Current Diabetes Reviews - Volume 6, Issue 2, 2010

Overweight and obesity is a growing “world-wide epidemic problem”. Because as many as, two-third of the adult population and a growing number of children are overweight. The prevalence of diabetes, especially type 2 diabetes and hypertension have significantly increased with the prevalence of obesity. Obesity accompanying type 2 diabetes and hypertension are known to be closely linked with insulin resistance and elevated sympathetic nervous activity. It has been well documented that obesity, hypertension, and diabetes are high risk factors for subsequent cardiovascular and renal complications. Many patients are both diabetic and hypertensive; while they are obese, but not all diabetic patients have hypertension, indicating that insulin resistance is not only a mechanism for blood pressure elevation in diabetichypertensive patients. Several investigators have reported that sympathetic nervous activation relates to cardiovascular complications in patients with hypertension, diabetes, and obesity, and that sympathetic nerve activity accompanying insulin resistance is closely linked with left ventricular hypertrophy in healthy subjects. In addition, sympathetic nerve activation may predict future renal injury in healthy normotensive subjects. These findings suggest that elevated sympathetic nerve activity associated with insulin resistance may contribute to the onset and maintenance of cardiovascular and renal complications in diabetes, and hypertension in obesity. Further, genetic polymorphisms of the β2- and β3-adrenoceptor gene have been associated with type-2 diabetes and insulin resistance in many epidemiological studies and might be another factor responsible for the close relationship between insulin resistance and heightened sympathetic nerve activity. Thus, focusing on the interactions between insulin resistance, sympathetic nervous activity and β-adrenoceptor polymorphisms might help in understanding the precise relationships between insulin resistance and sympathetic nerve activity in type 2 diabetes and obesity-related hypertension. The purpose of this article is to provide a synthesis of the current findings on the mechanisms of the onset and maintenance of cardiovascular and renal complications in obesity, diabetes and hypertension. A better understanding of the relationships of sympathetic nervous system activity and insulin resistance might help with the clinical treatment of diabetes and hypertension in obesity. Further, to clarify the pathogenesis and mechanisms of the association between obesity, diabetes, and hypertension may lead to reductions in cardiovascular and renal risk.

In recent years, the number of people suffering from diabetes has increased notably. This increase has led to an augmentation in secondary diseases; amongst them, diabetic nephropathy (DN) is one of the most relevant pathologies. DN provokes a decrease in glomerular filtration rate, which ends up in chronic renal failure. In the developed countries, DN is the first cause of chronic renal failure needing replacement therapy. Thus, this disease is responsible for a remarkable part of the public health costs in the Western countries. All of these facts have encouraged many scientists to perform their research on mechanism causing DN, improving our knowledge of its pathogenesis. In this review we summarize the most relevant facts on the physiopathology of DN.

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism in which glucose is underutilized, producing hyperglycemia. The latter complications of diabetes mellitus include microvascular complications the major microvascular complications, retinopathy and nephropathy, are the more important causes of blindness and end-stage renal disease in Europe. Different risk factors such as diabetes duration, blood pressure and lipid control have consistently been shown to correlate with both microvascular complications for diabetes. Despite the efforts of studies to correlate the two major diabetes mellitus microvascular complications, retinopathy and nephropathy, the relationship has not so far been clearly described. However, the currently literature data suggest that the presence of a pre-existing microvascular complication (retinopathy or nephropathy) may contribute to the development of another, especially in DM1 patients. More prospective studies are needed if we are to know the exact mechanism of how these diabetic microvascular diseases correlate, and if we are to develop a scoring system for predicting the development of those complications that will allow us to identify the patients at risk, with its consequent positive impact on patients' quality of life. The aim of the present study is to review the literature on the diagnosis, epidemiology, pathology, and risk factors in diabetic nephropathy and retinopathy, and then a revision of the possible relation between renal and retinal diabetic microangiopathy.

