Current Diabetes Reviews - Volume 7, Issue 6, 2011

MicroRNAs ( miRNAs) are highly conserved, 19-23 nucleotide long, non-coding, endogenous RNA, which are transcribed from either intergenic, intronic or polycistronic regions and modulate gene expression through mRNA degradation or translational repression. They are fine tuners of biological processes and have recently emerged as biomarkers and therapeutic targets of cardiovascular diseases. Several miRNAs regulate stem cell for differentiation, proliferation and degeneration. Stem cells are pluripotent, self-renewing and clonogenic cells having tremendous potential for regenerative therapy. The current therapeutic approach is unable to cope up with rapidly increasing rates of diabetes and cardiovascular diseases. The empirical and clinical evidences revealed that transplantation of exogenous stem cells can regenerate beta cells in diabetic patients and myocardium in patients with myocardial infarction. Nevertheless, the major limitation of stem cell therapy is unpredictable behavior of exogenous stem cells that incur few reports of teratoma and cancer after transplantation. Therefore, understanding the regulation of newly transplanted stem cells into the foreign body is a major challenge to translational research / clinical trail. Since miRNA plays pivotal role in the fine regulation of proliferation and differentiation of stem cells, investigations on the regulation of miRNA in transplanted stem cells in a specific micro-environment that houses the stem cell is indispensable. Additionally, the inhibition or over expression of specific miRNAs in the niche surrounding the stem cell will be crucial for maintaining the specific lineage of exogenous stem cells. This review embodies major advancement in the field of miRNA biogenesis and its regulatory mechanisms, role of different miRNAs and stem cells as a therapeutic target for diabetes and cardiovascular diseases. It also provides insights into the novel future therapy, where synergistic approach for manipulating miRNAs and stem cells will emerged as a potential treatment for diabetes and cardiovascular diseases.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that involves menstrual dysfunction and reproductive difficulty as well as metabolic problems. From a genetic point of view, it is a complex disease that is subject to environmental influences, mainly dietary, which makes it similar to other metabolic processes, such as diabetes and obesity. So, the interest of the diagnosis of the PCOS is, not only to improve fertility but to prevent possible future medical complications like the diabetes mellitus and the obesity. Due to the classical definition of PCOS as functional hyperandrogenism, the race to discover genetic alterations that could lead to the development of PCOS started with the androgen metabolism genes. However, the list of candidates was later expanded to other genes outside this hormonal pathway, and it now includes genes involved in carbohydrate and lipid metabolism as well as those involved in inflammatory processes. Synopsis: The list of genes candidates involved in PCOS is related to diabetes and inflammatory processes.

While lifestyle modifications and metformin are the cornerstone of the initial management of type 2 diabetes mellitus, there is an increasing array of second and third-line pharmacological agents for this condition. These include sulphonylureas, insulin, thiazolidinediones and alpha-glucosidase inhibitors, with the more recent addition of glucagon- like peptide-1 agonists, dipeptidyl peptidase-IV inhibitors and pramlintide. Moreover, insulin analogues that better simulate endogenous insulin secretion have been developed. This review aims to provide an update on the current pharmacological management of type 2 diabetes mellitus, and to highlight the benefits and limitations of each treatment.

The amount of research and technology related to diabetes mellitus has grown dramatically over the past few decades. This knowledge has led to many advances in the detection and treatment of prediabetes and diabetes and the prevention of their related complications. However, there continues to be a distinct gap between these advances and the medical care of patients with diabetes. This article focuses on translational research findings that address the causes of this gap and that attempt to find methods to close this gap at the level of the provider, healthcare system, and patient. The research findings are discussed in terms of elements of the chronic care model originally proposed by Wagner et al. to help optimize the care of patients with any chronic disease such as diabetes.

Impaired diabetic wound healing (WH) constitutes a serious diabetic complication with increased morbidity, mortality and health expenditure. The exact pathogenetic mechanisms have not been fully clarified. A variety of hyperglycemia and oxidative stress related factors, have been proposed, including advanced glycaction end products (AGE). The existing literature data, support the role of AGE in the pathogenesis of diabetic complications, namely micro- and macro- angiopathy which underlie delayed diabetic WH. In addition, a large body of evidence support a direct negative effect of AGE in the WH process by their interference with various components involved in the cascade following skin injury. Endogenously formed or exogenously derived AGE, in a similar manner, affect negatively the WH process in diabetes. It is obvious that further studies are needed to clarify the exact role of AGE in the impaired diabetic WH and offer possible new therapeutic strategies

Since the first in-vitro fertilisation (IVF) birth in 1978, the number of children born by assisted reproductive technologies (ART) continues to increase worldwide. However, the safety issues surrounding these procedures remain controversial, and the long term impact on human health is unknown. There is emerging evidence to indicate that IVF may predispose individuals to increased incidence of obesity, elevated blood pressure, fasting glucose and triglycerides and subclinical hypothyroidism. However, few studies have been conducted to date and the underlying mechanisms are unclear. This review will summarize the existing evidence in animal models and in humans, and will discuss epigenetic alterations, which may link manipulation of the pre-implantation embryo with increased risk of the later development of obesity, insulin resistance, type 2 diabetes and cardiovascular disease in offspring. Since these diseases are the leading cause of mortality and can be delayed or prevented by lifestyle modification, prospective follow up studies in IVF born adults are now urgently required to determine the degree of risks utilizing gold standard measures in human and animal models.

The association between diabetes and periodontal diseases is well-established. Diabetes is a risk factor for periodontal disease, with diabetic patients exhibiting an increased prevalence, extent and severity of gingivitis and perio- dontitis compared to healthy adults. Several mechanisms involved in the pathogenesis of diabetes have also been associated with periodontal disease progression. It is recognized today that there is a bidirectional relationship between diabetes and periodontal disease, with recent research showing that periodontal disease may affect the metabolic control of diabetes in diabetic patients. In this review, we present the current knowledge of the interplay between periodontal diseases and diabetes through the evaluation of randomized control and longitudinal cohort studies published in the past 15 years. Current data support the conclusion that diabetic patients are at increased risk for periodontal diseases, and that patients with poorly controlled diabetes are at risk for severe periodontitis. This results in the destruction of oral connective tissue and generalized bone loss, leading ultimately to tooth loss. Although the effect of periodontal disease on glycemic control in type 1 diabetic patients is controversial, evidence does show a direct correlation between periodontal health and glycemic control in type 2 diabetic patients. Furthermore, several studies have demonstrated the beneficial effect of periodontal treatment on metabolic control of type 2 diabetic patients.