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In this retrospective case-control study conducted in Cluj-Napoca, Romania, we assessed the effect of ulcerations/amputations on hospitalization costs of patients with diabetes. Patients with (Group 1) or without (Group 2) ulcerations/amputations (case-control ratio 3:1) admitted to a single diabetes center between 2012–2017 were included. The effects of hospitalization days, age, duration of diabetes, body mass index and glycated hemoglobin (HbA1c) on total costs was explored using a multivariate linear regression analysis, enter model. Overall, 876 patients were included (Group 1: 682, 323 [47.4%] with amputations, Group 2: 194). Median (interquartile range) total expenses in Group 1 were 40% higher compared to Group 2 (€724 [504, 1186] vs €517 [362, 645], p &lt, 0.001). Significant differences were observed between hospitalization costs (p &lt, 0.001), cost of food (p &lt, 0.001), medication (p = 0.044), drugs administered at the emergency room/intensive care unit (p &lt, 0.001) and other expenses (p = 0.003). Hospitalization costs represented 80.5% of total expenses in Group 1 and 76.3% in Group 2. In multivariate analysis, hospitalization days influenced significantly the total costs in both groups (p &lt, 0.001), in Group 2, the effect of HbA1c was also significant (p = 0.021). Diabetic foot ulcers and subsequent amputations most likely impose a significant economic burden on the Romanian public healthcare system.

Lower urinary tract symptoms (LUTS) are commonly reported by men and women with diabetes and may share a common pathogenic mechanism with diabetic peripheral neuropathy (DPN). We aimed to evaluate associations between DPN and self-reported LUTS in a cohort of Romanian patients with diabetes phenotyped for DPN with the Michigan Neuropathy Screening Instrument (MNSI). Clinical DPN was defined as MNSI exam score of >2; symptomatic DPN as MNSI questionnaire score of ≥4. LUTS was assessed with the validated American Urological Association Symptom Index and defined as 0-7 none/mild and ≥8 moderate/severe. Preliminary data is shown for 174 participants [51% men, mean age 67 years, 95% type 2 diabetes, mean diabetes duration 16 years, mean hemoglobin A1c (HbA1c 8%)]. Sixty% and 64% met the criteria for clinical and symptomatic neuropathy, respectively and 53% of men and 47% of women reported moderate/severe LUTS. MNSI questionnaire scores were significantly associated with LUTS in both men (p Disclosure C.L. Vonica: Other Relationship; Self; AstraZeneca. C.I. Bondor: Consultant; Self; Wörwag Pharma. D. Sima: None. D.T. Cosma: Other Relationship; Self; Wörwag Pharma. I. Veresiu: None. N. Gavan: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. A.V. Sarma: None. Funding Woerwag Pharma GmbH & Co. KG

Background and Aim: Type 2 diabetes (T2DM) has been associated with hypertension (HTN) and elevated high-sensitivity C-reactive protein (hsCRP), but the possible implication of blood pressure (BP) variability in increasing hsCRP in T2DM are incompletely understood. We aimed to assess the association between hsCRP and BP variability during 24-hour ambulatory BP monitoring in T2DM and healthy control subjects. Material and Method: The cross-sectional study included data from T2DM patients with normal BP (n=9), controlled HTN (n=46), uncontrolled HTN (n=20), and healthy controls (n=11). HsCRP was assessed using ELISA technique. All subjects underwent 24-hour ambulatory BP monitoring; BP variability was calculated using standard deviation. Results: We found that hsCRP was associated with daytime and 24-hours systolic and diastolic BP variability. Higher hsCRP were observed in T2DM patients with uncontrolled HTN and high BP variability compared to the other three groups. In multiple regression analysis, hsCRP was predicted by daytime and 24-hour diastolic BP variability. Conclusions: Our findings suggest that high hsCRP was associated with increased ambulatory BP variability in T2DM and control subjects. The contribution of both hsCRP and BP variability to cardiovascular risk stratification in T2DM needs to be evaluated in prospective studies.

Aims An imbalance in advanced glycation end products (AGEs) and NADH formation has been associated with diabetic chronic kidney disease (CKD) and cardiovascular disease (CVD). No data have been reported on simultaneous measurement of AGEs and NADH in type 2 diabetes (T2DM) patients. We aimed to compare AGEs, NADH and the AGEs-to-NADH ratio in T2DM and controls, and to assess its relationship with diabetic CKD and CVD. Material and methods In this cross-sectional study, we measured serum AGEs (370/435 nm) and NADH (370/460 nm) in T2DM patients (n = 63) and controls (n = 25) using fluorescence spectroscopy. The AGEs-to-NADH ratio was analyzed according to diabetic CKD and CVD. Results We found significantly higher AGEs-to-NADH ratio in T2DM compared to controls. The AGEs-to-NADH ratio was significantly associated with triglycerides, blood glucose, HDL-cholesterol, estimated glomerular filtration rate. The AGEs-to-NADH ratio was a significant predictor for the presence of diabetic CKD and CVD when using ROC curves. Multivariate analysis showed that triglycerides and the presence of T2DM were predictors for the AGEs-to-NADH ratio. Conclusions These findings suggest that the fluorophores AGEs-to-NADH ratio could be a new biomarker for the presence of diabetic CKD and CVD.

