Mechanisms of insulin resistance caused by nutrient toxicity.

Insulin resistance, the impaired action of insulin, has been linked to many important consequences, including Type 2 diabetes, hypertension, dyslipidemia, acanthosis nigricans and polycystic ovarian syndrome. Although there are some genetic causes for insulin resistance, the most common cause is an excess of nutrition a condition called "Nutrient Toxicity". Both excess glucose and excess fat can cause insulin resistance in muscle and fat tissues and excess fat can cause insulin resistance in the liver. High fat feeding and fat infusion rapidly lead to the development of insulin resistance caused by impairment in glucose transport. Other studies have shown defects in insulin signaling possibly secondary to activation of Protein Kinase C resulting from the accumulation of active fatty acyl CoA's. Glucose toxicity has been studied both in vivo and in vitro. In vivo it has been shown that rats over-expressing the gluconeogenic enzyme Phosphoenol Pyruvate Carboxykinase (PEPCK) develop insulin resistance in fat and muscle tissues and some features of the metabolic syndrome including mild obesity and dyslipidemia. Excess glucose entry in fat cells results in increased flux through the hexosamine biosynthesis pathway leading to activation of protein kinase C and impairment of glucose transport. Obesity resulting from excess nutrient intake can also cause insulin resistance by an increase in the production of agents that impair insulin action such as TNFalpha and resistin and a decrease in the production of an insulin sensitizing compound adiponectin. Both glucose and free fatty acids acutely stimulate insulin secretion but chronic exposure to high levels of either nutrient leads to impairment of beta cell function. The combination of insulin resistance and beta cell failure leads to diabetes. Nutrient toxicity is thus the driving cause of the diabetes epidemic that is being recorded around the world.     

短期强化胰岛素治疗对高血糖毒性作用的影响

本试验对41例空腹血糖≥15mmol／L，餐后血糖≥16．8mmol／L的2型糖尿病患者进行短期胰岛素强化治疗(IIT)，治疗前后行糖负荷试验，并以放免法测胰岛素原、C肽。结果表明IIT降低空腹及餐后胰岛素原水平，改善β细胞功能。     

Energy expenditure of genuine laughter

OBJECTIVE: To measure energy expenditure (EE) and heart rate (HR) during genuine laughter. DESIGN: Experimental trial of viewing film clips in four cycles either intended to evoke laughter (humorous -10 min) or unlikely to elicit laughter (not humorous -5 min) under strictly controlled conditions of a whole-room indirect calorimeter equipped with audio recording system. PARTICIPANTS: Forty five adult friend dyads in either same-sex male (n=7), same-sex female (n=21) and mix-sex male-female (n=17); age 18-34 years; body mass index 24.7+/-4.9 (range 17.9-41.1). MEASUREMENTS: Energy expenditure in a whole-room indirect calorimeter, HR using Polar HR monitor. Laugh rate, duration and type from digitized audio data using a computerized system and synchronized with HR and EE results. RESULTS: Laughter EE was 0.79+/-1.30 kJ/min (0.19+/-0.31 kcal/min) higher than resting EE (P<0.001, 95% confidence interval=0.75-0.88 kJ/min), ranging from -2.52 to 9.67 kJ/min (-0.60-2.31 kcal/min). Heart rate during laughter segments increased above resting by 2.1+/-3.8 beats/min, ranging from -7.6 to 26.8 beats/min. Laughter EE was correlated with HR (r (s)=0.250, P<0.01). Both laughter EE and HR were positively correlated with laughter duration (r (s)=0.282 and 0.337, both P<0.001) and rate (r(s)=0.256 and 0.298, both P<0.001). CONCLUSION: Genuine voiced laughter causes a 10-20% increase in EE and HR above resting values, which means that 10-15 min of laughter per day could increase total EE by 40-170 kJ (10-40 kcal).     

新诊断2型糖尿病患者糖毒条件下胰岛素敏感性与胰岛素分泌功能的观察

目的比较不同HbA1c水平的新诊断T2DM患者血糖、IS与胰岛素分泌功能、慢性并发症等情况。方法选取新诊断T2DM患者210例,根据HbA1c水平分为3组,用稳态模型胰岛素抵抗指数(HOMA-IR)、定量胰岛素敏感指数(QUICKI)、OGTT胰岛素敏感指数(OGIS)评估IS,HOMA-β、AUCIns及AUCR评估胰岛素分泌功能。对HbA1c的影响因素进行逐步多元回归分析。经多个独立样本非参数检验比较各组慢性并发症发生率。结果组间比较显示,随着HbA1c的升高,各时点血糖均明显升高,FIns及餐后2hIns水平明显下降。OGIS、HOMA-β、AUCIns及AUCR均显著下降(P<0.01)。HbA1c与2hPG呈显著正相关(r=0.675,P<0.01),与HOMA-β、OGIS呈显著负相关(r=-0.632,-0.578,P<0.01)。各组慢性并发症发生率均较高,但差异无统计学意义(P>0.05)。结论新诊断T2DM患者已处在高HbA1c水平,IS显著下降,胰岛分泌功能已明显受损,慢性并发症发生率高。     

The problem of the Romano-Ward syndrome--misinterpretation as genuine epilepsy]

It is reported on a case of Romano-Ward-syndrome in a 40-year-old female patient. The problems of the most frequent false interpretation as idiopathic epilepsy as well as the differential-diagnostic considerations concerning the exclusion of symptomatic QT(U)-elongations in the ECG are entered. The pathomechanisms which perhaps are the basis of the syndrome are discussed.     

