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Uric acid (UA) is the end product of purine nucleotide metabolism in the human body. Hyperuricemia is an abnormally high level of UA in the blood and may result in arthritis and gout. The prevalence of hyperuricemia has been increasing globally. Epidemiological studies have shown that UA levels are positively correlated with cardiovascular diseases, including hypertension, atherosclerosis, atrial fibrillation (AF), and heart failure (HF). Hyperuricemia promotes the occurrence and development of cardiovascular diseases by regulating molecular signals, such as inflammatory response, oxidative stress, insulin resistance/diabetes, endoplasmic reticulum stress, and endothelial dysfunction. Despite extensive research, the underlying molecular mechanisms are still unclear. Allopurinol, a xanthine oxidase (XO) inhibitor, has been shown to improve cardiovascular outcomes in patients with HF, coronary heart disease (CHD), type 2 diabetes (T2D), and left ventricular hypertrophy (LVH). Whether febuxostat, another XO inhibitor, can improve cardiovascular outcomes as well as allopurinol remains controversial. Furthermore, it is also not clear whether UA-lowering treatment (ULT) can benefit patients with asymptomatic hyperuricemia. In this review, we focus on the latest cellular and molecular findings of cardiovascular disease associated with hyperuricemia and clinical data about the efficacy of ULT in patients with cardiovascular disease.

Diabetes mellitus ranks among the top ten causes of mortality throughout the world [1,2]. With the rapid advancement of medicine, treatments without side effect for the long-term control of this disorder becomes important. Alternative therapies have recently received attention. Physical exercise in the control of diabetes has been criticised because an increase in glucagon and adrenaline secretion could raise the plasma glucose [3]. Acupuncture has been used in traditional Chinese medicine to relieve symptoms of diabetes mellitus for many years [4].The Zhongwan acupoint is located on the abdominal wall associated with the pancreas [5]. This area contains muscle and adipose tissue, both of which are insulin sensitive tissues. Electroacupuncture (EA) is widely used in traditional Chinese medicine because it combines the effects achieved with traditional needle acupuncture with those of massage [4]. It causes a prolonged contraction of the abdominal muscle fibres and ATP expenditure in addition to an increase in blood circulation resulting in faster glu- Diabetologia (1999) Summary Acupuncture at the Zhongwan acupoint has been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. Our study investigated the effect on plasma glucose of electroacupuncture applied at the Zhongwan acupoint in rat diabetic models. Plasma concentrations of insulin, glucagon and b-endorphin were also determined using radioimmunoassay. A decrease in plasma glucose was observed in rats after electroacupuncture (15 Hz, 10 mA) for 30 min at the Zhongwan acupoint. This was observed in normal rats and rat models with Type II (non-insulin-dependent) diabetes mellitus. No significant effect on plasma glucose was observed in rat models with Type I (insulin-dependent) diabetes mellitus; neither the streptozotocin (STZ)-induced diabetic rats nor the genetic (BB/W) rats. Further, the hypoglycaemic action of electroacupuncture stimulation disappeared in rats with insulin-resistance induced by an injection of human long-acting insulin repeated daily to cause the loss of tolbutamide-induced hypoglycaemia. An insulin-related action can thus be hypothesised. This hypothesis is supported by an increase in plasma insulin-like immunoreactivity after electroacupuncture stimulation in normal rats. Participation of glucagon was ruled out because there was no change in plasma glucagonlike immunoreactivity resulting from electroacupuncture stimulation. In addition to an increase in plasma b-endorphin-like immunoreactivity, the plasma glucose lowering action of electroacupuncture stimulation at Zhongwan acupoint was abolished by naloxone in a sufficient dose to block opioid receptors. Thus we suggest that electroacupuncture stimulation at the Zhongwan acupoint induces secretion of endogenous b-endorphin which reduces plasma glucose concentration in an insulin-dependent manner. [Diabetologia (1999) 42: 250±255]

To better understand the insulin-independent plasma glucose-lowering action of metformin, we used streptozotocin (STZ)-induced diabetic rats to investigate the possible mechanisms. Oral intake of metformin decreased the plasma glucose of STZ-induced diabetic rats with a parallel increase of plasma ␤-endorphin-like immunoreactivity (BER). Mediation of opioid -receptors in the action of metformin was identified by the blockade of receptors with antagonist in STZ-induced diabetic rats and the failure of action in opioid -receptor knockout diabetic mice. Release of BER from adrenal glands by metformin was characterized, using bilateral adrenalectomy and the release of BER from isolated adrenal medulla of STZ-induced diabetic rats. Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine. Reduction of the mRNA or protein levels of hepatic PEPCK was also impeded in the same group of STZ-induced diabetic rats. In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of ␤-endorphin secretion from adrenal glands to stimulate opioid -receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZinduced diabetic rats. Diabetes 55:819 -825, 2006

This article addresses the differences between the basic concepts of drug therapy in Chinese traditional medicine (CTM) and modern Western medicine. In ancient times, throughout the world, humans used plants as food and medicine. In Europe, chemistry developed rapidly after the influence of Paracelsus. Active principles were isolated from plants, and drugs were prepared in the salt form to use as medication. In China, several drugs isolated from plants have been prepared in the salt form in recent years, but herbal medication, developed in the ancient tradition, continued to be widely used in Chinese populations. Some theories such as the yin-yang theory and the five-element theory were commonly employed to explain the rationale for the use of CTM. In this review, hypertension and diabetes mellitus are used as examples to illustrate the applications of CTM. The notions of the "whole" and the use of "relative" rather than absolute are important concepts, which distinguish CTM from modern medicine.

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As frequent use of continuous glucose monitoring is associated with improved glycaemic control without increased hypoglycaemia it is important to overcome barriers, reinforce benefits and set realistic expectations for this technology in order to promote its more consistent and frequent use in individuals with Type 1 diabetes.

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