Current Diabetes Reviews - Volume 5, Issue 3, 2009

Pregnancy in a diabetic woman brings about many changes that can lead to the development of diabetic retinopathy (DR) or worsening of pre-existing disease. In some patients this may develop into sight threatening disease which, if not treated adequately, can cause devastating visual impairment. There is a lack of established guidelines for screening these patients during pregnancy. In this article we discuss the physiological changes during pregnancy that contribute to worsening of diabetic retinopathy and review the relative contribution of risk factors to the underlying pathological processes. It is important to identify and treat any pre-existing retinopathy in diabetic women considering pregnancy and optimise glycaemic control prior to conception. Rapid tightening of glycaemic control after conception is associated with a less favourable outcome. Based on the existing literature we suggest guidelines for diabetic retinopathy screening for women during pregnancy. Established sight-threatening retinopathy should be treated at an earlier stage in pregnant women compared to non-pregnant diabetics with a similar disease.

The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ß-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ß-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

Diabetes is one of the major causes of morbidity and mortality in the Western world and it currently affects 35 million people in the US alone. Cardiovascular and renal complications of diabetes, Type I and II, account for much of this morbidity, and are now known to be the end result of a complex interplay of pathophysiological processes. These include haemodynamic and metabolic abnormalities such as endothelial dysfunction, inflammation, vasoconstriction, oxidation and fibrosis. For some time it has been difficult to elucidate whether these processes and subsequent dysfunction in organs such as the heart and kidney is due to processes that often coexist with diabetes, such as hypertension. However, it is now clear that there is a distinct pro-inflammatory and pro-fibrotic state in diabetes, which may in addition be complicated by synergistic disease processes. The use of statins in diabetes has been of interest for a while due to the known effect of statins on inflammatory and fibrotic pathways. This review covers the clinical evidence for the use of statins in diabetes, the major known pathophysiological processes that occur in diabetic organ disease and discusses the known and putative effects of statins on these pathways. It concludes with a brief discussion of some early and yet unpublished work regarding the addition of statin therapy to angiotensin inhibition therapy in diabetic disease.

Objectives: The aim of this review was to examine the prevalence, incidence and risk factors of chronic heart failure in the type 2 diabetic population. Methods: A systematic search of studies related to chronic heart failure (CHF) in the diabetic population was performed using medical databases. Results: 1) The prevalence of CHF in the diabetic population was approximately 10-23% in the large previously studied cohort. This was about three times higher than in nondiabetic control groups. 2) The incidence of CHF in diabetes varied greatly. It was influenced by the time of follow-up, the mean age of patients, the state of metabolic control and the complications of diabetes. The incidence of CHF in patients with diabetes was approximately two-fold greater than in the non-diabetic population. 3) The main risk factors of CHF in the type 2 diabetic population were age, hemoglobin A1c (HbA1c), coronary heart disease, hypertension, microalbuminuria and obesity. Conclusions: The prevalence and incidence of CHF were found to be high in the diabetic population, and the risk factors of CHF were somewhat different from those in the general population.

Gestational diabetes mellitus (GDM) and pre-gestational diabetes are known to pose risks to the mother and developing fetus, often related to abnormal fetal growth. One potential mediator of maternal effects on fetal growth is Placental Growth Hormone (PGH). PGH is produced by the syncytiotrophoblast and found predominantly in the maternal circulation. It progressively replaces pituitary growth hormone (hGH) in the human maternal circulation from midgestation onwards, peaking towards term. PGH appears to be an important potential regulator of maternal insulin resistance in human pregnancy and may influence fetal growth both by modifying substrate availability and through paracrine actions in the placental bed. The details of PGH regulation remain relatively poorly understood, but current evidence does suggest a central role in growth restricted pregnancies. There is currently less evidence of a pathophysiologic role in production of the macrosomic fetal phenotype commonly seen in response to hyperglycaemia, although our recent in vitro studies do raise the possibility of feto-placental feedback as a mechanism of growth modulation.

The parallel epidemics of obesity and Type 2 diabetes (T2DM) are progressing rapidly in Australia. The high prevalence of obesity and sedentary lifestyle in the population, compounded by later child bearing, has led to an increase in the prevalence of T2DM pre-dating pregnancy. In some centers, pregnant women with T2DM now outnumber those with type 1 diabetes (T1DM). Although there is controversy as to whether T2DM is associated with worse outcomes than T1DM in pregnancy, modern reports clearly acknowledge the seriousness of this condition. There is a clear association between obesity and adverse pregnancy outcomes (cesarean section, gestational diabetes, hypertensive disorders, birth defects and prematurity). Aside from obesity and the metabolic syndrome, additional factors may contribute to these adverse outcomes: A lack of preconception planning, a failure to achieve tight glycaemic control early in pregnancy and socio-economic disadvantage. It's likely that obesity and diabetes have compounding effects on pregnancy outcomes. In this review, we evaluate both the underlying pathogenesis of T2DM and obesity in the pregnancy context and the adverse clinical maternal and perinatal outcomes described in pregnancies complicated by maternal T2DM and obesity. We highlight the need for a comprehensive strategy to improve clinical outcomes in these pregnancies.

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the “histone code” describes the idea that specific patterns of post-translational modifications to histones act like a molecular “code” recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as “chemical chaperones” to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes.