清钾、钠、氯，观察血糖、血钠、血氯、血钾值的变化及其与脑卒中类型、病情轻重、预后关系。结果（1）急性脑血管病患者易出现应激性高血糖、低钠血症、低氯血症、低钾血症；（2）出血性中风血糖明显高于缺血性中风；高血糖组死亡率明显高于非高血糖组；死亡组的血糖均值亦显著高于存活组；统计学上差异有显著性。（3）出血性中风低血钠、低血氯的发生率明显高于缺血性中风，统计学上差异有显著性；低血钠、低血氯组中的中、重度患者显著多于正常血钠、血氯组；与正常血钠、血氯组相比，高血钠、高血氯组患者在中风类型、病情轻重及预后方面差异均无显著性，但血钠、血氯显著升高时，死亡率明显增加。与正常血钾组相比，低血钾组中患者在中风类型、病情及预后方面差异无显著性，但血钾明显降低时，病死率增加。高血钾组患者在中风类型、病情轻重和正常血钾组相比差异无显著性，但病死率则明显高于正常血钾组。结论急性脑血管病患者存在应激反应，急性脑血管病患者应激性高血糖、低钠血症、低氯血症可以作为判断急性脑血管病病情、预后评估的指标之一。高钠血症、高氯血症、高钾血症、低钾血症与中风类型、病情及预后方面差异无显著性，但当出现严重的高钠血症、高氯血症、高钾血症、低钾血症时，病死率明显增加。     

Ultrastructural studies of the neurovascular unit reveal enhanced endothelial transcytosis in hyperglycemia-enhanced hemorrhagic transformation after stroke

AimsPre‐existing hyperglycemia (HG) aggravates the breakdown of blood–brain barrier (BBB) and increases the risk of hemorrhagic transformation (HT) after acute ischemic stroke in both animal models and patients. To date, HG‐induced ultrastructural changes of brain microvascular endothelial cells (BMECs) and the mechanisms underlying HG‐enhanced HT after ischemic stroke are poorly understood.MethodsWe used a mouse model of mild brain ischemia/reperfusion to investigate HG‐induced ultrastructural changes of BMECs that contribute to the impairment of BBB integrity after stroke. Adult male mice received systemic glucose administration 15 min before middle cerebral artery occlusion (MCAO) for 20 min. Ultrastructural characteristics of BMECs were evaluated using two‐dimensional and three‐dimensional electron microscopy and quantitatively analyzed.ResultsMice with acute HG had exacerbated BBB disruption and larger brain infarcts compared to mice with normoglycemia (NG) after MCAO and 4 h of reperfusion, as assessed by brain extravasation of the Evans blue dye and microtubule‐associated protein 2 immunostaining. Electron microscopy further revealed that HG mice had more endothelial vesicles in the striatal neurovascular unit than NG mice, which may account for their deterioration of BBB impairment. In contrast with enhanced endothelial transcytosis, paracellular tight junction ultrastructure was not disrupted after this mild ischemia/reperfusion insult or altered upon HG. Consistent with the observed increase of endothelial vesicles, transcytosis‐related proteins caveolin‐1, clathrin, and hypoxia‐inducible factor (HIF)‐1α were upregulated by HG after MCAO and reperfusion.ConclusionOur study provides solid structural evidence to understand the role of endothelial transcytosis in HG‐elicited BBB hyperpermeability. Enhanced transcytosis occurs prior to the physical breakdown of BMECs and is a promising therapeutic target to preserve BBB integrity.     

