Current Diabetes Reviews - Volume 10, Issue 2, 2014

Latin America is among the regions with the highest diabetes-related burden. Research and treatment programs have increased in number and complexity in recent years, but they are focused in type 2 diabetes, because this condition explains a large proportion of the cases. In contrast, the information regarding the epidemiology of type 1 diabetes is scant in this area. Here, we analyze the available information on this topic and identify potential areas of opportunity to generate new knowledge through the study of type 1 diabetes in Latin Americans. Both, the prevalence and the incidence of type 1 diabetes, are lower in Latin American countries compared to that reported in Europe, North America, southern Asia and northern Africa. Biologic and methodological factors may explain the smaller contribution of type 1. The presence of some putative 'protective' environmental exposures or the absence of those prevalent in a region may explain the lower type 1 diabetes prevalence observed in most Latin American countries. However, the number and quality of the diabetes registries are not enough in this region. During the past decade, the incidence of type 1 diabetes has grown worldwide. The same trend has been reported in Latin America. This epidemiologic transition is a unique opportunity to identify interactions between rapidly changing environmental factors in subjects with different genetic backgrounds (such as the admixed Latin American populations). Finally, on-going therapeutic initiatives in this region are highlighted.

Lower extremity ulcers represent a serious and costly complication of diabetes mellitus. Many factors contribute to the development of diabetic foot. Peripheral neuropathy and peripheral vascular disease are the main causes of foot ulceration and contribute in turn to the growth of additional risk factors such as limited joint mobility, muscular alterations and foot deformities. Moreover, a deficit of balance, posture and biomechanics can be present, in particular in patients at high risk for ulceration. The result of this process may be the development of a vicious cycle which leads to abnormal distribution of the foot's plantar pressures in static and dynamic postural conditions. This review shows that some of these risk factors significantly improve after a few weeks of exercise therapy (ET) intervention. Accordingly it has been suggested that ET can be an important weapon in the prevention of foot ulcer. The aim of ET can relate to one or more alterations typically found in diabetic patients, although greater attention should be paid to the evaluation and possible correction of body balance, rigid posture and biomechanics. Some of the most important limitations of ET are difficult access to therapy, patient compliance and the transitoriness of the results if the training stops. Many proposals have been made to overcome such limitations. In particular, it is important that specialized centers offer the opportunity to participate in ET and during the treatment the team should work to change the patient’s lifestyle by improving the execution of appropriate daily physical activity.

Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. The diabetes Control and Complications Trial reported that 27% of patients affected by type 1 diabetes develop DME within 9 years of onset. Other studies have shown that in patients with type 2 diabetes, the prevalence increased from 3% to 28% within 5 years of diagnosis to twenty years after the onset. At the present time, despite the enthusiasm for evaluating several new treatments for DME, including the intravitreal therapies for DME (e.g., corticosteroids, and anti-VEGF drugs), laser photocoagulation remains the current gold standard and the only treatment with proven efficacy in a wide range of clinical trials for this condition. Despite being the standard technique for comparison and evaluation of the emerging treatments, we have generally poor understanding of the ETDRS recommendations, and we often forget about the results of laser in DME. The purpose of this review is to update our knowledge on laser photocoagulation for DME with an extensive review of the ETDRS results and discuss the laser techniques. Furthermore, we will describe the new developments in laser systems and review the current indications and results. Finally, we will discuss the results of laser treatments versus the current pharmacological therapies. We conclude by trying to provide a general overview that which laser treatment must be indicated and what types of lasers are currently recommended.

Aim: The relationship between elevated serum uric acid level and metabolic syndrome (MS) has been debated. There is no data concerning this relation in Iranian population-based studies. The aim of this study was to determine the prevalence of hyperuricamia and its association with MS in type 2 diabetes mellitus (DM). Patients and Methods: This was a cross- sectional study in 1978 diabetic patients. Hyperuricamia was defined as uric acid ≥ 7 and ≥ 5.5 mg/dl for men and women respectively. Diagnosis of metabolic syndrome was based on ATPIII criteria. Clinical and biochemical parameters in hyperuricaemic and normouricaemic patients compared with other. Results: The prevalence of hyperuricaemia and metabolic syndrome was 12.7% and 65.5% respectively. The prevalence of MS significantly increased in the highest quartile of uric acid levels compared with lowest quartile (74.4% vs 55.9%, p<0.001). Serum uric acid had positive association with cholesterol, triglyceride, non-HDL cholesterol and a negative association with fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C) and HDL cholesterol. Possible independent biochemical predictors of hyperuricamia were cholesterol, triglyceride, creatnine and FBS. Conclusion: The prevalence of MS and its components increases with increasing levels of uric acid in type 2 diabetes. Regular assessment of uric acid could give information for predicting of MS and prevention of atherosclerosis in type 2 diabetes.

The most robust and frequently reported cognitive deficits in type 2 diabetes (DM2) are those that relate to memory. Behavioural research has identified a number of potential contributory physiological factors, including abnormalities in glucose metabolism, such as hyperglycaemia and hypoglycaemia. The impact of these mechanisms on memory has been further investigated through the use of both structural and functional neuroimaging. Structural brain imaging has indicated that memory impairments in DM2 are associated with global atrophy of the brain. Further data suggest that localised atrophy in the hippocampal area, a brain region critical to memory formation and consolidation, may be primarily responsible for the memory deficits seen in this population. Functional imaging data has corroborates these findings, with functional magnetic resonance imaging (fMRI) suggesting reduced connectivity between the hippocampus and surrounding brain regions, particularly the frontal and temporal gyri. Despite this, little functional neuroimaging research has directly investigated differences in regional brain activity between healthy and DM2 participants whilst memory tasks are being performed. By using neuroimaging techniques to their full potential, we can acquire a fuller, more comprehensive picture of the impact that DM2 has on memory.

The prevalence of diabetes is increasing world-wide. Tight glycaemic control has been shown to reduce diabetes complications in a number of landmark trials. Apart from increasing the risk of microvascular and macrovascular disease, poor glycaemic control is also associated with cognitive and memory impairment as well as with mood disturbance. However, tighter glycaemic control with conventional anti-hyperglycaemic medication is also associated with increased risk of hypoglycaemia. There is increasing evidence that hypoglycaemia is much more than a troublesome inconvenience. Indeed it is associated with acute cognitive impairment, dementia, increased risk of falls, rebound hyperglycaemia with consequent loss of glycaemic control, acute coronary syndrome and increased mortality. Hence, a very difficult balance needs to be achieved so as to achieve the best glycaemic control possible, whilst avoiding hypoglycaemia. This paper will briefly discuss the potential benefits of tight glycemic control and reviews the risks associated with hypoglycaemia. A paradigm shift in diabetes care may be needed; use of newer anti-hyperglycemic agents with low hypoglycaemia risk may allow us to achieve good control in most patients whilst avoiding the serious consequences of hypoglycaemia. This may be especially important in those at significant risk of hypoglycaemia (e.g. those with brittle diabetes) or of its consequences such as elderly patients, those in certain occupations or those with cardiovascular disease or epilepsy.

Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor- based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management.