Current Diabetes Reviews - Volume 6, Issue 4, 2010

Type 2 diabetes (T2D) is associated with increased cardiovascular disease and mortality. Most diabetes treatments have not proven to reduce this risk and may be associated with worsening of specific cardiovascular risk factors. GLP-1 receptor agonists (GLP-1R agonists) are new incretin-based therapies for the treatment of T2D. They improve glucose control by stimulating insulin secretion and suppressing glucagon release, both in a glucose-dependent manner. There are two GLP-1R agonists approved for the treatment of T2D: once daily liraglutide and twice daily exenatide, both administered by sc injection. Based on recent clinical trials, GLP-1R agonists suggest having a protective role in cardiovascular risk factors besides improving glycemic control, compared to placebo and to standard diabetes therapies. Both liraglutide and exenatide have demonstrated to induce clinically significant weight loss and to reduce systolic blood pressure. Liraglutide also has a positive effect on the lipid profile and cardiovascular risk biomakers. Furthermore, recent data shows a direct effect of GLP-1 and its metabolites in the vascular endothelium and the myocardium, leading to vasodilator effects and improved cardiac function in humans with acute myocardial infarction or congestive heart failure. GLP-1R agonists have a positive impact on cardiovascular risk factors otherwise not addressed by most standard diabetes therapies. Whether these new compounds actually decrease cardiovascular disease and mortality remains to be demonstrated in outcome studies.

Most trials on the effect of exercise on patients with diabetes mellitus focused on their glycaemic control, only a few focused on sexual dysfunction. A comprehensive two-decade literature review (1989-2009) from peer-reviewed journals was undertaken to examine the roles if any, of therapeutic exercise as an intervention for sexual dysfunction in patients with diabetes. Because of the paucity of studies on this subject, meta-analyses, small and non-randomized trials cited on Medline, Pedro, Embase, Scirus, Highwire and the Cochrane Library of systematic reviews were examined. Sexual dysfunction in general, links between diabetes and sexual dysfunction and management options for sexual dysfunction including therapeutic exercises were reviewed. In women, diabetes is reported to slightly increase the risk of decreased sexual arousal, inadequate lubrication and pain on sexual intercourse, while erectile dysfunction is the most common presentation of sexual dysfunction in men. The literature is scanty but shows some effectiveness of therapeutic exercise in managing sexual dysfunction in patients with diabetes. However, this review shows that i) pelvic floor exercises ii) biofeedback techniques iii) electrical stimulation and iv) vaginal dilators are effective in managing sexual dysfunction secondary to other disease factors in the non-diabetic populations. More research is recommended to further establish the efficacy of therapeutic exercises in managing sexual dysfunction in patients with diabetes.

Diabetic retinopathy is a major complication of patients with diabetes mellitus and can lead to a decrease in vision. The precise mechanisms leading to the development of diabetic retinopathy and the progressive decrease of vision are still undetermined. Recent studies have shown that not only vascular but also neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. Because neuronal cell death leads to an irreversible decrease in visual function, early changes in the morphology and physiology of the neural retinas of diabetic patients are important. The alterations of the morphology of the retina can be obtained by high-resolution B-scan optical coherence tomography (OCT). The thickness of the macular area and retinal nerve fiber layer can be measured reliably and accurately by the installed software of OCT instruments. The high-resolution images can be used to evaluate diabetic macular edema and optic nerve damage quantitatively in patients with diabetic retinopathy. This review describes how the OCT measurements can be used to manage patients with diabetic retinopathy. We also present the early retinal changes involved in the pathogenesis of diabetic retinopathy.

Metabolic syndrome, a “cluster” of metabolic disorders including hypertension, increases the cardiovascular risk, and insulin resistance plays a key role in its pathogenesis. In this syndrome antihypertensive treatment with betablockers is underused because of their adverse metabolic effects. The aim was to review the evidences supporting the reasons for under-using beta-blockers in hypertensive patients with metabolic syndrome. A review of Literature has been carried out via PubMed from 1998 to 2008: most of beta-blockers have adverse effects on insulin sensitivity, carbohydrate and lipid metabolism, and are not recommended in metabolic syndrome. However, some recent large studies have shown a better metabolic profile with newer third generation vasodilating beta-blockers, such as Carvedilol and Nebivolol. Vasodilating action of Carvedilol and Nebivolol, due respectively to alpha1-blocking effect and release of nitric oxide, explains the lack of adverse metabolic effects of these beta-blockers that could also be used in hypertensive patients with metabolic syndrome.

Purpose: Diabetic patients with co-morbid mental illness are commonly encountered in clinical practice. Not only are diabetes and mental illness both common in the general population, but rates of diabetes are significantly higher in individuals with psychiatric disorders. This paper reviews literature related to the interplay between these pathologies and the consequent clinical challenge faced by physicians. Methods: A systematic review was conducted, examining specific aspects of psychiatric illness which may affect diabetic outcomes. Results: Decreased adherence is a feature of many psychiatric conditions, and can have a major effect on diabetic management and development of long term complications. Glycemic regulation may also be complicated by physiologic changes affecting carbohydrate metabolism. Patterns of counter-regulatory hormone secretion are altered in many psychiatric conditions, which may necessitate an altered diabetic treatment regimen. Further difficulties arise as many psychiatric medications have adverse metabolic effects. Conclusions: Diabetic patients with mental illness present a unique clinical challenge as a result of issues related to behaviour, physiology and medications. Clinicians should be able to recognize “problem patients” who may in fact have undiagnosed, treatable, psychiatric pathology. In patients carrying existing diagnoses, complicating factors to diabetic control should be recognized, and steps taken to minimize adverse effects.

