Current Diabetes Reviews - Volume 5, Issue 2, 2009

Diabetes, characterized by chronic hyperglycemia, has reached serious epidemic proportions. It is also not infrequent to find increased incidence of liver injury in diabetics and hyperglycemia plays an important role in promoting liver injury through several mechanisms. The following review identifies the pathways through which hyperglycemia causes changes in liver of various animal models and liver cell culture models, and elucidates the mechanisms and consequences of hyperglycemia induced liver injury in humans. Some of the pathways which are hyperglycemia driven include increased oxidative and nitrosative stress, activation of stress signaling pathways and increased cytokine levels, impairment of protective mechanisms such as the expression of molecular chaperones and proteosome activity, and dysregulation of glucose and lipid metabolism. Thus, hyperglycemia induced changes in the liver's cellular environment in in vitro and in vivo models have been documented extensively in the literature.

Development of therapeutic measures to reduce the risk of potentially fatal episodes of hypoglycaemia and thus to achieve the full benefits of intensive insulin therapy in diabetic patients requires a complete understanding of the multifactorial mechanisms for repeated hypoglycaemia-induced blunting of the sympatho-adrenal response (BSAR). After critical analysis of the hypotheses, this review paper suggests a heuristic theory. This theory suggests two mechanisms for the BSAR, each involving a critical role for the central brain noradrenergic system. Furthermore, this theory also suggests that the lateral hypothalamus (LH) plays an important role in this phenomenon. Within the framework of this theory, explanations for 1) sexual dimorphism in the adrenomedullary response (AR), 2) dissociation in the blunting of the AR and the sympathetic response (SR) and 3) antecedent exercise-induced blunting of the AR are provided. In addition, habituation of orexin-A neurons is suggested to cause defective awakening. Moreover, potential therapeutics measures have been also suggested that will reduce or prevent severe episodes of hypoglycaemia.

Glucagon-like peptide-1 (GLP-1) is a gut hormone that plays an important role in regulating glucose homeostasis by both its pancreatic and extrapancreatic activity. Defects of GLP-1 characterize type 2 diabetes as a primary or perhaps consequent phenomenon, resulting in inappropriately low insulin secretion after oral ingestion of nutrients. The discovery that cleavage by the ubiquitous enzyme dipeptidyl peptidase-IV (DPP-IV) is the primary route of GLP-1 metabolism formed the rationale behind the proposal to prevent degradation of endogenously released GLP-1 by DPP-IV inhibition as a novel approach to the management of type 2 diabetes. Enhanced insulin secretion as well as delayed gastric emptying, reduced glucagon secretion, and inhibited apoptosis of beta cells resulting from blockade of incretin degradation, have been proposed as the major actions of DPP-IV inhibitors as antidiabetic agents. Clinical studies to date indicate that DPP-IV inhibitors effectively ameliorate islet dysfunction and improve glucose control in patients with type 2 diabetes. They appear to have excellent therapeutic effectiveness as monotherapy in patients inadequately controlled with diet and exercise and as add-on therapy in combination with metformin, thiazolidinediones, and insulin. Their pharmacokinetic and pharmacodynamic profiles support once-daily dosing, with relatively few adverse effects.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, resistance to insulin action, or a combination of both. DM has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes is anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for treatment of diabetes are required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the anti diabetic activity over past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 100 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to diabetes.

Diabetes patients are known to have a worse quality of life than individuals without diabetes. They also have an increased risk for depressive symptoms, which may have an additional negative effect on their quality of life. This systematic review summarizes the current knowledge on the association between depressive symptoms and quality of life in individuals with diabetes. A systematic literature search using MEDLINE, Psychinfo, Social SciSearch, SciSearch and EMBASE was conducted from January 1990 until September 2007. We identified studies that compared quality of life between diabetic individuals with and without depressive symptoms. Twenty studies were identified, including eighteen cross-sectional and two longitudinal studies. Quality of life was measured as generic, diabetes specific and domain specific quality of life. All studies reported a negative association between depressive symptoms and at least one aspect of quality of life in people with diabetes. Diabetic individuals with depressive symptoms also had a severely lower diabetes specific quality of life. Generic and domain specific quality of life were found to be mild to moderately lower in the presence of depressive symptoms. Therefore, increased awareness and monitoring for depression is needed within different diabetes care settings.

The role of altered mitochondria function has recently emerged as an important mechanism for the development of diabetic complications. Altered mitochondria function has also been implicated in the ageing process, defective insulin secretion, hypertension, arteriosclerosis, ischemia-reperfusion injury and apoptosis. Normally, the mitochondria are associated with ATP production using primarily pyruvate as the substrate, but recent reports indicate that tissue specific preferences exist. Also, the mitochondria are a substantial source of superoxide production, preferentially during states of elevated intracellular glucose concentrations. The mitochondria function is regulated by several factors including nitric oxide, oxidative stress, mammalian target of rapamycin, ADP and Pi availability, which result in a complex regulation of ATP production and oxygen consumption, but also superoxide generation. These factors seem to be tissue specific, which warrants a more diverse mechanistic model applying to that specific tissue or cell type. This review presents the basic functions of the mitochondria and focuses on the complex interplay between oxidative stress, nitric oxide and uncoupling proteins in regulating mitochondria function with special focus on diabetes-induced alterations occurring on the mitochondria level.

We review the mechanisms leading to hyperglycaemic damage and draw functional extrapolations aiming to an improved management of surgical complications, which are common among diabetic patients.