Background and aims. Resistant hypertension is defined as failure to achieve blood pressure lower than 140/90 mmHg when using three antihypertensive agents or controlled blood pressure with four or more drugs. We aimed at assessing the prevalence of resistant hypertension and to describe a type 2 diabetes population with resistant hypertension.Methods. The retrospective observational study included (n=73) type 2 diabetes subjects with resistant hypertension selected from (n=728) subjects admitted to the Centre of Diabetes, Cluj, Romania. Results. The subjects (70% women) had a mean age of 65.0±8.9 yrs. and diabetes duration 11(6-19) yrs. Prevalence of resistant hypertension was 10%. Chronic diabetes complications and cardiovascular disease were present in 77% and 56% of subjects respectively. On admission, antihypertensive drugs used were: angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers 93%, β-blockers 88%, diuretics 78%, calcium channels blockers 59%, adrenergic α-antagonists 11%. Systolic and diastolic blood pressure were lower in the last compared to first admission day. Diuretics and calcium channels blockers were the most frequently newly added antihypertensive agents.Conclusion. Although the prevalence of resistant hypertension in type 2 diabetes did not differ from the general population, we observed that these patients had increased frequency of chronic diabetic complications. Angiotensin-converting enzyme inhibitors or angiotensin II receptors and β-blockers were the most used antihypertensive drugs, while the most frequently newly prescribed drugs were diuretics and calcium channel blockers.

Background and Aims. There is no unanimous opinion regarding the risk factors associated with progression of diabetic retinopathy (DR). We have done a retrospective analysis of risk factors and clinical features associated with DR progression. Material and Methods. This analysis included consecutive patients with moderate non-proliferative or severe retinopathy between December 1, 2013 and May 31, 2014 who had at least two eye examinations before that period. We have collected demographic, clinical and lab data. Results. 51.28% of patients were diagnosed with moderate non-proliferative diabetic retinopathy (NPDR), 24.68% with severe NPDR and 21.05% with proliferative diabetic retinopathy. In 82.16% of cases, DR had progressed. The risk factor correlated with DR progression in the whole group was anemia; hypertension, anemia and diabetes duration were risk factors in type 1 and smoking status at diabetes diagnosis in type 2 diabetes. Total cholesterol, triglycerides, diabetes control and presence of diabetic renal disease were positively but not statistically significant correlated with DR progression. Conclusions. In our study the risk factors correlated with DR progression were hypertension, anemia and diabetes duration in type 1, respectively smoking at diabetes diagnosis in type 2 diabetes. Glycemic goals were achieved in a small number of patients.

Background The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania) study is the first national study analyzing the prevalence of diabetes mellitus (DM) and prediabetes, and their association with cardiometabolic, sociodemographic, and lifestyle risk factors in the Romanian population aged 20–79 years. Methods This was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Sociodemographic, lifestyle, and anamnestic data were collected through self- and interviewer-administered questionnaires, and biochemical assays and oral glucose tolerance tests were performed. Results In all, 2728 participants from 101 clinics of general practitioners were randomly selected, with a probability proportional to population size according to the 2002 Romanian Census. The participation rate was 99.6%. Impaired glucose regulation (prediabetes, known and unknown DM) was found in 28.1% of the study population. The overall age- and sex-adjusted prevalence of DM was 11.6% (95%CI 9.6%–13.6%), of which 2.4% (95%CI 1.7%–3.1%) had unknown DM. The prevalence of DM increased with age and was higher in men than in women. The age- and sex-adjusted prevalence of prediabetes was 16.5% (95%CI 14.8%–18.2%), with the highest percentage in the 60–79 year age group and in women. Obesity, abdominal obesity, dyslipidemia, low education level, and a family history of diabetes were associated with glucose metabolism disorders. Conclusions The PREDATORR study shows a high prevalence of impaired glucose regulation in the adult Romanian population, providing data on the prevalence of DM and prediabetes and their association with several risk factors.

