Epidemiology of Diabetic Foot Ulcers and Amputations in Romania: Results of a Cross-Sectional Quality of Life Questionnaire Based Survey

This is a post hoc analysis of quality of life in diabetic neuropathy patients in a cross-sectional survey performed in 2012 in Romania, using the Norfolk QOL-DN in which 21,756 patients with self-reported diabetes were enrolled. This current analysis aims to expand research on the diabetic foot and to provide an update on the number of foot ulcers found in Romania. Of the 21,174 patients included in this analysis, 14.85% reported a history of foot ulcers and 3.60% reported an amputation. The percentage of neuropathy patients with foot ulcers increased with age; the lowest percentage was observed in the 20-29-year age group (6.62%) and the highest in the 80-89-year age group (17.68%). The highest number of amputations was reported in the 70-79-year age group (largest group). Compared to patients without foot ulcers, those with foot ulcers had significantly higher scores for total DN and all its subdomains translating to worse QOL ( < 0.001). This analysis showed a high rate of foot ulcers and amputations in Romanian diabetic patients. It underscores the need for implementation of effective screening and educational programs

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Benfotiamine: Commentary and update on recent studies

The thiamine prodrug benfotiamine (S-benzoylthiamine-O-monophosphate) has been shown to prevent the formation of advanced glycation endproducts (AGEs), thus decreasing hyperglycaemia-induced damage and neuropathic sensory symptoms. However, recent studies have yielded contradictory results. Other studies emphasize the need for further research on the potential of benfotiamine in the treatment of vascular and diabetes complications. Currently, benfotiamine is considered to be a pathogenetic treatment in counteracting oxidative stress and hyperglycaemia-induced metabolic changes that lead to neuropathy

Neuropathy in chronic kidney disease

Chronic kidney disease (CKD) is characterised by an increasing prevalence, with the current prevalence of approximately 10 % in adults > 20 years in Western industrialized countries. In patients with CKD, frequently both the central nervous system (CNS) and the peripheral nervous system (PNS) are affected. Uremia, accumulation of AGE and oxidative stress, hyperkalemia, insulin resistance, adipocytokines, and erythropoietin deficiency and resistance have been identified as potential triggering factors. An impaired cerebral cognitive function in uremic patients is demonstrable even in clinically asymptomatic stages. Typical neurological sequelae include, among others, uremic encephalopathy, dialysis disequilibrium syndrome, and uremic polyneuropathy. In general, initiation of renal replacement treatment is suggested as the most promising therapeutic approach. Additionally, symptomatic treatment of neuropathic pain with first line drugs, such as gabapentin, pregabalin, tricyclic antidepressants or duloxetine, remains a reasonable approach. With respect to the important role of inflammation and oxidative stress in the further deterioration of renal function and nervous damage, additional treatment with benfotiamine may be considered as a pathogenesis-oriented approach

Neuropathy in chronic kidney disease

Chronic kidney disease (CKD) is characterised by an increasing prevalence, with the current prevalence of approximately 10 % in adults > 20 years in Western industrialized countries. In patients with CKD, frequently both the central nervous system (CNS) and the peripheral nervous system (PNS) are affected. Uremia, accumulation of AGE and oxidative stress, hyperkalemia, insulin resistance, adipocytokines, and erythropoietin deficiency and resistance have been identified as potential triggering factors. An impaired cerebral cognitive function in uremic patients is demonstrable even in clinically asymptomatic stages. Typical neurological sequelae include, among others, uremic encephalopathy, dialysis disequilibrium syndrome, and uremic polyneuropathy. In general, initiation of renal replacement treatment is suggested as the most promising therapeutic approach. Additionally, symptomatic treatment of neuropathic pain with first line drugs, such as gabapentin, pregabalin, tricyclic antidepressants or duloxetine, remains a reasonable approach. With respect to the important role of inflammation and oxidative stress in the further deterioration of renal function and nervous damage, additional treatment with benfotiamine may be considered as a pathogenesis-oriented approach