Prevalence of Metabolic X Syndrome in the Interior of Croatia: The Baranja Region

Metabolic syndrome (MS), a constellation of metabolic risk factors associated with development of cardiovascular diseases and type 2 diabetes, has emerged as a public health problem of enormous proportions in developed and developing countries. We have reported previously its prevalence in several isolated island populations in the Eastern Adriatic coast of Croatia. In spite of leading a relatively traditional life style pattern including the practice of a typical Mediterranean diet, the prevalence of MS in these populations is high and comparable to those in developed nations. However, data on prevalence of the syndrome in mainland Croatia is limited. We have, therefore, conducted a study in an outbred population comprising of Croats, Hungarians and Serbs from the Baranja region of mainland Croatia. Although this is an ethnically heterogenous population, the constituent groups exchange mates and therefore, are not reproductively isolated. The life style patterns are also similar. We observed similar prevalence of MS in these groups. We assessed MS following the definitions prescribed in the guidelines of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP). Overall prevalence is considerably high in this cosmopolitan group, by WHO criteria 26% in males and 38% in females, and by NCEP criteria 84% in males and 71% in females. It is likely that, in addition to genetic risk factors, a host of environmental factors that include dietary habit and relatively urban life style in a modernized society influence the levels of the constituent metabolic traits leading to increase prevalence of MS

Pharmacological Treatment of Osteoporosis: An Update

Osteoporoza (OP) je kronična bolest kostiju koju karakterizira poremećena mikrostruktura koštane građe što vodi do smanjene koštane mase i povećanog rizika od prijeloma. Antiresorptivni lijekovi, posebice bisfosfonati, trenutno su prvi izbor u liječenju osteoporoze u većini zemalja. Međutim, oni imaju svoja ograničenja, što je potaknulo razvitak osteoanaboličkih lijekova kao što su teriparatid i romosozumab, no i oni imaju svoje štetne učinke. Ipak, neosporno je da korist lijekova za osteoporozu nadvladava potencijalne rizike. U bolesnika s visokim ili vrlo visokim rizikom od prijeloma mogu se razmotriti sekvencijalne ili kombinirane terapije s anaboličkim agensom kao početnim lijekom. S obzirom na rastuću prevalenciju osteoporoze ulažu se veliki napori kako bi se razvili lijekovi sljedeće generacije s maksimalnom učinkovitosti i što prihvatljivijim sigurnosnim profilom. U postizanju ovoga cilja potrebno je što bolje razumijevanje uloga različitih signalnih putova u patogenezi osteoporoze. Najveći napori uloženi su u razvitak lijekova koji utječu na modifikaciju Wnt signalnog puta koji mogu imati i antiresorptivno i/ili osteoanaboličko djelovanje ovisno na koju etapu, odnosno signalnu molekulu djelujemo.Osteoporosis (OP) is a chronic bone disease characterized by disturbed bone microarchitecture, which leads to reduced bone mass and increased risk of fractures. Antiresorptive drugs, especially bisphosphonates, are currently the first choice in the treatment of osteoporosis in most countries. However, their limitations prompted the development of osteoanabolic drugs such as teriparatide and romosozumab, with their own adverse effects. Still, it is undeniable that the benefits of antiosteoporosis drugs outweigh the potential risks. In patients at high or very high fracture risk, sequential or combination therapies with an anabolic agent as an initial agent may be considered. Due to the growing prevalence of osteoporosis, great efforts are being made to develop next-generation drugs with maximum effectiveness and an acceptable safety profile. Achieving this goal requires a better insight in different signaling pathways involved in the pathogenesis of osteoporosis. The greatest efforts have been made in the development of drugs that affect the modification of the Wnt signaling pathway, which can have anti-resorptive and/or osteoanabolic effects depending on the target signaling molecule

Hepatitis C Virus, Insulin Resistance, and Steatosis

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality

Long-term Effectiveness of Liraglutide in Association with Patients' Baseline Characteristics in Real-life Setting in Croatia: an Observational, Retrospective, Multicenter Study

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are recommended therapy for type 2 diabetes (T2DM) and liraglutide is the most used worldwide. We assessed the glycemic efficacy and extra-glycemic effects of liraglutide during 36 months' follow-up of individuals with poorly regulated T2DM under routine clinical practice and sought to identify the phenotype of treatment responders. METHODS: A total of 207 individuals were included. The primary endpoint was the proportion of participants with HbA1c < 7.0% and/or weight reduction. Secondary endpoints included changes in lipids, blood pressure, fasting c-peptide, and antidiabetic treatment during follow-up of 3 years. RESULTS: Liraglutide was prescribed to 89.8% of participants already on at least two antidiabetic medications and 18% on insulin. Subject's mean age was 53.28 ± 9.42 years with duration of diabetes 8.29 ± 4.89 years. Baseline HbA1c was 8.5 ± 1.3% and body mass index (BMI) was 39 ± 4.5 kg/m2. Reduction of HbA1c was observed in 84.4% of participants, and 89.2% experienced average weight reduction of 5 kg. A composite outcome (reduction of HbA1c with any weight loss) was achieved in 76.2% of patients. After 6 months on liraglutide treatment, 38.1% of participants achieved target HbA1c level < 7%. This effect was maintained for 36 months in 50.8% of subjects. Increase in c-peptide was evident after 24 months (p = 0.030). Participants experienced a significant reduction in systolic blood pressure (BP) (p = 0.003), while there was no effect on diastolic BP, lipid profile, or liver enzymes. The number of participants treated with sulfonylurea decreased from 60.8% to 17.5%, while the number treated with insulin and sodium-glucose co-transporter-2 (SGLT-2) inhibitor increased (17.6% to 24.6% and 2.5% to 36.8%, respectively). Independent predictors of durability of HbA1c reduction were initial BMI (p = 0.004), HbA1c (p < 0.001), systolic BP (p = 0.007), and cholesterol (p = 0.020). Moreover, female gender and shorter duration of diabetes were independent predictors for HbA1c reduction. CONCLUSION: Liraglutide shows sustained glycemic and extra-glycemic effects when used for treatment of obese poorly regulated individuals with T2DM

Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

ACKGROUND The sodium/glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like-1 receptor agonists (GLP-1RA) are antidiabetic agents effective both in hemoglobin A1c (HbA1c) reduction (with a low risk of hypoglycemia) and cardiovascular event prevention. In patients with type 2 diabetes, the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising. AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up. METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with (1) GLP-1RA on top of SGLT-2i, (2) SGLT-2i on top of GLP-1RA compared to (3) simultaneous addition of both agents. The primary study endpoint was the proportion of participants with HbA1c < 7.0% and/or 5% bodyweight reduction. Secondary outcomes included changes in fasting plasma glucose (FPG), prandial plasma glucose, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and cardiovascular (CV) incidents assessment over a follow-up period of 12 mo. RESULTS The majority of patients were over 65-years-old, had diabetes duration for more than 10 years. The initial body mass index was 39.41 ± 5.49 kg/m2 and HbA1c 8.32 ± 1.26%. Around half of the patients in all three groups achieved target HbA1c below 7%. A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy. The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group (P = 0.021), and 5% weight loss was dominantly achieved in the simultaneous therapy group (P = 0.044). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with 5% weight loss) was achieved in 32.3% of total patients included in the study. Only 18.2% of patients attained composite outcome defined as HbA1c below 7% (53 mmol/mol) with 5% weight loss and low-density lipoprotein cholesterol < 2.5 mmol/L. There were no significant differences between treatment groups. No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period. CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control, although it remains to be determined whether simultaneous or sequential intensification is better

Assessment of FreeStyle Libre Flash Glucose Monitoring System Implementation in Real Life Clinical Setting: A Prospective Observational Study

Background: In this study, we investigated the effectiveness of FreeStyle Libre Flash Glucose Monitoring (FGM) implementation in a real life clinical setting with the emphasis on the effect of initial education on the use of the FGM system. Methods: This prospective observational study included 425 diabetes type 1 subjects followed up for 3 to 12 months (320 were followed up to 3 months, 267 up to 6 months and 147 up to period of one year). An FGM sensor was placed at study entry and all participants were educated through a period of 5 days on sensor usage and self-management of glycemia with follow up visits every 3 months. Results: HbA1c values significantly decreased from baseline (T0) to 3 months (T3) (p < 0.001), with a drop from 7.48% ± 0.1% to 7.30 ± 0.1%. There was no change in time spent in hypoglycemia from T3 to T12, although there was a decreasing trend present. The change in HbA1c values in the entire cohort was driven by change in the subgroup of patients with HbA1c ≥7% with a drop from 8.22% ± 1.14% to 7.68% ± 1.26% (p < 0.0001) in the first 3 months. Also, in individuals performing SMBG less than 5 times per day, there was a steady decrease in HbA1c levels up to 6 months (p < 0.05 and p < 0.001, respectively) as opposed to those who performed SMBG ≥5 times per day. Conclusions: The improvement in HbA1c was mainly driven by the increase in the number of scans per day. The subjects with poorer glycemic control and those who seldom performed SMBG benefited the most

Prevalence of metabolic syndrome in the interior of Croatia: the Baranja region

Metabolic syndrome (MS), a constellation of metabolic risk factors associated with development of cardiovascular diseases and Type 2 diabetes (T2D), has emerged as a public health problem of enormous proportions in developed and developing countries. We have reported previously its prevalence in several island populations of the Eastern Adriatic coast of Croatia. In spite of leading a relatively traditional life style pattern including adherence to a Mediterranean diet, the prevalence of MS in these populations is high and comparable to that in developed nations. However, data on prevalence of MS among the mainland Croatian populations is limited. Therefore, we conducted a study in an outbred population comprising of Croats, Hungarians and Serbs from the Baranja region of mainland Croatia. Although this is an ethnically heterogeneous population, the constituent groups exchange mates and therefore, are not reproductively isolated. The life style patterns are also similar. Overall prevalence of MS, assessed by the National Cholesterol Education Program (NCEP) criteria, is 40% (35% in males and 42% in females) with Body Mass Index (BMI) as the predictor of obesity and 42% (52% in males and 39% in females) with Waist Hip Ratio (WHR) as the predictor of obesity. It is likely that, in addition to genetic risk factors, a host of environmental factors that include dietary habits and relatively urban life style in a modernized society have influenced the levels of the constituent metabolic traits leading to an increased prevalence of MS