Impact of SGLT2 inhibitors on the mechanisms of myocardial dysfunction in type 2 diabetes: A prospective non-randomized observational study in patients with type 2 diabetes mellitus without overt heart disease.

AIMS: This prospective observational study evaluated the possible mechanisms of action of SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) without overt heart disease. METHODS: The study was designed to verify whether SGLT2i impact biomarkers of: myocardial stress-NT-proBNP, inflammation-high sensitivity C-reactive protein, oxidative stress -myeloperoxidase, functional and structural echocardiographic parameters, in patients with T2DM on metformin (heart failure stages A and B) who needed treatment intensification with a second antidiabetic agent. The patients were divided in two groups - the ones planned to receive SGLT2i or DPP-4 inhibitor (except saxagliptin). At baseline, and after six months of therapy, 64 patients underwent blood analysis, physical and echocardiography examination. RESULTS: There were no significant differences between the two groups in terms of biomarkers of myocyte and oxidative stress, inflammation and blood pressure. Body mass index, triglycerides, aspartate aminotransferase, uric acid, E/E', deceleration time and systolic pressure in the pulmonary artery significantly decreased, while stroke volume, indexed stroke volume, high-density lipoprotein, hematocrit and hemoglobin significantly increased in the group on SGLT2i. CONCLUSIONS: According to the results, SGLT2i mechanisms of action comprise rapid changes in body composition and metabolic parameters, reduced cardiac load and improvement in diastolic and systolic parameters.

Prediabetes, Non-Dipping Profile and Hypertension-A Recipe for Increased Arterial Stiffness.

BACKGROUND: Pulse wave velocity (PWV) is a known predictor of target organ damage, cardiovascular disease and overall mortality. The aim of this study was to compare the PWV values in subjects with prediabetes, a non-dipper profile and arterial hypertension with their values in healthy subjects. METHODS: A total of 301 subjects, aged 40-70 years, without diabetes mellitus were included in this cross-sectional study (150 with prediabetes). They underwent a 24 h ambulatory blood pressure monitoring (ABPM). Subjects were divided into three hypertension groups (A = healthy, B = controlled hypertension, C = uncontrolled hypertension). Dipping status was determined according to ABPM results, and PWV was measured by an oscillometric device. Prediabetes was defined as having 2 separate fasting plasma glucose (FPG) measurements between 5.6 and 6.9 mmol/L. RESULTS: The highest PWV values were found in group C (9.60 ± 1.34 vs. 8.46 ± 1.01 in group B vs. 7.79 ± 1.10 in group A; p < 0.001), in subjects with prediabetes (8.98 ± 1.31 m/s vs. 8.26 ± 1.22 m/s; p < 0.001) and in prediabetic non-dippers among age groups (p = 0.05). In the multivariate regression model age, blood pressure, nocturnal indices and FPG were shown as independent predictors of PWV values. CONCLUSION: Significantly higher PWV values were found in subjects with prediabetes and non-dipping profiles in all three examined hypertension groups.

Point-of-care testing, antibiotic prescribing, and prescribing confidence for respiratory tract infections in primary care: a prospective audit in 18 European countries.

BACKGROUND: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. AIM: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs' prescribing confidence. DESIGN & SETTING: Prospective audit in 18 European countries. METHOD: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. RESULTS: Antibiotic prescribing proportions varied considerably: <20% in four countries, and >40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (<3% in Hungary, the Netherlands, and Spain, and >30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. CONCLUSION: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.

NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms.

Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms PNPLA3 rs738409, EGF rs4444903, TM6SF2 rs58542926, MTHFR rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms (NOTCH1 rs3124591, NOTCH3 rs1043996 and rs1044116, NOTCH4 rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients' susceptibility to ALC was significantly associated with PNPLA3 rs738409, TM6SF2 rs58542926, and NOTCH3 rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the PNPLA3 GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with PNPLA3 rs738409 and EGF rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors.

Croatian diabetes registry (CroDiab) and implementation of standardised diabetes checklists using Joint Action CHRODIS Recommendations and Criteria.

INTRODUCTION: Standardized diabetes monitoring checklists is an efficient registry collection tool and diabetes care improvement aid. Aim of this study was to improve the management of diabetes according to international standards and based on Joint Action CHRODIS Recommendations and Criteria, and to improve general practitioners (GPs) awareness of importance of monitoring via diabetes checklists. POPULATION AND METHODS: Twenty-eight GPs and 1242 diabetic patients were included. GPs were divided in groups regarding the intensity of education and information provided. Quantitative analyses of diabetes quality indicators and their availability as well as qualitative study in intensive group were performed. RESULTS: Average number of patients with fulfilled checklists per GP increased from 20.2 to 30.8 (52.30%). Most GPs had positive attitude towards checklists but there is still a room for further improvement. DISCUSSION AND CONCLUSIONS: Checklists are perceived as positive initiatives by GPs; however, there are areas for further improvements. General practitioners education and feedback regarding the checklists may contribute to better monitoring of patients with diabetes.

