Diabetes is an inflammatory disease: evidence from traditional Chinese medicinesXie, W.; Du, L.
doi: 10.1111/j.1463-1326.2010.01336.xpmid: 21205111
Diabetes is usually associated with inflammation. Inflammation contributes to the development of diabetes. Traditional Chinese medicines (TCM) play an important role in lowering blood glucose and controlling inflammation. Many studies show that TCM with hypoglycaemic effects, for example Radix Astragali, Radix Rehmanniae, Radix Trichosanthis, Panax Ginseng, Fructus Schisandrae, Radix Ophiopogonis, Rhizoma Anemarrhenae, Radix Puerariae, Fructus Lycii, Poria, Rhizoma Coptidis, Rhizoma Dioscoreae, Rhizoma Polygonati, Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, Semen Trigonellae, Momordica charantia, Allium sativum, Opuntia stricta, Aloe vera, Cortex Cinnamomi, Rhizoma Curcumae Longae, and so on, have nearly independent anti‐inflammatory action. Antihyperglycaemic compounds, for example berberine, puerarin, quercetin, ferulic acid, astragaloside IV, curcumin, epigallocatechin gallate, resveratrol, tetrandrine, glycyrrhizin, emodin and baicalin, used in TCM also have anti‐inflammatory effects. These studies suggest that TCM might exert hypoglycaemic effects that are partly mediated by the anti‐inflammatory mechanisms. However, small amounts of TCM with potent anti‐inflammatory action does not have any hypoglycaemic effect. This indirectly indicates that diabetes may be a low‐grade inflammatory disease and potent regulation of inflammatory mediators may not be required. Studies of TCM add new evidences, which indicate that diabetes may be an inflammatory disease and slight or moderate inhibition of inflammation might be useful to prevent the development of diabetes. Through this review, we aim to develop more perspectives to indicate that diabetes may be an inflammatory disease and diverse TCM may share a common antidiabetic property: anti‐inflammatory action. Further studies should focus on and validate inflammation‐regulating targets of TCM that may be involved in inhibiting the development of diabetes.
Glucagon‐like peptide‐1‐based therapies and cardiovascular disease: looking beyond glycaemic controlAnagnostis, P.; Athyros, V. G.; Adamidou, F.; Panagiotou, A.; Kita, M.; Karagiannis, A.; Mikhailidis, D. P.
doi: 10.1111/j.1463-1326.2010.01345.xpmid: 21205117
Type 2 diabetes mellitus is a well‐established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation‐resistant incretin mimetic exenatide and the glucagon‐like peptide‐1 (GLP‐1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)‐4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP‐1. GLP‐1 exerts its glucose‐regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose‐dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP‐1 receptors (GLP‐1Rs), although GLP‐1R‐independent pathways have been reported. Except for the pancreatic islets, GLP‐1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP‐1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP‐1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti‐inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP‐4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo‐controlled trials. This review discusses the role of GLP‐1 on the cardiovascular system and addresses the impact of GLP‐1‐based therapies on CVD outcomes.
Therapies for diabetic dyslipidaemiaBell, D. S. H.; Al Badarin, F.; O’Keefe, J. H.
doi: 10.1111/j.1463-1326.2010.01342.xpmid: 21205114
Correction of diabetic dyslipidaemia in diabetic patients is the most important factor in reducing cardiac risk. Diabetic dyslipidaemia is characterized by elevated triglycerides, low total high‐density lipoprotein (HDL) and small dense low‐density lipoprotein (LDL) particles. The most important therapeutic goal in diabetic dyslipidaemia is correction of the non‐HDL‐cholesterol (HDL‐C) level. Glycaemic control with particular attention to postprandial glucose control plays a role not only in improving dyslipidaemia but also in lowering cardiac events. Pioglitazone is particularly effective for improving the manifestations of diabetic dyslipidaemia, in addition to its favorable effects on systemic inflammation and hyperglycaemia. Use of statins in addition to lifestyle change is recommended in most if not all type 2 diabetic patients and the goal should be to lower the LDL to a level recommended for the patient with existing cardiovascular disease (CVD) (non‐HDL‐C level <100 mg/dl). In addition, therapies for normalization of HDL and triglyceride levels should be deployed. Most patients with type 2 diabetes (T2D) will require combining a lipid‐lowering therapy with therapeutic lifestyle changes to achieve optimal lipid levels. Combinations usually include two or more of the following: a statin, nicotinic acid, omega‐3 fats and bile acid sequestrants (BASs). Fibrates may also be of use in diabetic patients with persistently elevated triglycerides and depressed HDL‐C levels, although their role in lowering adverse CV events is questionable.
Liraglutide, a once‐daily human glucagon‐like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetesGarber, A.; Henry, R. R.; Ratner, R.; Hale, P.; Chang, C. T.; Bode, B.
doi: 10.1111/j.1463-1326.2010.01356.xpmid: 21205128
Aims: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years.
Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium–glucose co‐transporter type 2, in Japanese subjects without and with type 2 diabetes mellitusKasichayanula, S.; Chang, M.; Hasegawa, M.; Liu, X.; Yamahira, N.; LaCreta, F. P.; Imai, Y.; Boulton, D. W.
doi: 10.1111/j.1463-1326.2011.01359.xpmid: 21226818
Aims: Dapagliflozin, a selective, orally active inhibitor of the renal sodium–glucose co‐transporter type 2 (SGLT2) is in development for the treatment of type 2 diabetes mellitus (T2DM). Here, the pharmacokinetics (PK) and pharmacodynamics (PD) of dapagliflozin were evaluated in healthy Japanese subjects and in Japanese subjects with T2DM.
Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetesBunck, M. C.; Eliasson, B.; Cornér, A.; Heine, R. J.; Shaginian, R. M.; Taskinen, M.‐R.; Yki‐Järvinen, H.; Smith, U.; Diamant, M.
doi: 10.1111/j.1463-1326.2010.01355.xpmid: 21205127
Preclinical studies suggest that incretin‐based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty‐nine metformin‐treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual‐energy X‐ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44‐week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44‐week therapy (LSmean ± s.e.m. between‐group difference −0.002 ± 0.007 g/cm2; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty‐four‐week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.