Current Diabetes Reviews - Volume 9, Issue 1, 2013

Diabetic retinopathy (DR) is the leading cause of visual loss in people aged 30 to 69 years. Most authorities recommend screening of the ocular fundus to prevent severe visual loss. The increasing incidence of diabetes mellitus and fewer ophthalmologists in many countries is leading to inadequate screening. Establishing an adequate system for DR screening is a complex issue and represents a challenge for most health authorities. To alleviate the burden of DR screening for most health systems, some investigators have suggested that general practitioners (GPs) perform the initial screenings. The aim of this article was to review the current status of DR screening performed by GPs using non-mydriatic retinography. The five studies analyzed in this review indicated that after adequate training GPs can be effective and reliable screeners of DR using non-mydriatic retinography. Including GPs in the screening model would be a useful way to alleviate the increasing demands of ophthalmic care resulting from the increased prevalence of diabetes mellitus. In addition, GPs would have full control of the diabetic process, which could bolster their motivation and confidence in other areas of diabetes care and medical practice.

Diabetes is a chronic disease with a worldwide increasing trend. Foot complications, closely related to neuropathy and obstructive peripheral vascular disease, are responsible for more than 1 million of leg amputations every year. Foot infection can dramatically increase the risk of amputation. Although many ulcer classification systems have been proposed to stratify the severity of the infectious process, the definition of a specific therapeutic approach still remains an unsolved problem. A Diabetic Foot Triage and an Integrated Surgical Protocol are proposed to identify a diagnostic flowchart and a step-by-step surgical protocol that can be applied in the treatment of diabetic foot infection. Considering the rapid climbing of multidrug resistant strains it is very important to rationalize the use of antibiotics utilizing them only for the treatment of true infected ulcers. PAD is widely considered the most important factor conditioning the outcome of a diabetic foot ulcer. Currently no randomized control trials are reported in the international literature directly comparing open versus endovascular revascularisation in diabetic patients with CLI. Insufficient data are available to demonstrate whether open bypass surgery or endovascular interventions are more effective in these patients. A decisional flow chart in choosing the best revascularization strategy in diabetic patients with CLI is proposed. Goals and technical aspects of emergency and elective surgical procedures in diabetic foot are analysed to evaluate critical aspects and to suggest proper surgical choices.

Pancreatic β-cell dysfunction plays an important role in the pathogenesis of both type 1 and type 2 diabetes. Insulin, which is produced in β-cells, is a critical regulator of metabolism. Insulin is synthesized as preproinsulin and processed to proinsulin. Proinsulin is then converted to insulin and C-peptide and stored in secretary granules awaiting release on demand. Insulin synthesis is regulated at both the transcriptional and translational level. The cis-acting sequences within the 5' flanking region and trans-activators including paired box gene 6 (PAX6), pancreatic and duodenal homeobox- 1(PDX-1), MafA, and β-2/Neurogenic differentiation 1 (NeuroD1) regulate insulin transcription, while the stability of preproinsulin mRNA and its untranslated regions control protein translation. Insulin secretion involves a sequence of events in β-cells that lead to fusion of secretory granules with the plasma membrane. Insulin is secreted primarily in response to glucose, while other nutrients such as free fatty acids and amino acids can augment glucose-induced insulin secretion. In addition, various hormones, such as melatonin, estrogen, leptin, growth hormone, and glucagon like peptide-1 also regulate insulin secretion. Thus, the β-cell is a metabolic hub in the body, connecting nutrient metabolism and the endocrine system. Although an increase in intracellular [Ca2+] is the primary insulin secretary signal, cAMP signaling- dependent mechanisms are also critical in the regulation of insulin secretion. This article reviews current knowledge on how β-cells synthesize and secrete insulin. In addition, this review presents evidence that genetic and environmental factors can lead to hyperglycemia, dyslipidemia, inflammation, and autoimmunity, resulting in β-cell dysfunction, thereby triggering the pathogenesis of diabetes.

