Current Diabetes Reviews - Volume 5, Issue 4, 2009

The mechanism of dead-in-bed syndrome (DBS), a rare but devastating condition that mainly affects young type 1 diabetes patients, remains mysterious. A new theory is proposed to explain this syndrome. This theory suggests that repeated episodes of hypoglycaemia-induced adaptation in orexin-A neurons cause (i) defective awakening and (ii) hypotonia of upper airway muscles during sleep. Consequently, due to the combined effect of these factors, long-term exposure of intermittent hypoxia occurs, leading to a combination of factors - such as depression of ventilation, increase in sympathetic tone, fluctuations in intrathoracic pressure and cardiac arrhythmias - these in conjunction with an underlying cardiovascular pathology (genetically inherited or acquired) cause cardio-respiratory failure and thus sudden death during sleep. This mechanism can be generalized to explain other cases of sudden unexplained nocturnal deaths including sudden infant deaths (SIDs).

FGF21 is a novel member of the FGFs family, is mainly expressed in liver and it functions as a potent activator of glucose uptake on adipocytes. When over expressed in transgenic mice, it protects animals from diet-induced obesity and its administration to diabetic rodents and monkeys lowers blood glucose and triglyceride levels. Recently, increased levels of FGF21 have been identified as an independent risk factor related with metabolic syndrome. A review of the relevant roles of FGF21 in metabolism is presented here.

The prevalence of Type 2 diabetes, a disease difficult to treat and expensive to manage, is increasing rapidly worldwide. It is also known that lifestyle, and particularly dietary habits, play an important role in the development of diabetes. Adherence to a healthy dietary pattern, like the Mediterranean diet, exerts a beneficial role regarding the development of diabetes. Additionally certain individual food groups and components of the diet, such as monounsaturated fatty acids, fruits, vegetables, whole grain cereals, dietary fiber, fish, and moderate consumption of alcohol, also may protect against the development of diabetes, possibly through the amelioration of insulin sensitivity and their antiinflammatory actions. Unfortunately, dietary habits in the developed world are changing towards an unhealthier direction. Consequently, emphasis should be given on encouraging at population and individual level for adopting a healthier lifestyle, including dietary habits, in order to prevent the development of Type 2 diabetes.

The prevalence of obesity and its associated disorders [e.g., insulin resistance, type 2 diabetes and cardiovascular disease (CVD)] has seen a rapid increase in recent years. As such, understanding the mechanisms underlying dietinduced insulin resistance has been a topic of interest. In line with this notion, postprandial oxidative stress has received considerable attention over the past several years due to its involvement in the etiology of the above mentioned conditions. In fact, postprandial oxidative stress has been suggested to be the unifying mechanism in the connection between insulin resistance, Type 2 diabetes and CVD. In addition to this growing association, recent data are now available suggesting a causal role for such prooxidant stress in the development of insulin resistance. This review is intended to provide an overview of literature pertaining to the role of free radical production following feeding, as related to the development of insulin resistance, Type 2 diabetes and CVD.

It has long been recognized that the diagnosis of gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing Type 2 diabetes (T2DM) in the future. In recent years, however, a series of studies have revealed that antepartum glucose tolerance screening, a standard element of current obstetrical care instituted for the purpose of detecting GDM, may provide previously-unrecognized insight into a woman's future risk of metabolic and vascular disease. Indeed, it has emerged that in fact any degree of abnormal glucose tolerance detected on antepartum screening (i.e. not just GDM) predicts an increased future risk of pre-diabetes and diabetes, one that is proportional to the severity of dysglycemia observed in pregnancy. In addition, in the years following the index pregnancy, women with a history of GDM exhibit an enhanced cardiovascular risk profile and ultimately an increased incidence of cardiovascular disease (CVD), risks that may similarly extend to women with milder gestational glucose intolerance as well. Thus, by providing a unique window to a woman's risk potential for future metabolic and vascular disease, glucose tolerance testing in pregnancy, as currently practiced, may offer an opportunity for the early identification of high-risk individuals prior to the onset of clinical disease. Ultimately, the insight so derived may inform strategies for postpartum surveillance, risk factor modification, and disease prevention that may eventually lead to a reduction in the burden of T2DM and CVD in women.

