Profile and factors associated with glycaemic control of patients with type 2 diabetes in Greece: results from the diabetes registry.

BACKGROUND: Strict glycaemic control early in the treatment process has been shown to reduce the occurrence of micro- and macro- vascular complications of diabetes in the long-term. Thus, treatment guidelines advise early intensification of treatment to achieve glycaemic control goals. However, evidence in Greece suggests that, despite guideline recommendations, glycaemic control among patients with T2DM remains challenging. This study presents the demographic and clinical characteristics of patients with T2DM in Greece using data from an electronic registry designed specifically for this treatment category and investigates the factors that are independently associated with glycaemic control. METHODS: This is a multi-center, observational, cross-sectional study to investigate epidemiological and clinical factors affecting glycaemic control among patients with T2DM in Greece. Data was collected via a web-based disease registry, the Diabetes Registry, which operated from January 1st to December 31st, 2017. Five large specialized diabetes centers operating in Greek hospitals participated in the study. RESULTS: Data for 1141 patients were retrieved (aged 63.02 ± 12.65 years, 56.9% male). Glycaemic control (Hb1Ac < 7%) was not achieved in 57.1% of patients. Factors independently associated with poor glycaemic control were: family history of diabetes [OR: 1.53, 95% CI: 1.06-2.23], BMI score between 25 to 30 [OR: 2.08, 95% CI: 1.05-4.13] or over 30 [OR: 2.12, 95% CI 1.12-4.07], elevated LDL levels [OR: 1.53, 95% 1.06-2.21] and low HDL levels [OR: 2.12, 95% CI: 1.44-3.12]. Lastly, use of injectable antidiabetic agents (in monotherapy or in combination) was less likely to be associated with poor glycaemic control versus treatment with combination of oral and injectable agents [OR: 0.50, 95% CI: 0.24-1.01]. This association was found to be marginally statistically significant. CONCLUSION: Inadequate lipid control, family history of diabetes and presence of obesity (ΒΜΙ ≥ 30 kg/m2) were associated with poor glycaemic control among study sample, whereas use of injectable antidiabetic agents was less likely to be associated with poor glycaemic control. These findings indicate how complex optimal glycaemic control is, highlighting the need for tailored interventions in high-risk subpopulations with T2DM.

The influence of gene polymorphisms on postprandial triglyceride response after oral fat tolerance test meal in patients with diabetes mellitus.

AIMS: We evaluated the influence of CETP (rs5882 and rs708272), APOE (rs7412, rs429358) and LPL (rs328) gene polymorphisms on triglyceride (TG) response to oral fat tolerance test (OFTT) meal in patients with well-controlled type 2 diabetes mellitus (T2DM). METHODS: Fifty-one men underwent OFTT and according to postprandial TG response patients were divided into two subgroups (positive [TG ≥ 220 mg/dL, 31 patients] and negative [TG < 220 mg/dL, 20 patients]). All patients were genotyped, and study variants were detected using polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) analysis. RESULTS: Patients with genotype SS of LPL gene compared with genotype SX had more frequently positive response to OFTT (P = .04) and lower high-density lipoprotein cholesterol (HDL-C) concentration (P = .03). Patients with positive response to OFTT and genotype SS of LPL gene compared with genotype SX had lower AUC (area under the curve)-TG, 1744 (368) vs 1887 (807) mg/dL/h, respectively, P = .04. CETP and APOE gene polymorphisms had no influence on postprandial TG response to OFTT. CONCLUSIONS: In patients with well-controlled T2DM, LPL but not CETP and APOE gene polymorphisms influenced TG postprandial response. Particularly, S447 allele carriers of LPL gene presented more frequently positive postprandial TG response to OFTT compared with 447X allele carriers. No differences were found between allele carriers of patients with negative response to OFTT in any other studied gene polymorphism.

Red blood cell distribution width as a prognostic marker in patients with heart failure and diabetes mellitus.

