Current Diabetes Reviews - Volume 3, Issue 2, 2007

Progression of diabetic retinopathy (DR) occurs at least temporarily during pregnancy and postpartum. The pathogenetic mechanisms of DR progression during pregnancy are not fully understood. Several factors related to metabolic changes (hyperglycaemia), diabetes itself (duration of diabetes before conception, baseline status of DR), pregnancy physiology (hypervolaemia and hypercoagulation, impaired retinal autoregulation) and pregnancy complications (pre-eclampsia) seem to play important roles in the progression of DR during pregnancy. On the other hand, systemic angiopoietic and vasoactive factors seem to have minor role in the deterioration of DR during that time period. Good glycaemic control, normotension, lack of nephropathy as well as lack of pre-proliferative/proliferative changes of DR are good prognostic factors as regards the progression of DR during pregnancy. However, pregnancy seems to have no long-term detrimental effects as regards the progression of DR unless it has proceeded to pre-proliferative and proliferative phases.

Type 2 Diabetes Mellitus (T2DM) is a disease of over nutrition; the onset and progression of which, is associated with excess fat accumulation in the abdomen, muscles and liver. In this review, we focus on management of obesity as the primary strategy for management of disorders of glucose metabolism. Modest weight loss (∼7%) achieved by diet and exercise can prevent, or delay, the onset of T2DM. In those with established T2DM, weight loss reduces fasting and post-prandial plasma glucose levels, HbA1c, and the need for pharmacotherapy. The beneficial effects on glucose metabolism of caloric restriction, and aerobic and resistance exercise, may occur independently of weight loss. When substantial weight loss is required, meal replacements allow a large reduction in energy consumption whilst maintaining micronutrient intake. Pharmacotherapy for obesity, as part of an integrated management plan, is useful for maintaining weight loss and optimising glycaemic control. The most effective long-term therapy for obesity remains bariatric surgery, which is associated with resolution of T2DM in over 80% of patients. The currently available pharmacotherapies for T2DM mostly result in weight gain. Pramlintide and exenatide are new therapies which hold promise, because in addition to improved glycaemic control, they also result in weight loss.

Type 2 diabetes is associated with an increased incidence of coronary heart disease and cardiovascular complications. One crucial step in the initiation and progression of atherosclerosis is the unregulated uptake of oxidized low-density lipoprotein (oxLDL) by vascular wall components through scavenger receptors. Identification of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as the major receptor for oxLDL in endothelial cells has provided a new clue to the mechanisms involved in oxLDL accumulation in the vessel wall. This receptor, by facilitating the uptake of oxLDL, induces endothelial dysfunction and mediates numerous oxLDL-induced proatherogenic effects. Besides endothelial cells, LOX-1 is also expressed by smooth muscle cells and macrophages. In these cells, LOX- 1 may function as a scavenger receptor and promote foam cell formation. Notably, LOX-1 is induced by multiple stimuli relevant to atherogenesis and inflammation and is up-regulated in various proatherogenic conditions, including diabetes. As such, activation of vascular cells by oxLDL through LOX-1 may be relevant to the development and progression of human diabetic vasculopathy. This review summarizes recent advances related to the role of LOX-1 in atherosclerosis, its regulation by metabolic and inflammatory factors relevant to diabetes and the impact of these factors on LOX-1-mediated proatherogenic events linked to diabetic vasculopathy.

The dissection of mechanisms that regulate glucose transport by insulin has revealed an intricate network of signaling molecules scattered from the insulin receptor to the intracellular glucose transporter GLUT4. It is also appreciated that some insulin receptor signals jaunt in different directions to regulate events essential for the efficient redistribution of GLUT4 to the plasma membrane. Moreover key assists in the process appear to be arranged by membrane lipids and cytoskeletal proteins. Following current considerations of insulin signals regulating GLUT4, this review will focus on in vitro and in vivo evidence that supports an essential role for phosphoinositides and actin filaments in the control of glucose transport. The discussion will visit recent cell culture, whole animal, and human data highlighting membrane and cytoskeletal aspects of insulin resistance.