不同碳水化合物肠内营养液对应激性高血糖患者早期血糖水平与预后的影响

目的观察不同的碳水化合物肠内营养液［肠内营养乳剂（TPF-D）和肠内营养混悬液（TPF）］用于早期肠内营养对应激性高血糖患者血糖水平与预后的影响,探讨其作为应激性高血糖患者早期肠内营养制剂的临床可行性。 方法选入2020年6至10月徐州医科大学附属医院急诊ICU收治的合并应激性高血糖的患者为研究对象。根据入排标准,最终71例患者纳入研究,随机数字表法将其分为观察组（35例,鼻饲TPF-D）和对照组（36例,鼻饲TPF）。收集患者一般资料,包括性别、年龄、急性生理与慢性健康状况（APACHE Ⅱ）评分;记录患者第1、3、7天每4小时一次血糖数据,并计算平均血糖值（GLU_AVE）、平均血糖波动幅度（GLU_MAGE）;计算治疗后3、7 d胰岛素应用总量;监测患者第1、7天相关营养指标变化,如总蛋白（TP）、白蛋白（ALB）、前白蛋白（PA）;记录胃肠道并发症（如反流、呕吐、腹泻、腹胀等）、ICU住院时间及28 d病死率。 结果（1）2组性别比例、年龄、APACHE Ⅱ评分比较,差异均无统计学意义（P＞0.05）。（2）2组第1、3、7天GLU_AVE及第1、3天GLU_MAGE比较,差异均无统计学意义（P＞0.05）;观察组第7天GLU_MAGE显著低于对照组,差异有统计学意义［（0.72±0.08）mmol/L vs（1.56±0.10）mmol/L,t=6.22,P=0.02］。（3）观察组治疗3、7 d胰岛素应用总量显著低于对照组,差异均有统计学意义［（60.40±39.80）U vs（102.70±49.60）U,t=0.17,P=0.02;（110.50±43.30）U vs（202.80±56.40）U,t=2.52,P=0.01］。（4）2组第1、7天TP、PA、ALB比较,差异均无统计学意义（P＞0.05）。（5）2组胃肠道并发症、ICU住院时间、28 d病死率比较,差异均无统计学意义（P＞0.05）。 结论应激性高血糖患者早期营养中,TPF-D较TPF能更好地降低血糖变异性,控制血糖波动幅度,并减少临床中胰岛素用量,但不影响预后。     

应激性血糖升高比值对急性心力衰竭患者预后的评估价值

目的:探究应激性血糖升高比值（stress hyperglycemia ratio,SHR）对急性心力衰竭（acute heart failure,AHF）患者预后的预测价值。方法:回顾性纳入2016年12月至2019年1月在上海交通大学附属第六人民医院急诊科就诊的AHF患者,收集临床资料,计算SHR,SHR=入院即刻血糖（mmol/L）/[（1.59×HbA1c）-2.59]。根据患者1年内的生存情况,分为死亡组和存活组,采用Logistic回归方法分析影响患者死亡的危险因素,并根据SHR中位数分组绘制Kaplan-Meier曲线。结果:共纳入符合标准的患者307例,年龄83（74,87）岁,其中男性153例。死亡组年龄、SHR及N末端B型利钠肽原（N-terminal prohormone of brain natriuretic peptide,NT-proBNP）高于存活组[84(78,88)岁 vs 82(72,86)岁、1.11(0.91,1.51) vs 1.02(0.86,1.27)、5 351(2 098,14 039) μg/L vs 4 243(2 294,7 565)μg/L],左心室射血分数（left ventricular ejection fraction,LVEF）低于存活组[53(45,57) % vs 58(44,64)%],差异有统计学意义（ P<0.05）;Logistic回归分析结果提示SHR水平升高是AHF患者1年死亡的独立危险因素（ OR=2.397,95% CI：1.285~4.471, P<0.05）。以SHR中位数分组绘制生存曲线,高SHR组累积生存率低,差异有统计学意义（ P<0.05）。 结论:SHR能够识别危重的AHF患者,是AHF患者死亡的独立危险因素。     