Diabetes ketoacidosis (DKA) should be managed following clear written guidelines. However, evidence suggests that healthcare professionals do not always adhere strictly to the agreed guidelines. Objective: This investigation aimed to review the management of DKA in a hospital setting, to assess what DKA treatment was implemented and its effectiveness on patient care. As a result of the study, it was also anticipated that the data would highlight other matters of interest, such as whether certain categories of people are more prone to DKA. Method: A retrospective audit was carried out on patients' case notes in hospitals within the East Midlands, UK. This method prevents study outcomes being swayed because DKA management has already taken place. To reduce selection bias the most recent available case notes were selected. All patients aged 39 and under who were admitted to the emergency department with DKA in the 3 year period between 1st August 2009 and February 2012 had their case notes examined - 142 cases of DKA came within this category. Results: It was found that the DKA protocol being implemented was not based on the most up-to-date evidence available. It was also established that despite the existence of a hospital protocol, some healthcare professionals failed to follow the guidelines. This particular finding was confirmed to be statistically significant with a p value of 0.0409. Additionally, Actrapid was the only intravenous insulin used, despite inadequate research on the most effective insulin. Furthermore, three groups of people were shown to be most ‘at risk’ in this study, and thus more prone to DKA. Conclusion: To improve DKA management and increase the effectiveness and safety of practice for patients, a comprehensive, clear, up-to-date protocol, along with better designed documentation, needs to be introduced and applied rigorously, thus standardising DKA management care. Moreover, it is important that when new guidelines and associated documentation are introduced, that healthcare professionals are made aware of them and are appropriately trained in their use.

Diabetic nephropathy is the leading cause of end-stage renal disease in the United States. The progression of kidney disease in patients with diabetes can take many years, and interventions such as glycemic control, blood pressure control, and inhibition of the renin-angiotensin-aldosterone system have been shown to slow this progression. Despite the implementation of these strategies, the number of patients with diabetes that ultimately develop end-stage renal disease remains high. Recent investigation has focused on the optimization of renin-angiotensin-aldosterone system blockade in patients with diabetic nephropathy using combinations of drugs that target this pathway. Additional investigation has focused on the potential of novel therapies that either target various pathways upregulated by hyperglycemia or other targets believed to promote progression of diabetic nephropathy such as the endothelin system, inflammation and vitamin D receptors. This review article addresses some of the well-established principles regarding the progression and accepted management of diabetic nephropathy and includes current updates on the most recent clinical research trials exploring novel therapeutics in this field.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) is the treatment of choice for patients with tumor characteristics within the Milan criteria associated with Child B or C cirrhosis. LT provides the best cure for both the tumor and the cirrhosis. There have been several emerging reports that new-onset diabetes mellitus (NODM) after transplantation (NODAT) is one of the most negative predictive factors for low survival rate and related co-morbidities. Little is known about the onset of NODM in post-transplant patients and, overall, whether the pathogenesis of NODM differs from that known for the general population. Principally, it is still unknown whether NODAT is related to the primary hepatic disease, the surgical procedures, immunosuppressive treatments, or is it due to the donor liver. This review will focus on the identification of factors, in the setting of LT, which may lead to the development of NODM. Early prevention of these factors may abate the incidence of NODM and positively impact survival rate, and thus ameliorate the worsening of cardiovascular risk factors which usually occur after LT.

There are many reasons to suspect a genetic influence on the development and progression of diabetic retinopathy, including substantial variability in disease severity among patients with similar risk factors. Linkage studies have suggested associations with chromosomes 1, 3, 12 and others. The most studied individual genes are those encoding vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products, all of which have shown statistically significant associations in multiple series from various parts of the world. At this time, no definite genetic associations with diabetic retinopathy have been consistently reported. This may be due to small sample sizes, differences in study design, underlying genetic differences between study populations, or other factors. As we continue to collect data, these relationships may become more clear.