Current Diabetes Reviews - Volume 8, Issue 1, 2012

Current Diabetes Reviews is now entering its 8th year of publication. It has become well established in the field, publishing high quality review articles on clinical and basic research in the subject area of diabetes mellitus. The journal will continue to have a broad base, publishing reviews on the latest advances in diabetes and its complications, including the underlying physiology, pharmacology, pathogenesis, epidemiology, clinical care and therapeutic strategies. To this end I invite notable clinicians and scientists to contribute general articles and guest edited hot topics in their respective areas of interest. I would like to thank the Editorial Board Members for their efforts and enthusiasm, as well as the Guest Editors, reviewers and last but not least, the authors for their excellent contributions.

In the last few decades, the prevalence of overweight and essential obesity has been undergoing a fast and progressive worldwide increase. Obesity has been in turn linked to type II diabetes, with the total number of diabetic patients worryingly increasing, in the last fifteen years, suggesting a pandemic phenomenon. At the same time, an increase in the prevalence of cardiovascular diseases has been also recorded. Increasing evidence suggests that the diet is involved in such escalation. In particular, the progressive globalization of food industry allowed massive supply, at a relatively low price, of a great variety of pre-packed food and bakery products, with very high energy content. Most of this food contains high amounts of saturated fatty acids (SFA) and of hydrogenated or trans fatty acids (TFA), that probably represent the prominent risk factors in the diet. Herein we will report diffusion and possible impact on health of such molecules, with reference to coronary heart disease, insulin resistance, metabolic syndrome and diabetes. We will also discuss the cellular and molecular mechanisms of action of fatty acids and fatty acid-derivatives which have been involved either in promoting or in preventing human pathologies. Free fatty acids (FFA) are not indeed only essential fuels for the organism. They also act as ligands for both membrane and nuclear receptors involved in different signaling pathways. Notably, some of these pathways can induce cell stress and apoptosis. Most important, FFA can affect glucose-induced insulin secretion and activate β-cell death. These events can be at least in part counteracted by polyunsaturated fatty acids.

Vitamin D plays a role in a range of functions that may impact on glycaemic control. In this study we systematically report on clinical studies evaluating the impact of vitamin D on aspects of hyperglycaemia in non-pregnant adults. A total of 1,294 articles, of which 417 were reviews, were identified. No well-designed randomised, controlled trials were identified that specifically investigated the effects of vitamin D supplementation on glucose and insulin concentrations. The majority of the studies that are available were poorly designed, having limited numbers, short study duration, or were conducted in volunteers with normal baseline, as measured by 25-hydroxyvitamin D (25(OH)D), concentrations or used inadequate doses of the supplements to normalise vitamin D concentrations, or used inappropriate analyses. Most studies did not observe improvements in glycaemia, with few exceptions. The results were more equivocal for aspects of insulin resistance. Most found no benefit on measures of insulin resistance, although some did. However, more studies described improved insulin release, although data from the studies to date are really inadequate to provide any reliable conclusions. Well-conducted randomised, controlled trials with adequate vitamin D doses are required to effectively assess whether this vitamin can reduce the incidence of diabetes.

Diabetes mellitus has become a major health concern worldwide and its incidence is projected to increase. Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are considered the most sight-threatening ocular complications in these patients. Pivotal studies, such as the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetic Retinopathy Study (DRS), have established macular and pan-retinal laser as the gold-standard of treatment for these complications. The recent discovery of the vascular endothelial growth factor (VEGF) and its role in the development of proliferative disease, has led to a movement towards treating PDR and DME with anti-angiogenic medications alone or in conjunction with the gold-standard of care. Due to the severity of the diabetic ocular complications and the rising incidence of diabetes worldwide, it is important for the non-ophthalmologist care provider to be informed of the new treatments available for these conditions in an effort to better guide their patients. In this review, I will discuss the importance of these new methods of treatment as well as the significance of systemic glucose control, vitreous surgery and laser photocoagulation.

The secosteroid vitamin D is best known for its role in calcium regulation and bone metabolism. Recently, however, an emerging body of evidence has suggested that vitamin D may have previously-unrecognized effects on a variety of physiologic processes, including those relating to glucose homeostasis. Indeed, vitamin D insufficiency has been linked with type 2 diabetes (T2DM). In this review, the potential association between vitamin D and T2DM will be evaluated from both a pathophysiologic and clinical perspective. We consider the biologic evidence in support of a mechanistic contribution of vitamin D insufficiency to insulin resistance and beta-cell dysfunction, the two main pathophysiologic defects underlying T2DM. We also evaluate the clinical data linking vitamin D with these metabolic defects and dysglycemia. Finally, interventional studies addressing the effect of vitamin D supplementation on glucose homeostasis are considered. At present, this evolving literature is marked by many conflicting results and methodologic limitations, such that definitive conclusion on the role of vitamin D in T2DM remains elusive. Nevertheless, in light of the widespread prevalence of both vitamin D insufficiency and T2DM, this potential relationship could hold enormous public health implications and hence demands further study to address its unresolved questions.

Diabetes mellitus (DM) is a very common disease which, if a good glycemic control is not achieved, can lead to serious chronic complications such as cardiovascular disease, retinopathy, nephropathy and neuropathy. Selfmonitoring of blood glucose is a fundamental tool for the proper adjustment of the treatment of diabetes and, at present, it is based mainly on capillary blood obtained by finger-prick (the classical glucometers). Since this method is painful and the strips are expensive, investigators have been attracted by the idea of using a non-invasive device for determining blood glucose which would permit more frequent testing and a tighter control of diabetes. The non-invasive measurement of blood glucose is based on the ability of the glucose molecule to interact with various chemical or physical methods. Nevetheless, in spite of some encouraging results and the efforts made over the past 30-40 years, there is no device available at present for use in clinical practice. A possible explanation might be the combination between the specific features of each method and the specific characteristics of diabetic patients, which make them respond differently to physical and chemical methods when compared to their healthy counterparts. In this paper we will give an overview of the noninvasive devices tested so far and their implications for the clinical management of the diabetic patient.

It is now well accepted that early life events can contribute substantially to the likelihood of an individual becoming obese, although many of the mechanisms for this are not well understood. Maternal over- and under-nutrition as well as the postnatal nutritional environment can contribute significantly to obesity throughout life. This review will provide an overview of early life events associated with neuroendocrine programming of obesity and metabolic dysfunction. In particular this review will focus on the long-term impact of perinatal nutrition, as well as the perinatal role of leptin, insulin, and glucocorticoids in programming the hypothalamic circuitry responsible for appropriate regulation of feeding and metabolism throughout life.

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the pathogenesis of T2D. This review focuses on mechanisms whereby reactive oxygen species (ROS) produced by β-cell in response to metabolic stress affect mitochondrial structure and function and lead to β-cell failure. Specifically, ROS oxidize mitochondrial membrane phospholipids such as cardiolipin, which impairs membrane integrity and leads to cytochrome c release and apoptosis. In addition, ROS activate UCP2 via peroxidation of the mitochondrial membrane phospholipids, which results in proton leak leading to reduced ATP synthesis and content in β-cells - critical parameters in the regulation of glucose-stimulated insulin secretion. Group VIA Phospholipase A2 (iPLA2β) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to development of T2D. Interventions that attenuate the adverse effects of ROS on β-cell mitochondrial phospholipids may prevent or retard the development of T2D.