The therapeutic potential of insulin-mimetic vanadium complexes

Throughout the world, the number of patients suffering from diabetes mellitus (DM) is increasing on a daily basis, probably due to change in lifestyle. DM is mainly classified as either insulin-dependent Type 1 or non-insulin-dependent Type 2, according to the definition of WHO. To treat DM, which has many severe complications, several types of insulin preparations and synthetic drugs for Type 1 and Type 2 DM, respectively, have been developed and are in clinical use. However, there are several problems concerning the insulin preparations and synthetic drugs, such as physical and mental pain due to daily insulin injections and defects involving side effects, respectively. Consequently, a new class of therapeutic agents is anticipated. For this purpose, vanadium-containing complexes are expected to treat or improve both types of DM by using unique characteristics of the transition metal. In this article, the current state of research on insulin-mimetic vanadium complexes are reviewed, with special focus on the paramagnetic vanadyl (+4 oxidation state of vanadium) complexes with different coordination modes. To analyse the blood glucose-lowering effects of the vanadyl complexes, new results on the organ distribution and pharmacokinetic analysis of the vanadyl state in the blood of rats are also described.     

辛伐他丁治疗老Ⅱ型糖尿病脂代谢紊乱的疗效

目的：探讨辛伐他丁对老年Ⅱ型糖尿病脂代谢紊乱患者的疗效。方法：３０例老年Ⅱ型糖尿病脂代谢紊乱患者予辛伐他丁片５￣２０ｍｇ ｑｎ,用药４ｗｋ。结果：辛伐他丁降低ＴＣ２５％,ＬＤＬ－Ｃ降低２５％,降低ＴＧ２２．８％。ＨＤＬ－Ｃ降低者有升高作用,且降低ＴＣ／ＨＤＬ－Ｃ２１．８％,也降低载脂蛋白Ｂ１８％。对血糖水平无不良影响。结论：辛伐他丁用于老年Ⅱ型糖水病脂代谢异常患者安全、有效。     

肠道益生菌对2型糖尿病合并代谢综合征患者的临床疗效观察

目的：观察常规治疗联合培菲康对2型糖尿病合并代谢综合征患者血糖、血脂、血压、体重控制的临床疗效。方法：收集2015年4月1日—2015年6月30日期间在甘泉街道社区卫生服务中心门诊就诊的2型糖尿病合并代谢综合征患者100例,采用1：1配对分组（年龄、性别、基础疾病）法分为对照组和试验组各50例,对照组给予常规降糖、降脂、降压治疗,试验组加用培菲康840 mg,2次/d口服,疗程为6周。比较治疗前后两组血糖、血脂、血压、体重变化以及停药后6周的疗效差异。结果：6周后试验组与对照组相比血糖、血压、血脂、体质均未见明显差异（P>0.05）;然而停药6周后,两组空腹血糖、餐后2 h血糖、总胆固醇数值下降具有统计学意义（P<0.05）。结论：调节肠道菌群,能够改善代谢综合征患者血糖、血脂指标,远期疗效值得期待。     

喹诺酮类药物金属配合物的研究进展

目的对喹诺酮类药物的发展过程及其金属配合物的配位结构和活性等方面进行综述,为进一步研究喹诺酮类药物金属配合物提供科学依据。方法对相关文献进行归纳、总结和综述。结果喹诺酮类药物金属配合物的研究取得较快发展,但还存在着许多有待解决的问题。结论展望了喹诺酮类药物金属配合物研究的发展趋势。     

2型糖尿病合并非酒精性脂肪性肝病与代谢综合征的关系

目的分析2型糖尿病（type 2 diabetes mellitus,T2DM）合并非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）的代谢特点,探讨其与代谢综合征（metabolic syndrome,MS）及各组分的关系。方法160例T2DM患者分为2组,T2DMN组为T2DM合并NAFLD,84例;T2DM组为T2DM不伴NAFLD组,76例。通过分析2组之间病程、体重指数、血压、血脂、血糖及肝功能等指标,了解T2DM合并NAFLD的临床特点,比较两组符合MS及各组分的情况。结果2组患者性别、年龄、血压、糖尿病病程无显著差异,P〉0.05;T2DMN组BMI、TG、ALT、UA显著高于T2DM组,HDL-C低于T2DM组,P〈0.01;2组之间符合MS的比较,T2DMN组符合MS的为61.90%,T2DM组42.10%,P〈0.01。结论T2DM合并NAFLD易伴发MS。T2DM是否伴NAFLD的识别对T2DM有否心血管疾病（cardiovascular disease,CVD）风险的预测具有重要意义。     