BACKGROUND: Red blood cell distribution width (RDW) is an established prognostic marker in acute and chronic heart failure (HF). Recent studies have pointed out a link among RDW, diabetes mellitus (DM) and inflammation. We sought to investigate the prognostic value and longitudinal pattern of RDW in patients with concomitant HF and DM, which remains unknown. METHODS: A total of 218 patients (71 diabetics) who presented with acute HF had RDW measured at admission, discharge and 4, 8 and 12 months post-discharge. The study endpoint was all-cause mortality or rehospitalization for HF during 1-year follow-up. RESULTS: The study endpoint was met in 33 patients (46.5%) with DM and in 54 patients (36.7%) without DM. RDW at admission was associated with higher event rate both in HF patients with and without DM (adjusted HR: 1.349, p = 0.002, 95% CI 1.120-1.624 and adjusted HR: 1.142, p = 0.033, 95% CI 1.011-1.291 respectively). In addition, a significant interaction was found between diabetes and RDW longitudinal changes (ßinteraction = -0.002; SE = 0.001; p = 0.042). CONCLUSIONS: Despite the similar prognostic significance of RDW in diabetic and non-diabetic HF patients regarding the study endpoint, longitudinal changes were found to be significantly different between these two groups of HF patients. This might be due to the higher inflammatory burden that diabetic HF patients carry and may provide new insights to the pathophysiological mechanism of RDW increase in HF, which remains unknown.

Management of type 2 diabetes and its prescription drug cost before and during the economic crisis in Greece: an observational study.

BACKGROUND: The aim of the present study is to examine the clinical indices related to cardiovascular risk management of Greek patients with type 2 diabetes, before and after the major economic crisis that emerged in the country. METHODS: In this retrospective database study, the medical records of patients with type 2 diabetes treated at three diabetes outpatient centers of the national health system during 2006 and 2012 were examined. Only patients with at least six months of follow-up prior to the recorded examination were included. The prescription cost was calculated in Euros per patient-year (€PY). RESULTS: A total of 1953 medical records (938 from 2006 and 1015 from 2012) were included. There were no significant differences in adjusted HbA1c, systolic blood pressure and HDL-C, while significant reductions were observed in LDL-C and triglycerides. In 2012, a higher proportion of patients were prescribed glucose-lowering, lipid-lowering and antihypertensive medications. Almost 4 out of 10 patients were prescribed the new incretin-based medications, while the use of older drugs, except for metformin, decreased. A significant increase in the adjusted glucose-lowering prescription cost (612.4 [586.5-638.2] €PY vs 390.7 [363.5-418.0]; p < 0.001) and total prescription cost (1306.7 [1264.6-1348.7] €PY vs 1122.3[1078.1-1166.5]; p < 0.001) was observed. The cost of antihypertensive prescriptions declined, while no difference was observed for lipid-lowering and antiplatelet agents. CONCLUSIONS: During the economic crisis, the cardiovascular risk indices of Greek patients with type 2 diabetes being followed in public outpatient diabetes clinics did not deteriorate and in the case of lipid profile improved. However, the total prescription cost increased, mainly due to the higher cost of glucose-lowering prescriptions.

Cost-effectiveness analysis of liraglutide versus sitagliptin or exenatide in patients with inadequately controlled Type 2 diabetes on oral antidiabetic drugs in Greece.

BACKGROUND: To evaluate the long-term cost-effectiveness of liraglutide versus sitagliptin or exenatide, added to oral antidiabetic drug mono- or combination therapy respectively, in patients with Type 2 diabetes in Greece. METHODS: The CORE Diabetes Model, a validated computer simulation model, was adapted to the Greek healthcare setting. Patient and intervention effects data were gathered from a clinical trial comparing liraglutide 1.2 mg once daily vs. sitagliptin 100 mg once daily, both combined with metformin, and a clinical trial comparing liraglutide 1.8 mg once daily vs. exenatide 10 µg twice daily, both as add-on to metformin, glimepiride or both. Direct costs were reported in 2013 Euros and calculated based on published and local sources. All future outcomes were discounted at 3.5% per annum, and the analysis was conducted from the perspective of a third-party payer in Greece. RESULTS: Over a patient's lifetime, treatment with liraglutide 1.2 mg vs. sitagliptin drove a mean increase in discounted life expectancy of 0.13 (SD 0.23) years and in discounted quality-adjusted life expectancy of 0.19 (0.16) quality-adjusted life years (QALYs), whereas therapy with liraglutide 1.8 mg vs. exenatide yielded increases of 0.14 (0.23) years and 0.19 (0.16) QALYs respectively. As regards lifetime direct costs, liraglutide 1.2 mg resulted in greater costs of €2797 (€1468) versus sitagliptin, and so did liraglutide 1.8 mg compared with exenatide (€1302 [€1492]). Liraglutide 1.2 and 1.8 mg doses were associated with incremental cost effectiveness ratios of €15101 and €6818 per QALY gained, respectively. CONCLUSIONS: Liraglutide is likely to be a cost-effective option for the treatment of Type 2 diabetes in a Greek setting.