Background: Patients without a history of diabetes often develop hyperglycemia during an acute coronary syndrome (ACS). New onset of hyperglycemia (NH) is associated with higher mortality both in the short and long-term. Aim: We performed a systematic review and meta-analysis of observational studies to investigate the association between NH and mortality in patients with ACS. In-hospital, 30-day and long-term mortality were analyzed separately. Methods: We searched MEDLINE for prospective studies of patients with ACS reporting the association between NH and mortality, using Research Methodology Filters. This was supplemented by hand searching reference lists of retrieved articles. We determined study eligibility and conducted data abstraction independently and disagreements were resolved by consensus. We pooled odds ratios (OR) from individual studies using a random effects model. Results: Our search strategy identified 24 studies. The prevalence of NH varied widely between 3-71% depending on the definition of NH used. NH significantly increased the risk of in-hospital (OR 3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies, 10673 patients), 30-day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4 studies, 101447 patients), and long-term (up to 108 months) mortality (OR 2.02, 95% CI: 1.62-2.51; p < 0.0001, I2=79.4%; 12 studies, 102099 patients). Conclusions: In patients without a prior diagnosis of diabetes who are admitted to hospital for ACS, NH increases the risk of both short and long-term mortality. These data highlight the need for further studies addressing the control of blood glucose levels in patients with ACS. Summary: Patients without history of diabetes may develop new hyperglycemia (NH) on admission to hospital for AMI. We systematically reviewed the prognostic impact of NH on short- and long-term mortality in patients without prior diagnosis of diabetes who attended the hospital for ACS. We identified 24 outcome studies which met a set of pre-specified criteria. Prevalence of NH ranged from 3% to 71% according to different thresholds of blood glucose concentrations. NH significantly increased the risk of in-hospital (OR 3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies, 10673 patients), 30-day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4 studies, 101447 patients)), and long-term (up to 108 months) mortality (OR 2.02, 95% CI: 1.62-2.51; p < 0.0001, I2=79.4%; 12 studies, 102099 patients).

A reduced fall in nocturnal blood pressure (BP) (i.e. non-dipping) has been related to an increase in target organ damage and cardiovascular (CV) events. Numerous studies have shown that non-dipping is highly prevalent in patients with type 1 and 2 diabetes mellitus. In this paper we reviewed recent literature and our personal data on the prevalence and clinical correlates of abnormal diurnal BP rhythm in diabetic patients; in particular we examined the association of this condition with renal, cardiac, and vascular pre-clinical organ damage as well as CV prognosis. A consistent body of evidence based on cross-sectional and longitudinal studies indicates that the lack of the physiologic nocturnal fall in BP may be considered a true clinical trait, a reliable marker of preclinical CV and renal disease and an independent predictor of future CV events. Thus, in the diabetic setting ambulatory BP monitoring (ABPM) should be regarded as a pivotal tool for improving CV risk stratification and therapeutic interventions.

Diabetes mellitus complicates 1-2% of all pregnancies but is associated with high a perinatal morbidity and mortality. Gestational diabetes affects up to 4% of pregnancies and is associated with foetal macrosomia (large for dates). Foetal growth is a complex process influenced by genetics, maternal factors, uterine environment and maternal and foetal hormonal status. Infants of pre-gestational diabetic mothers have an additional influence of maternal fluctuations in glycaemia. The purpose of this paper is to review maternal and foetal growth factors, including insulin, in the aetiology of macrosomia in diabetic pregnancy. Placental Growth Hormone is the major growth hormone secreted during human pregnancy. Leptin may have a role in satiety. Resistin was originally proposed as the link between obesity and diabetes but is now thought to have a more complex role. These hormones and their actions on human foetal growth are reviewed in depth with particular reference to both pre-gestational (type 1 and type 2 diabetes) and gestational diabetes. Previously, increased foetal weight in infants of diabetic mothers was thought to be as a result of maternal hyperglycaemia. It is now evident that the control of foetal growth, in normal as well as diabetic pregnancies, is far more complex than previously understood.

Some immigrant groups in Europe show an increased prevalence of diabetes, e.g. South Asians in the UK and Moroccans and Turks in the Netherlands. This study aimed at reviewing the literature among immigrants in the Nordic countries. Search was performed primarily of Medline through PubMed, and secondarily of other databases and by using information from reference lists. Terms used were: “Diabetes Mellitus”, “Immigrant”, and “Nordic countries” or “Scandinavia” or “Denmark”, “Finland”, “Iceland”, “Norway” or “Sweden”. Altogether 17 articles on diabetes were found. Excess risk of diabetes was found in non-European immigrant groups, especially from the Middle East and South Asian regions, in some cases 10 times the risk of the indigenous population, with the highest relative risks among women. No excess risk was found among European immigrants, with the possible exception of Finnish women. Conflicting results were found in studies with a low number of diabetic cases, with a failure to show statistically significant excess risks among non-European groups. There were also some other methodological problems, e.g. low participation rate in populationbased clinical studies, and probable underestimation of known diabetes by self-report. A genetic sensitivity seems likely in the Middle East and South Asian groups, combined with lifestyle factors.