Objective Advanced glycation end products (AGE) contribute to the development of diabetes complications. Their accumulation in skin can be non-invasively assessed by measurement of skin autofluorescence (SAF). Our study investigated whether SAF correlates with measures of diabetic peripheral neuropathy (DPN). Methods In a multi-center study (8 centers), 497 consecutive individuals with diabetes mellitus were investigated. Forearm SAF was measured using the AGE Reader (Groningen, The Netherlands). DPN was assessed using the Toronto Clinical Neuropathy Score (TCNS), the Neuropathy Symptoms Score (NSS) and the Neuropathy Disability Score (NDS). Results (mean ± SD) According to the TCNS, SAF (arbitrary units - AU) was increased in individuals with DPN (TCNS > 5): 2.59 ± 0.56 AU compared with those without DPN (TCNS ≤ 5): 2.45 ± 0.53 AU, (p = 0.04) and significantly increased with the severity of DPN (p = 0.028). Higher SAF was detected in individuals with neuropathic deficits (NDS > 2): 2.58 ± 0.56 AU vs. those without deficits (NDS ≤ 2): 2.45 ± 0.53 AU, (p = 0.009) as well as in individuals with symptoms (NSS > 2): 2.54 ± 0.56 AU vs. those without symptoms (NSS ≤ 2): 2.40 ± 0.47 AU, (p = 0.022). Conclusions Accumulation of AGE in skin is increased in individuals with DPN and progresses with the severity of DPN. Therefore, SAF measurement, an easy-to-use, quick and non-invasive method, might help in identifying subjects at high risk for having DPN.

Background and aim . Morbid obesity represents a proinflammatory and pro-oxidative state associated with dysregulation of adipokines. We aimed to evaluate the circulating levels of chemerin and omentin-1 in morbidly obese (MO) patients and to investigate the relationship between these two adipokines and between each of them and anthropometric, metabolic, oxidative stress and chronic inflammatory parameters. Material and methods . 32 MO patients and 20 controls were investigated in this study. Anthropometric, metabolism parameters, inflammatory markers, oxidative stress indicators as well as chemerin and omentin-1 were measured. Results . Serum levels of chemerin were increased while omentin-1 levels were decreased in MO patients when compared with controls. Chemerin correlated positively with insulin, HOMA-IR, LDL cholesterol and negatively with total antioxidant response. Omentin-1 correlated negatively with tumor necrosis factor alpha and total cholesterol. In a multiple linear stepwise regression analysis we learnt that only HOMA-IR (β=0.70, p

Diabetic neuropathy is a group of clinical syndromes that may occur separately or in various combinations and may affect various components of the nervous system. The involvement of different types of nerve fibers in the natural history of diabetic neuropathy is selective, being considered that the first affected in diabetic neuropathy are small unmyelinated nerve fibers and by measuring the current perceptions threshold (using the Neurometer®) we can quantify the status of three different types of nerve fibers. The aims of our study were to assess diabetic peripheral neuropathy (DPN) by measuring the rapid current perception threshold (R-CPT) using Neurometer, to estimate the prevalence of DPN using this method, and to analyze the possible correlation between R-CPT and clinical, biochemical and metabolic parameters.

Over a decade ago, sildenafil, the first phosphodiesterase type 5 (PDE5) inhibitor, became available and revolutionized the treatment of erectile dysfunction (ED). Ever since, several other agents, such as vardenafil and tadalafil, have enriched the spectrum of therapy offering therapeutic flexibility. The fascinating background of PDE5 inhibitors is that they were initially developed for cardiovascular treatment, and this aspect has lately attracted increasing attention. Both type 2 diabetes mellitus (T2DM) and ED are associated with endothelial dysfunction and an increased risk for cardiovascular disease (CVD). While sudden drops in blood pressure from PDE5 inhibitor use may trigger sympathetic activation with potential negative effects on a damaged cardiovascular system, a growing body of literature suggests that PDE5 inhibitors restore endothelial function, thus representing a potential cardiovascular therapy. This article discusses current use, safety profile and future therapeutic developments of this class of dugs.

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 (p<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.

Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans.Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine.Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% (∗∗P<0.001versus baseline) an effect significantly reduced by benfotiamine treatment to 25%∗§(∗P<0.05versus baseline,§P<0.05versus smoking alone). Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days.Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

objective was to conduct a critical review of the factors that account for psychological insulin resistance (PIR) and of the available strategies to reduce it. Medline, PubMed, Cochrane reviews, PsycInfo, ProQuest, Science Direct, and EBSCO databases were searched and 60 studies were included in the final review. Topics reviewed included: research methods, instruments to assess PIR, PIR in patients and in the medical care team, and proposed strategies for overcoming it. The results showed that a large number of factors account for PIR in patients. The main categories are emotional, cognitive, social/cultural, and interaction with health providers. Physicians mainly delay insulin because they lack knowledge on guidelines or pancreas physiology, they fear inducing hypoglycaemia in elderly or impaired patients, and/or they lack time or personnel resources to teach initiation. Strategies proposed to reduce PIR are educational and psychological (exposure, desensitisation, relaxation and counselling). We concluded that there is a great need of evidence-based interventions that help remove psychological barriers about insulin use in patients, as well as in health care providers. Copyright © 2011 John Wiley & Sons. Practical Diabetes Int 2011; 28(3): 125-128