Manuka honey-impregnated dressings in the treatment of neuropathic diabetic foot ulcers.

In this study, we investigate the effect of manuka honey-impregnated dressings (MHID) on the healing of neuropathic diabetic foot ulcers (NDFU). A total of 63 Caucasians, type 2 diabetic patients followed up in the diabetic foot outpatient clinic comprised the study population. Patients were randomised in two groups as follows: group I patients were treated with MHID and group II patients were treated with conventional dressings (CD). The patients were followed up on a weekly basis for 16 weeks. Mean healing time was 31 ± 4 days in group I versus 43 ± 3 days in group II (P < 0·05). In group I patients 78·13% of ulcers became sterile during the first week versus 35·5% in group II patients; the corresponding percentages for weeks 2, 4 and 6 were 15·62% versus 38·7%, 6·25% versus 12·9% and 0% versus 12·9% respectively. The percent of ulcers healed did not differ significantly between groups (97% for MHID and 90% for CD). MHID represent an effective treatment for NDFU leading to a significant reduction in the time of healing and rapid disinfection of ulcers.

Evaluation of IScore validity in a Greek cohort of patients with type 2 diabetes.

BACKGROUND: Diabetes constitutes a risk factor for stroke that also aggravates stroke prognosis. Several prognostic models have been developed for the evaluation of neurologic status, severity, short-term functional outcome and mortality of stroke patients. IScore is a novel tool recently developed in order to predict mortality rates within 30 days and 1 year after ischemic stroke and diabetes is not included in the scoring scale of IScore. The aim of the present study was to evaluate and compare IScore validity in ischemic stroke patients with and without diabetes. METHODS: This prospective study included 312 consecutive Caucasian patients with type 2 diabetes and 222 Caucasian patients without diabetes admitted for ischemic stroke in a tertiary Greek hospital. Thirty-day and 1-year IScores were individually calculated for each patient and actual mortality was monitored at the same time intervals. IScore's predictive ability and calibration was evaluated and compared for ischemic stroke patients with and without diabetes. The performance of IScore for predicting 30 and 1-year mortality between patients with and without diabetes was assessed by determining the calibration and discrimination of the score. The area under the receiver operating characteristic curve was used to evaluate the discriminative ability of IScore for patients with and without diabetes, whereas the calibration of IScore was assessed by the Hosmer-Lemeshow goodness-of fit statistic. RESULTS: Baseline population characteristics and mortality rates did not differ significantly for both cohorts. IScore values were significantly higher for patients with diabetes at 30 days and 1 year after ischemic stroke and patients with diabetes presented more frequently with lacunar strokes. Based on ROC curves analysis IScore's predictive ability for 30 day mortality was excellent, without statistically significant difference, for both cohorts. Predictive ability for 1 year mortality was also excellent for both groups with significantly better ability for patients with diabetes especially at high score values. Calibration of the model was good for both groups of patients. CONCLUSIONS: IScore accurately predicts mortality in acute ischemic stroke Caucasian patients with and without diabetes with higher efficacy in predicting 1 year mortality in patients with diabetes especially with high scores.

Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk factors on pulse wave velocity among prediabetic individuals.

BACKGROUND: Central arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study. METHODS: The study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined. RESULTS: Among studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise. CONCLUSIONS: Elevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.

Antiplatelet and Antithrombotic Therapy in Type I Diabetes Mellitus: Update on Current Data.

Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors. The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.

Toll/interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction.

BACKGROUND: Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c. METHODS: 158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction<50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis). RESULTS: Patients with type 2 diabetes with (p<0.001) or without LVDD (p=0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p=0.213 & p=0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p=0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes. CONCLUSIONS: Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.

Anemia and early mortality in patients with decompensation of chronic heart failure.