Labeling of pancreatic glycogen by d-[U-14C]glucose in hyperglycemic rats

Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic islets, but not so in acinar pancreatic cells. We investigated whether advantage could be taken of such a situation in the perspective of the noninvasive imaging of the endocrine pancreas. Control rats or animals injected with streptozotocin (STZ) were infused with solutions of d-glucose mixed with a tracer amount of d-[U-¹⁴C]glucose, and the radio-active glycogen content of both liver and pancreas was then measured. After 48 h of infusion, the radio-active glycogen content of the pancreas was 30 times lower in STZ rats than in control animals, coinciding with a 50 times lower insulin content. In the control rats, a sizable labeling of pancreatic glycogen was also recorded when d-[U-¹⁴C]glucose was infused for only the last 4 h of unlabeled d-glucose infusion; such a labeling was not decreased when the animals were further infused for 1 h with only the unlabeled hexose. Moreover, a pronounced difference in the pancreatic gland and blood radioactive content of control rats was still observed when the hyperglycemic animals were killed only 40 min after the iv injection of d-[U-¹⁴C]glucose. In STZ rats transplanted with islets and later infused with d-[U-¹⁴C]glucose, the total radioactive content and radioactive glycogen content were both much higher in the transplanted islets than in the pancreatic gland. These results allow one to define the conditions under which the administration of either 2-deoxy-2-[¹⁸F]fluoro-d-glucose or ¹¹C-labeled d-glucose could conceivably be used to favor the selective labeling of the endocrine, as distinct from exocrine, pancreas.     

Extra-intestinal symptoms in patients with irritable bowel syndrome: related to high total IgE levels and atopic sensitization?

Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain.     

Continuous Glucose Monitoring Versus Capillary Point-of-Care Testing for Inpatient Glycemic Control in Type 2 Diabetes Patients Hospitalized in the General Ward and Treated With a Basal Bolus Insulin Regimen

Background:

Continuous glucose monitoring (CGM) may improve the management of patients with type 2 diabetes hospitalized in the general ward by facilitating the detection of hyper- and hypoglycemic episodes. However, the lack of data on the accuracy and safety of CGM have limited its application.

Methods:

A prospective pilot study was conducted including 38 patients hospitalized in the general ward with a known diagnosis of type 2 diabetes mellitus (DM) and hyperglycemic individuals without a history of DM with a blood sugar of 140-400 mg on admission treated with a basal bolus insulin regimen. Inpatient glycemic control and the incidence of hypoglycemic episodes were compared between detection by CGM of interstitial fluid for up to 6 days and point-of-care (POC) capillary blood glucose monitoring performed pre- and postprandially, before bedtime and at 3 am.

Results:

No differences in average daily glucose levels were observed between CGM and POC (176.2 ± 33.9 vs 176.6 ± 33.7 mg/dl, P = .828). However, CGM detected a higher number of hypoglycemic episodes than POC (55 vs 12, P < .01). Glucose measurements were clinically valid, with 91.9% of patients falling within the Clarke error grid A and B zones.

Conclusions:

Our preliminary results indicate that the use of CGM in type 2 patients hospitalized in the general ward provides accurate estimation of blood sugar levels and is more effective than POC for the detection of hypoglycemic episodes and asymptomatic hypoglycemia.     

Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: a randomized,double-blind,placebo-controlled trial

We assessed the effect of multi-species probiotic mixture on the changes in fecal microbiota and irritable bowel syndrome (IBS) symptoms. Eighty-one IBS patients were randomly assigned to receive either probiotic mixture (n = 39; containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium breve, B. actis, B. longum, and Streptococcus thermophilus) or placebo (n = 42) for 4 weeks. A questionnaire regarding general symptom relief was administered. The change in total symptom scores (sum of 10 IBS symptoms) and subtotal scores in 4 domains (pain, constipation, diarrhea, and bloating/gas) were evaluated. The change in fecal flora was determined by quantitative real-time PCR. The concentration of probiotic strains significantly increased after ingestion in probiotics group (B. bifidum, p = 0.043; B. lactis, p<0.001; L. acidophilus, p = 0.016; L. rhamnosus, p<0.001). The proportion of patients with adequate symptom relief was higher in probiotics group than in placebo group (74.4% vs 61.9%, p = 0.230). The decrease in total symptom score over time was not significantly different between the groups (p = 0.703). Among subtotal scores of 4 IBS symptom domains, the time effect was significantly different for diarrhea-symptom score between the groups (p = 0.017). A 4-week administration of multi-species probiotic mixture significantly increased the fecal concentration of most probiotic strains and improved diarrhea-symptom scores in IBS patients.