Type 2 diabetes mellitus increases the risk of cerebro/cardiovascular events, since this disease leads to the development of premature atherosclerosis and atherothrombosis associated with diabetes accelerates diabetic macroangiopathy. Microparticles (MPs) released from cells (MPs) may play a role in the normal hemostatic response to vascular injury and a role in clinical diseases because they express phospholipids, which function as procoagulants. MPs were first observed as released vesicles from platelets following adhesion to vessel walls. Currently, the number of clinical disorders associated with elevated MPs is increasing. A few studies on the potential role of platelet-derived MPs in diabetic complications can be reported. MPs are elevated in diabetic patients however studies have found differences in the MP profile in relation to disease type and the presence or absence of MPs. Levels of platelet-derived MPs and monocyte-derived MPs have been shown to correlate with diabetic complications or the extent of diabetic retinopathy, which is associated with microvascular damage. Elevated endothelial cell-derived MP levels are predictive for the presence of coronary artery lesions, and it is a more significant independent risk factor than length of diabetic disease, lipid levels or presence of hypertension. Interestingly, elevated endothelial cell-derived MP levels are predictive in identifying a subpopulation of diabetic patients without typical anginal symptoms who have angiographic evidence of coronary artery disease. We will present evidence for a dynamic role of MPs in type 2 diabetes.

All forms of diabetes are increasing in prevalence, but with the advent of the obesity epidemic, we now face the prospect of an increasing number of women conceiving whilst taking traditional oral antidiabetic agents (OADs). This is also further complicated by the availability of new incretin-based therapies, the dipeptidylpeptidase-4 (DPP-IV) inhibitors and glucagon-like-1 receptor (GLP-1R) analogues. Original concerns regarding the use of such OADs have meant that diet control and insulin has been the mainstay of treatment for hyperglycaemia during pregnancy. However, recent NICE guidelines have suggested a role for oral antidiabetic agents. Safety is of paramount concern, especially in pregnancy, and this review will discuss the evidence to date.

The metabolic syndrome consists of obesity, insulin resistance, dyslipidemia, atherosclerosis, and hypertension. Its clinical outcomes are stroke, myocardial infarction, and type 2 diabetes. Each of these is more frequent in African- Americans than in Caucasians. This is surprising since most studies indicate that the incidence of the metabolic syndrome is lower in African-American than Caucasian adults. There is growing evidence that adult cardiovascular disease has its origin in childhood and adolescents. Thus, it is important that we understand differences in the pathophysiological precursors to metabolic and cardiovascular disease in this age group. Many studies, but not all, have demonstrated that African- American children and adolescents are insulin resistant compared to similar age Caucasians. The increased insulin resistance occurs in spite of lower triglyceride levels. Low triglyceride levels are usually associated with increased insulin sensitivity. There is evidence that the relationship between triglycerides and insulin sensitivity differs between the two races. African-Americans compensate for the increased insulin resistance by increasing insulin secretion and insulin clearance. Interestingly, those studies that have not found increased insulin resistance in African-Americans have found increased insulin secretion suggesting the increased secretion may precede the insulin resistance. Hyperinsulinism and insulin resistance are linked to endothelial dysfunction in adults and African-American adolescents have poorer endothelial function than do Caucasians. In African-American adolescents, endothelial function decreases as insulin secretion increases. It is likely that the hyperinsulinism, insulin resistance and endothelial dysfunction in adolescent African-American adolescents play an important role in the increased rates of cardiovascular disease and type 2 diabetes. Future research should focus on the mechanisms of these abnormalities and ways to prevent their development in this age group.

GLP-1 (glucagon-like peptide-1) is a peptide hormone secreted from endocrine cells in the intestinal mucosa in response to meals. The major effects of GLP-1 are to increase glucose-induced insulin secretion and reduce glucagon release, but GLP-1 also inhibits gastric emptying rate and reduces appetite and bodyweight in obese subjects. In vivo studies using animal models of type 2 diabetes and in vitro studies using human islet cells have suggested that GLP-1 or GLP-1 analogues are also able to increase ß-cell mass, but in animal models of type 1 diabetes, there is much less evidence for a ß-cell preserving effect. This review summarizes the present knowledge of GLP-1 and its analogues regarding its role as a possible treatment in patients with type 1 diabetes. The studies that address the effect of GLP-1 and GLP-1 analogues on ß-cell mass in both type 2 and type 1 diabetes, as well as the potential of GLP-1 as an adjuvant therapy in islet cell transplantation, will be reviewed. Suggestions for future studies of GLP-1 treatment in type 1 diabetes may include early treatment in order to preserve ß-cell mass and prolong the remission period, but should also take a potential insulin sparing effect and changes in the risk of hypoglycemia into account.