OBJECTIVES: The possible independent effect of mild-to-moderate anemia (hemoglobin value not <9 g/dl) on the short-term mortality of patients with decompensation of NYHA class III/IV chronic heart failure has not been investigated yet. METHODS: A total of 725 consecutive hospitalized patients were studied. All-cause mortalities during hospitalization and by day 31 were the prespecified study end points. RESULTS: A total of 76 (10.5%) and 133 (18.3%) patients died during hospital stay and by day 31 of follow-up, respectively. Patients in the first hemoglobin tertile were at a significantly higher risk of death than those in the second (p = 0.003 and p < 0.001 for unadjusted in-hospital and 31-day mortality, respectively) or third terile (p < 0.001 and p < 0.001, for unadjusted in-hospital and 31-day mortality, respectively). However, after adjustment for concomitant baseline comorbidities and biochemical parameters, there was no significant difference in the risk of death among hemoglobin tertiles. CONCLUSIONS: Mild-to-moderate anemia seems not to contribute independently to short-term mortality in patients with decompensation of NYHA class III/IV chronic heart failure. An adverse concomitant baseline risk profile may have a key role in the induction of mild-to-moderate anemia and in the increased risk of death in these patients.

Aspirin in primary prevention of cardiovascular disease in diabetes.

It is well established that people with diabetes are at an increased risk of cardiovascular disease compared with those without diabetes. Although the protective role of aspirin in secondary prevention is well documented, its role in primary prevention of cardiovascular disease in people with diabetes, after the results of major clinical trials and meta-analyses, is unclear. The observed discrepancies might be explained in part in terms of the differences between the background cardiovascular risks, follow-up periods, age and gender of the study populations. Recently, the results of the ASCEND trial in people with diabetes documented the cardiovascular benefit of aspirin for primary prevention, but with an increased risk of bleeding that might outweigh the observed cardiovascular benefit. Therefore, current guidelines recommend its use for primary prevention in people with and without diabetes under specific circumstances. The purpose of the present review is to summarize the existing literature data regarding the place that aspirin has in primary prevention of cardiovascular disease in people with diabetes.

Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes.

During the last decade, the results of large-scale, randomized, clinical trials on newer antidiabetic agents, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter type 2 (SGLT2) inhibitor, have been published showing promising findings on cardiovascular and renal outcomes. Besides improving glycemic control, GLP-1 receptor agonists have been shown to modify cardiovascular risk factors, such as insulin resistance, body weight, blood pressure (BP), and lipid profile. Additionally, SGLT2 inhibitors except for glycemic control have been shown to induce weight loss and decrease BP. However, there are limited data regarding their effect on patients without diabetes. Therefore, the aim of the present review is to summarize the existing literature data regarding the effects of newer antidiabetic therapies on patients without diabetes.

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study.

AIM: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). PATIENTS AND METHODS: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. RESULTS: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. CONCLUSIONS: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.

Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events.

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; P=0.809). Conclusions Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.

Heart rate variability in advanced chronic kidney disease with or without diabetes: midterm effects of the initiation of chronic haemodialysis therapy.

BACKGROUND: Previous studies in different clinical settings have established heart rate variability (HRV) as a significant independent risk factor for higher mortality and cardiac death. The aim of this study was to examine the effect of chronic haemodialysis therapy on time- and frequency-domain parameters of HRV in diabetic and non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 25 patients with stage 4 CKD and type 2 diabetes mellitus (CKD4+DM), 25 patients with stage 4 CKD without diabetes (CKD4), 25 patients with type 2 diabetes mellitus (DM) and 25 healthy subjects (HS). The study was performed in two phases. In the first phase, a 24-h Holter electrocardiographic (ECG) monitoring was performed in all subjects. The patients with stage 4 CKD were followed up until they progressed to stage 5, and in the second phase of the study, they underwent a 24-h Holter ECG monitoring after completion of 3 months of conventional haemodialysis treatment. RESULTS: In the first phase of the study, a reduction in cardiac sympathetic activity in CKD4 patients (significantly lower SDNN, SDANN/5 min, SD and VLF vs. HS) and worse autonomic function in CKD4+DM patients (significantly lower SDNN, SDANN/5 min, SD, VLF and LF/HF) vs. HS, DM and CKD4 was observed. After 3 months of dialysis therapy, the patients with CKD+DM showed a significant improvement only in the time-domain parameter SDANN/5 min, while the time-domain parameters SDNN, SDANN/5 min and SD were improved in CKD patients without diabetes. Frequency-domain parameters of HRV remained unchanged in both groups. CONCLUSIONS: CKD is associated with worse cardiac autonomic function. Haemodialysis therapy for 3 months improves some indices of HRV, and this effect is more pronounced in non-diabetic subjects. Our findings suggest that the improvement of HRV after the initiation of chronic dialysis therapy can ameliorate clinical outcomes and survival in patients with end-stage renal disease.