Ghrelin is an orexigenic peptide hormone secreted into the systemic circulation predominantly by the X/A-like cells in the mucosa of the stomach. In addiction to central effects on food intake and growth hormone release, ghrelin has also important vascular and metabolic actions. Our laboratory has shown that administration of exogenous ghrelin acutely improves endothelial function by increasing nitric oxide bioavailability and normalizing the alterate balance between endothelin 1/nitric oxide (ET-1/NO) within the vasculature of individuals with metabolic syndrome. Additionally, in endothelial cell cultures, it has been shown that ghrelin directly stimulates NO production using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Other cardiovascular effects of ghrelin include lowering of peripheral resistance, improvement of contractility and cardiac output. In addition ghrelin plays a significant role in the regulation of glucose homeostasis, lipid profiles and body composition. Importantly, ghrelin has antiinflammatory and antiapoptotic effects both in vivo and in vitro. This review focuses on the physiological roles of ghrelin in regulating metabolic and endothelial function and on the potential of ghrelin as the therapeutic target to treat metabolic and cardiovascular disorders.

Diabetes mellitus is an increasingly common disease that affects people of all ages, resulting in significant morbidity and mortality. Diabetic patients require more frequent hospitalization, have greater lengths of stay, and cost more to manage than non-diabetics. The major risk factors for diabetics undergoing surgery are the end-organ diseases associated with diabetes: cardiovascular disease, autonomic neuropathy and immune deficiency. Physicians should pay extra attention to preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal perioperative management. Furthermore, these patients unexpectedly develop hemodynamic instability in response to vasopressor or vasodilator administration during anesthesia, this being of particular importance in patients with concurrent ischemic heart disease in whom it may have a direct effect on mortality. Recent studies have shown that tight glycemic control in diabetic patients undergoing major surgery has been shown to improve perioperative morbidity and mortality.

The aim of this study is to collate all available data on antidiabetic plants that inhibit alpha glucosidase, reported mainly by Medline (PubMed) these last years. In the present study, interest is focused on experimental researches conducted on hypoglycemic plants particularly those which show alpha glucosidase inhibitor activity alongside bioactive components. This study describes 47 species that belong to 29 families. The plant families, which enclose the species, studied most as inhibitors of alphaglucosidase, are Fabaceae (6 species), Crassulaceae (3 species), Hippocrateacaea (3 species), Lamiaceae (3 sp.), and Myrtaceae (3 species), with most studied species being Salacia reticulata (Hippocrateaceae) and Morus alba (Moraceae). The study also covers natural products (active natural components and crude extracts) isolated from the medicinal plants which inhibit alpha glucosidase as reported this last decade. Many kinds of these isolated natural products show strong activity such as, Alkaloids, stilbenoids (polyphenol), triterpene, acids (chlorogenic acid, betulinic acid, syringic acid, vanillic acid, bartogenic acid, oleanolic acid, dehydrotrametenolic acid, corosolic acid, ellagic acid, ursolic acid, gallic acid), phytosterol, myoinositol, flavonoids, Flavonolignans, anthraquinones, anthrones, and xanthones, Feruloylglucosides, flavanone glucosides, acetophenone glucosides, glucopyranoside derivatives, genine derivatives, flavonol, anthocyanin and others.

It is likely that the heritability of T2DM goes beyond simple genetic markers and involves epigenetic mechanisms. Neel's Thrifty Gene Hypothesis was expanded by Chakravarthy to include metabolic cycling and the dissonance between our stone-age genes with a space-age lifestyle. Further modifications of this hypothesis continued after recent developments in evolutionary and epigenetic research. At the molecular forefront, energy-sensing signaling pathways in T2DM, such as PGC1α, AMPK, O-GlcNAc and most recently SIRT1 have been shown to play key roles in oxidative stress, mitochondrial dysfunction, inflammation and glucolipotoxicity, which are the hallmarks of insulin resistance and T2DM, Furthermore, SIRT1, PGC1α and O-GlcNAc also regulate gene expression and may play a role in the epigenetic machinery, thus providing an explanation to how metabolism switches to either a 'thrift' or 'spend' mode depending on food availability. Separate evidence on adaptations to exercise further links T2DM with decreased physical activity. In this review, the major findings from the epigenetic, epidemiological, molecular and clinical forefronts are integrated and unified as a coherent hypothesis for the etiology and pathogenesis of T2DM. It is an opportune time to start connecting the dots to provide the much needed basis for a better understanding of T2DM and a more targeted approach to drug development and treatment strategies.