The relationship between features of metabolic syndrome and blood adipocytokine concentrations in the morbid obese patients during dynamic weight loss

Bariatric surgery is the most effective method to achieve weight loss in obese subjects. The aim of this study was to evaluate some adipocytokines and insulin, as well as parameters of metabolic syndrome of the obese patients, for three and six months after vertical banded gastroplasty, in the time of dynamic weight loss. Seven males and two females aged 28 to 49 years, with long lasting simple obesity and the presence of metabolic syndrome, were studied. After surgical treatment the values of the body mass index, waist circumference, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, triglycerides, and blood concentrations of leptin decreased significantly. Before surgical operation of all obese patients no statistically significant correlations between studied parameters were noted. Three and six months later a lot of correlations between studied parameters appeared. In conclusion, (a) vertical-banded gastroplasty is a valuable method in treatment of obese subjects, leading to a significant decrease in body weight and improvement in some parameters of metabolic syndrome in a few months after surgery, (b) adipocytokines, together with an unknown gastric factor, may be key factors in the control of some features of the metabolic syndrome.     

吡格列酮治疗2型糖尿病合并代谢综合征的临床疗效观察

目的观察吡格列酮治疗2型糖尿病合并代谢综合征的临床疗效。方法选择68例患者随机分为研究组与对照组,各34例。两组患者均应用二甲双胍进行治疗,部分患者根据病情合用格列美脲,同时采用饮食、运动控制治疗。研究组则在上述基础治疗上加用吡格列酮30mgQd。结果研究组随访6个月时的HbA1c水平明显低于对照组（P〈0．05）HOMA—IR在随访3个月和6个月时研究组均明显低于对照组（P〈0．05）研究组HDL—c在随访3个月和6个月时均明显高于基线水平垆〈0．05）研究组DBP在随访6个月时明显低于对照组垆〈0．05）。结论吡格列酮可同时干预MS的多个指标,从而提高2型糖尿病合并代谢综合征的治疗效果。     

代谢综合征患者血清脂联素浓度与血脂的相关性研究

目的: 探讨代谢综合征患者血清脂联素水平与血脂的关系.方法: 选取代谢综合征患者35例,另选健康对照组20例,常规测量身高、体重,所有实验对象空腹采血离心取血清测定脂联素、甘油三酯(TG)、胆固醇、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C).结果: 与对照组相比,代谢综合征组血清脂联素水平显著降低(P<0.01),血清TG、CHOL、HDL-C、LDL-C、BMI、显著升高(P<0.01).Pearson相关性分析显示,在代谢综合征组中血清脂联素与TG、CHOL、LDL-C、BMI、年龄呈负相关,与HDL-C呈正相关(P<0.05).结论: 低血清脂联素水平与脂类代谢紊乱密切相关.     

Managing the combination of nonalcoholic fatty liver disease and metabolic syndrome

Introduction: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies.

Areas covered: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience.

Expert opinion: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory.     

The correlated study of hyperuricemia and metabolic syndromes among males of Han ethnicity in the Xinjiang Uygur Autonomous Region, China

This study investigates the relationship between hyperuricemia and metabolic syndrome (MS) among males of Han ethnicity in the Xinjiang Uygur Autonomous Region, China. The blood samples were collected from January to May, 2006 in Urumqi. It included 1496 subjects with ages between 20 to 70 years. All these subjects had physical examinations, blood pressure (BP) measurement and analysis for serum uric acid (SUA), fasting blood sugar (FBS), serum triglyceride (TG), serum total cholesterol (TC), serum high density lipoprotein (HDL-C) and serum low density lipoprotein (LDL-C) as well as biochemistry assay. The Data were analyzed using the Pearson Chi-Square Test, Independent-Samples T-Test and the Mantel-Haenszel Test for linear trend, respectively. The results show that the prevalence of MS in the present study was 18%. Blood pressure, fasting blood sugar, body mass index (BMI), waist/hip ratio(WHR), TG, TC and LDL-C were significantly higher in the hyperuricemic group than in normal group and these parameters were strongly related to serum uric acid levels. The components of metabolic syndrome such as obesity, hyperglycemia, hypertension and dyslipidemia had a close correlation with SUA. The Odds ratios of these metabolic diseases in the hyperuricemic group were 3.097 times, 2.633 times, 2.226 times and 3.058 times of the normal SUA group, respectively. They all have a positive correlation with hyperuricemia. Hyperuricemia is closely linked to the various components of the metabolic syndrome. More emphasis should be put on the evolving control and prevalence of hyperuricemia and metabolic syndrome among males of Han ethnicity in Xinjiang. __________ Translated from Journal of Xinjiang Medical University, 2007, 30(6): 535–538 [译自: 新疆医科大学学报]     