Diabetes and dementia - the two faces of Janus.

Patients with type 2 diabetes are at high risk for cognitive decline and dementia. Despite the limited data on the possible pathogenetic mechanisms, evidence suggests that cognitive decline, and thus dementia and Alzheimer's disease, might arise from a complex interplay between type 2 diabetes and the aging brain, including decreased insulin signalling and glucose metabolism, mitochondrial dysfunction, neuroinflammation, and vascular disease. Furthermore, there is increasing interest on the effects of antidiabetic agents on cognitive decline. There are many studies showing that antidiabetic agents might have beneficial effects on the brain, mainly through inhibition of oxidative stress, inflammation, and apoptosis. In addition, experimental studies on patients with diabetes and Alzheimer's disease have shown beneficial effects on synaptic plasticity, metabolism of amyloid-ß, and microtubule-associated protein tau. Therefore, in the present review, we discuss the effects of antidiabetic agents in relation to cognitive decline, and in particular dementia and Alzheimer's disease, in patients with type 2 diabetes.

Clinical Management of Diabetes Mellitus in the Era of COVID-19: Practical Issues, Peculiarities and Concerns.

The management of patients with diabetes mellitus (DM) in the era of the COVID-19 pandemic can be challenging. Even if they are not infected, they are at risk of dysregulated glycemic control due to the restrictive measures which compromise and disrupt healthcare delivery. In the case of infection, people with DM have an increased risk of developing severe complications. The major principles of optimal care for mild outpatient cases include a patient-tailored therapeutic approach, regular glucose monitoring and adherence to medical recommendations regarding lifestyle measures and drug treatment. For critically ill hospitalized patients, tight monitoring of glucose, fluids, electrolytes, pH and blood ketones is of paramount importance to optimize outcomes. All patients with DM do not have an equally increased risk for severity and mortality due to COVID-19. Certain clinical and biological characteristics determine high-risk phenotypes within the DM population and such prognostic markers need to be characterized in future studies. Further research is needed to examine which subgroups of DM patients are expected to benefit the most from specific antiviral, immunomodulatory and other treatment strategies in the context of patient-tailored precision medicine, which emerges as an urgent priority in the era of COVID-19.

Twenty-year trends in the prescription costs of Type 2 diabetes: Real world data and empirical analysis in Greece.

AIMS: To estimate and compare the prescription costs for the management of patients with diabetes over a period of 20 years in Greece, based on real world data. METHODS: The records of outpatients with T2D, monitored at three diabetes centres, were examined in four cross-sections (1998, 2006, 2012, 2018). Prescribed medicines per patient, along with a set of clinical indicators were recorded. Annual costs of pharmaceutical treatment per patient were calculated by using each year's nominal retail prices, as well as by adjusting for 2018 price levels, in order to account for price differences over time. RESULTS: 4066 patients were included in the analysis. Prescription patterns indicate a quick uptake of the new classes of glucose-lowering drugs and a reduction in the proportional use of sulfonylurea and glitazone. Adjusting for 2018 prices, the average total annual prescription cost per patient was 381.54 Euros (s.d. 297.44) in 1998 and 1147.21 Euros (s.d. 814.39) in 2018. Glucose-lowering drug costs per patient increase from 1998 onwards, whereas the costs of antihypertensive, antiplatelet and lipid-lowering treatment declined gradually, especially after 2006. CONCLUSIONS: Per patient prescription costs for glucose-lowering drugs present a steep increase, in Greece over the last 20 years. Real-world evidence studies that compare this increase with the changes in patient outcomes are essential in order to examine whether a costs-vs-outcomes balance is optimal.

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

INTRODUCTION: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA1c), blood pressure and lipid control achievement rates in the routine care setting in Greece. METHODS: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA1c measurements in the previous year and an HbA1c target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year. RESULTS: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA1c, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively. CONCLUSIONS: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.