Purpose of review: The mortality of type 2 diabetic patients with renal disease is high during both the pre-dialysis period as well as the period under dialysis therapy. With respect to rare data in the literature it may be assumed that the mortality rate is especially high during the last year before and the first year after start of dialysis therapy. Recent findings: After reviewing the reports in the literature dealing with survival of diabetic patients with nephropathy it may be concluded that mortality is especially high during the year before and after initiating dialysis. There are exact survival data of type 2 diabetic patients under dialysis therapy but only few data concerning the survival during the last year prior to dialysis treatment. The possible reasons for this higher mortality shortly before and after start of dialysis are discussed in this article. Summary: The mortality in type 2 diabetic patients is especially high during the last year before and the first year after the start of dialysis therapy. However, only the higher mortality during the first year after initiating dialysis is well documented in the literature. Those patients who die early within 90 days of dialysis are not registered in the registries, therefore, the overall mortality during the first dialysis year is at least 5% higher than the registered. uring both periods several factors may play a causal role in the high mortality, a higher prevalence of heart failure, and a progression of macroangiopathy with higher incidence of cardiovascular events due to traditional and non-traditional risk factors, especially inflammation and oxidative stress.

Objective - To assess the comparative efficacy and safety of pioglitazone and rosiglitazone. Research design and methods - Multiple electronic databases were searched for randomized, controlled trials (RCTs) of efficacy or effectiveness and for studies of any design which reported adverse events. Pooled estimates were calculated using a random effects model. Results - Eighty-seven RCTs fulfilled our inclusion criteria for efficacy or effectiveness and 42 studies examined safety or tolerability. Two head-to-head RCTs of type 2 diabetes demonstrated significant improvements in A1c in both groups at follow-up with no significant difference between groups; a third study found no significant change in A1c in either group. The pooled estimate of effect on A1c for pioglitazone compared to placebo was -0.99% (95% confidence interval [CI], -1.18, -0.81) and for rosiglitazone was -0.92% (95% CI, - 1.2, -0.64). Indirect comparison revealed no significant difference in A1c (between-drug difference -0.07% [95% CI, -0.41, 0.27]). Rosiglitazone increased total cholesterol compared to pioglitazone (net between-drug effect 13.91 mg/dl [95% CI, 1.20 to 26.62]). Both drugs increased weight by 2 to 3 kg and rates of adverse events were similar for the two drugs. Data were insufficient to assess comparative effects on health outcomes such as cardiovascular events. Conclusions - Based largely on indirect evidence, the two thiazolidinediones appear to have similar effects on glycemic control and similar side-effect profiles. Rosiglitazone may increase total cholesterol compared to pioglitazone. Studies are needed which provide direct comparisons between the two drugs, particularly for long-term health outcomes.

The severity of the type 2 diabetes epidemic is widely acknowledged. Demographic, social, and cultural changes around the world are driving a dramatic increase in the prevalence of type 2 diabetes. Consequently, there is increasing interest in defining the target population and developing strategies for preventing or delaying the disease. Impaired glucose tolerance (IGT), an asymptomatic condition early in the disease continuum of dysglycemia, is the best target for intervention, as it is a strong predictor for the development of both type 2 diabetes and cardiovascular disease (CVD). Identifying individuals likely to have IGT using risk-prediction tools is simple and cost-effective; diagnosis can be confirmed with an oral glucose tolerance test. Numerous trials have examined the benefits of intervention in IGT populations. Lifestyle modification and some pharmacologic therapies, such as acarbose, have been shown to significantly reduce disease progression. Acarbose therapy has also been associated with significant reductions in cardiovascular events and new cases of hypertension. Trials assessing the potential preventive effects of various therapies are ongoing, but current evidence confirms that early intervention in individuals with IGT can reduce the risks of type 2 diabetes and CVD. Identification of high-risk individuals should therefore be standard in general practice and, if IGT is diagnosed, therapeutic intervention should be initiated promptly.