Rimonabant: the evidence for its use in the treatment of obesity and the metabolic syndrome

Introduction:

Obesity and overweight affect over 1 billion people worldwide and are leading causes of morbidity and mortality. Clinical features of obesity converge with those of the metabolic syndrome and type 2 diabetes, greatly increasing the risk of long-term adverse outcomes.

Aims:

To review the evidence on rimonabant, a novel CB1 receptor antagonist, for the treatment of obese and overweight patients.

Evidence review:

There is clear evidence that rimonabant 20 mg/day in conjunction with a hypocaloric diet causes a mean weight loss of 4.6 kg in obese and overweight patients after 1 year’s treatment, with approximately 50% of patients achieving a weight loss of ≥5%. One study demonstrated that weight loss is maintained for up to 2 years. The drug also improves lipid and glycemic cardiovascular risk factors, including high-density lipoprotein cholesterol and insulin resistance, and reduces waist circumference, thus reducing the prevalence of metabolic syndrome. Treatment of obese and overweight diabetic patients with rimonabant decreases glycosylated hemoglobin (HbA_1c), including patients previously untreated for diabetes. The effect of rimonabant appears to be partly independent of weight loss.Rimonabant 20 mg/day is generally well tolerated, with mild to moderate transient adverse effects including nausea, diarrhea, dizziness, and anxiety. Approximately 14% of patients receiving rimonabant 20 mg/day discontinued due to adverse effects, primarily depressed mood, although overall rates of depression did not differ significantly compared with placebo.

Place in therapy:

The evidence supports the use of rimonabant 20 mg/day along with dietary modification to reduce cardiovascular risk factors in obese and overweight patients, including those with diabetes. The drug is contraindicated in patients receiving antidepressants. Long-term data on cardiovascular outcomes, morbidity, and mortality are eagerly awaited.     

Novel peroxisome proliferator-activated receptor ligands for Type 2 diabetes and the metabolic syndrome

As the incidence of Type 2 diabetes has reached near epidemic proportions, the quest for novel therapies to combat this disorder has intensified dramatically. In recent years, the peroxisome proliferator-activated receptor (PPAR) family has received tremendous attention as perhaps an ideal target class to address the multiple metabolic anomalies associated with the diabetic state. This review focuses on a variety of novel PPAR approaches currently being investigated for Type 2 diabetes or the metabolic syndrome, including the highly potent selective PPAR agonists, PPAR combination agonists and alternative PPAR ligands.     

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

Tributyltin (TBT), a proven environmental obesogen, functions as a nanomolar agonist of the peroxisome proliferator activated receptor‐γ (PPARγ). However, the adverse effects of TBT on metabolism are incompletely understood. In this study, male ICR mice were administered TBT (5 and 50 μg·kg^–1) by an intraperitoneal injection once every 3 days for 30 days from 28 days of age and bred for another 30 days after the last administration of TBT. We analyzed the effects of these exposures on the fat depot weights, serum lipid profile, serum leptin and adiponectin, hepatic lipid accumulation, and activity of AKT in the liver and skeletal muscle isolated from mice 8 mins after receiving an insulin injection. Pubertal exposure to TBTCl resulted in a higher body weight, increased epididymal and liver fat accumulation, hyperlipidemia, an elevated low‐density lipoprotein/high‐density lipoprotein ratio, serum adiponectin deficiency, worse glucose tolerance, and lower insulin‐dependent AKT phosphorylation in the liver and muscle in mice. These results showed that TBT exposure induced peripheral insulin resistance and metabolic syndrome in mice.     