非肿瘤性胰腺真性囊肿21例诊治体会

目的 探讨非肿瘤性胰腺真性囊肿的诊断和治疗.方法 回顾性分析1999年6月至2006年9月收治的21例非肿瘤性胰腺真性囊肿患者的临床病理资料及随访结果.结果 21例患者中,男3例,女18例,男女比例1:6;年龄24～77岁,平均47岁.12例无任何症状和体征,9例有症状.实验室检查均未见异常.行B超、ERCP、CT、MRI检查分别有21例、5例、21例、和4例,诊断准确率分别为0%、40%、19%和50%.20例行手术治疗,1例行剖腹探查、活组织检查.5例术后出现胸腔积液,其中3例发胰瘘,经治疗后痊愈出院.病理检查浆液性囊肿15例、潴留性囊肿3例、黏液性囊肿2例、淋巴上皮样囊肿1例.本组2例失访,19例获随访,随访时间8个月～7年,除1例因脑出血死亡,其余均健在,无复发.结论非肿瘤性胰腺真性囊肿好发于中年女性,无特征性临床表现,术前诊断准确率较低.对无症状患者不需手术治疗.有症状的、且影像学上不能与囊性肿瘤鉴别或随访期囊肿有增大趋势者宜手术治疗.     

非肿瘤性胰腺真性囊肿21例诊治体会

目的探讨非肿瘤性胰腺真性囊肿的诊断和治疗。方法回顾性分析1999年6月至2006年9月收治的21例非肿瘤性胰腺真性囊肿患者的临床病理资料及随访结果。结果21例患者中，男3例，女18例，男女比例1：6；年龄24～77岁，平均47岁。12例无任何症状和体征，9例有症状。实验室检查均未见异常。行B超、ERCP、CT、MRI检查分别有21例、5例、21例和4例，诊断准确率分别为0％、40％、19％和50％。20例行手术治疗，1例行剖腹探查、活组织检查。5例术后出现胸腔积液，其中3例并发胰瘘，经治疗后痊愈出院。病理检查浆液性囊肿15例、潴留性囊肿3例、黏液性囊肿2例、淋巴上皮样囊肿1例。本组2例失访，19例获随访，随访时间8个月～7年，除1例因脑出血死亡，其余均健在，无复发。结论非肿瘤性胰腺真性囊肿好发于中年女性，无特征性临床表现，术前诊断准确率较低。对无症状患者不需手术治疗。有症状的、且影像学上不能与囊性肿瘤鉴别或随访期囊肿有增大趋势者宜手术治疗。     

Radical surgery under genuine direct vision for the treatment of Budd-Chiari syndrome

BACKGROUND: Budd-Chiari syndrome (BCS) develops with complete or incomplete obstruction of the hepatic veins (HV), the super hepatic inferior vena cava (IVC), or both. Various methods have been reported regarding the treatment of BCS. In this article, we present our preliminary experience with radical surgery in the treatment of Budd-Chiari syndrome under genuine direct vision. METHODS: In 13 patients aged from 17 to 48 years, the disease lasted from 3 months to 5 years. Membranous obstruction of the inferior vena cava (IVC) was observed in 3 patients, right hepatic venous (HV) membrane in 1, IVC membrane with distal thrombosis in 6, long-segment thrombosis of the IVC in 2, and IVC thrombosis caused by retroperitoneal tumor extending to the right atrium in 1. RESULTS: All lesions were successfully resected. Extracorporeal circulation was used in one patient, and the cell saver in 2 patients. No blood transfusion was given except for 3 patients receiving blood transfusion of 2000, 400, and 400 ml, respectively. One patient died of renal failure during the postoperative period. Signs and symptoms disappeared after the operation in the remaining patients. CONCLUSION: This new radical surgery gives access to the lesions under clear direct vision in further facilitating the correction needed.     

Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity.

Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently-diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin-treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity".     

激素在儿童支原体感染性大叶性肺炎中的应用

目的 探讨糖皮质激素佐治儿童支原体感染性大叶性肺炎的临床疗效.方法 将129例支原体感性大叶性肺炎患儿分为观察组72例和对照组57例.对照组用红霉素(第 1周)加阿奇霉素(第2～4周)治疗,观察组在此基础上加输甲泼尼龙1～2 mg/(kg*d),2～3 d,后改口服泼尼松1～2 mg/(kg*d),3～4 d.对比两组患儿发热、咳嗽、肺部啰音消退时间和治愈率.结果 同对照组相比,观察组退热时间、止咳时间、肺部啰音消退时间均缩短,差异均有统计学意义(P<0.01);观察组治愈率(79.17%)明显高于对照组(59.65%),两者相比差异有统计学意义(P<0.05).结论 早期应用糖皮质激素佐治儿童肺炎支原体感染性大叶性肺炎可较快缓解临床症状,缩短病程,提高治愈率.