Synthetic agents in the context of metabolic/bariatric surgery: expanding the scope and impact of diabetes drug discovery

Type 2 diabetes (T2D) – particularly with concurrent obesity (‘diabesity’) – is an intensifying global public-health problem. Medical needs and market opportunities in the T2D space have propelled discovery efforts aimed at inventing new synthetic T2D drugs differentiable by improved safety and efficacy and/or the ability to modulate emerging T2D targets. Particularly for moderately and severely obese individuals, weight-loss (bariatric) surgery offers an effective means of reducing obesity-driven T2D that is superior in many respects to medical T2D management. Yet, not all overweight or obese individuals with T2D qualify for bariatric surgery, and current healthcare resources are inadequate for applying surgical T2D control to more than a very small segment of qualified patients. Bariatric surgery is no guarantee of ‘curative’ T2D abrogation, significant rates of T2D non-remission or re-emergence having been observed in diabesity patients following bariatric procedures. Preoperative glucose control by oral hypoglycemic drugs reduces the chance of T2D recurrence post-surgery, and diabesity patients in whom glycemic indices have been improved by bariatric surgery may still require some level of T2D pharmacotherapy. Laboratory and clinical data indicate that synthetic T2D drugs can improve T2D-related outcomes following bariatric procedures, and current T2D drug-discovery efforts are being informed by the metabolic advantages associated with bariatric surgery. These circumstances intensify the need for and extend the impact of T2D drug discovery by demonstrating multiple levels of interplay between medical and surgical approaches to improve the health of individuals with diabesity and, perhaps, approach the overarching goal of decreasing long-term cardiovascular mortality.     

2型糖尿病和代谢综合征对男性冠心病的心肌结构和微血管的影响

目的研究2型糖尿病和代谢综合症对男性冠心病的心肌结构和微血管的影响。方法2006年2月至2010年2月选择了92例男性冠状动脉搭桥手术的患者,进行生化和心脏指标检测和组织学分析。结果3组中心静脉压、肺毛细血管楔压、心脏指数、射血分数、二尖瓣室间隔比值之间的差异具有统计学差异（P〈0．05）、二尖瓣E／E在代谢综合征和糖尿病患者的差别没有统计学意义（P〉0．05）。心肌细胞纤维化、心肌细胞宽度、毛细血管长度密度、扩散半径在3组之间无差异（P〉0．05）。动脉管壁面积／圆周率在3组之间的差异具有统计学意义（P〈0．05）。结论中心静脉压、肺毛细血管楔压、心脏指数、射血分数、二尖瓣室间隔比值不依赖于心肌细胞宽度、毛细血管长度密度、扩散半径的改变。     

糖尿病的诊治与进展--糖尿病与临床各科的关系

目的：介绍近年来的糖尿病诊治新概念和进展。方珐：以国内外相关文献为基础进行分析和归纳。结果与结论：随着糖尿病研究的深人和认识的加深，糖尿病的诊治已经跃上了一个新的台阶。     

The pharmacological management of metabolic syndrome

Introduction: The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice.

Areas covered: A Medline literature search was performed to identify clinical trials and meta-analyses related to the therapy of dyslipidemia, arterial hypertension, glucose metabolism and obesity published in the past decade.

Expert commentary: Our recommendation for first-line pharmacological are statins for dyslipidemia, renin-angiotensin-aldosteron system inhibitors for arterial hypertension, metformin or sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1RAs) for glucose intolerance, and the GLP-1RA liraglutide for achieving body weight and waist circumference reduction.     

The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus

Introduction: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled on these medications and who are undergoing diet and lifestyle modification. GLP-1RAs glucose-dependently increase insulin secretion, decrease glucagon secretion, and slow gastric emptying, thereby improving glycemic control. GLP-1RAs are associated with body weight benefits and low rates of hypoglycemia which are welcome in patients with T2DM.

Areas covered: The authors describe the identification of GLP-1RAs as suitable targets for modification with structure-inducing probe technology to improve stability and resistance to proteolytic degradation. Clinical studies have assessed lixisenatide across > 5000 patients as a monotherapy or add-on to a variety of commonly used antidiabetic medications. These studies highlighted the effects of lixisenatide on gastric emptying, explaining its particular improvements in postprandial plasma glucose (PPG) excursions and underscoring its efficacy in combination with insulin glargine. Lixisenatide was well tolerated, with nausea and vomiting being the most frequently reported adverse events.

Expert opinion: The once-daily administration of lixisenatide as well as its substantial sustained effect on gastric emptying and, hence, PPG excursions are all important features compared with the other GLP-1RAs. The combination of two injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA that curtails PPG excursions, is clinically valuable and could differentiate lixisenatide from other GLP-1RAs, especially from those continuously acting GLP-1RAs with little effect on gastric emptying and PPG excursions.