Awareness, attitudes, barriers, and knowledge about evidence-based medicine among family physicians in Croatia: a cross-sectional study.

BACKGROUND: Evidence-based medicine (EBM) aims to assist physicians in making medical decisions based on the integration of the current best evidence, clinical expertise, and patients' values. Extensive research has been conducted regarding physicians' awareness, attitudes, barriers, and knowledge about EBM. In Croatia, there is a lack of research on this topic, especially among family physicians (FP). The aim of this study was to assess the awareness, attitudes, barriers, and knowledge about EBM among FPs in Croatia after six years of educational activities organized and provided by Cochrane Croatia. METHODS: In a cross-sectional study, conducted in 2016, we offered to FPs in Croatia a printed or online validated questionnaire to assess attitudes toward and barriers when considering the use of EBM, awareness about sources of evidence, and their level of understanding of evidence-based medicine terminology. The physicians were approached during mandatory continuing medical education courses and through their professional associations. We compared results from two groups of physicians, one with family medicine specialization and the other without. RESULTS: 295 (14%) of all officially registered FPs responded to the questionnaire. Respondents were very positive toward the promotion and usage of EBM. 160 (67%) indicated that they did not have access to the Cochrane Library. The majority reported lack of time available for finding evidence (80%), and patients' unrealistic expectations that influence doctors' choice of treatment (72%). Between the two groups of physicians, more family medicine specialists reported time restrictions for finding evidence. The highest level of EBM terminology understanding was reported for study design terms, and the lowest for statistical terms. CONCLUSIONS: This study demonstrated that FPs in Croatia had very positive attitudes toward the use of EBM, they agreed that EBM improves patient care, and they estimated that more than two thirds of their practice is EBM-based. Compared to the results of the first assessment of physicians in 2010, there was some increase in the level of EBM awareness among FPs. However, to further increase the quality of EBM practice in Croatia better access to EBM sources and further educational activities are needed.

Total and partial clinical inertia of general physicians with type 2 diabetes mellitus patients in Central Bosnia Canton.

BACKGROUND: The goal of this study was to determine the frequency and predictive factors of partial (PCI) and total clinical inertia (TCI) of general physicians (GPs) in Central Bosnia Canton in the care of type 2 diabetes mellitus patients. MATERIAL AND METHODS: A longitudinal study was conducted with a prospective data collection. Total of 541 subjects of over 40 years of age with type 2 diabetes mellitus of both genders were included in the study. Total of 532 subjects completed the study. Questionnaires for physicians and patients and the Perceived Stress Scale were used, as well as anthropometric measurements and measurements of the glucose level in plasma, HbA1c, triglycerides, AST, ALT, creatinine and eGFR, which were examined on the day of study entry, after 6 months and after one year. RESULTS: TCI was 5.8% and PCI was 25.6%. Patients with poorly regulated glycaemia and elevated triglyceride levels had the highest probability of PCI and TCI. Patients with an unaccomplished targeted level of blood pressure were more likely to experience PCI. Patients treated by both an internist and a general physician were more likely to have TCI as compared to patients treated only by an internist. CONCLUSIONS: Patients with poor glycemic control experience PCI and TCI more often. In our study, referring to a diabetologist was observed as a non-inert procedure, which resulted in lower PCI and TCI, compared to studies where clinical inertia was defined only as non-intensification of medication therapy.

Clinical Inertia in Type 2 Diabetes Patients in Primary Health Care Clinics in Central Bosnia.

BACKGROUND The goal of this research was to determine the frequency of clinical inertia of general practice physicians in the region of Central Bosnia in healthcare for type 2 diabetes patients, to analyze characteristics of patients and physicians, as well as glucose regulation during clinical inertia, and, on the basis of these indicators, give recommendations for reducing clinical inertia. MATERIAL AND METHODS This study included 29 doctors, family physicians, or general practitioners, who collected data in a total sample of 541 type 2 diabetes mellitus patients from July to November 2017. The research was conducted using 2 questionnaires. The glucose concentration in plasma and the percentage of glycosylated hemoglobin (HbA1c) were determined. Concertation of cholesterol, triglycerides, AST, and ALT were also measured. After the collection, new data were processed and the degree of clinical inertia was determined. RESULTS Levels of HbA1c ranged from 4.3% to 13.0%, and 38.4% of all patients had HbA1c level higher than 7.5%, while 8.3% of them had HbA1c level 9.0% or higher. Clinical inertia in our research was 12.6% out of all patients and 48.2% were referred to a specialist by their doctor. CONCLUSIONS For better regulation of glycemia and reduction of clinical inertia with type 2 diabetes patients, more specialized training is needed for selected physicians. Strengthening of primary healthcare and encouraging doctors to perform procedures can contribute to better outcomes of treatment, lower clinical inertia, and better education of patients.

Prevalence of comorbidity in primary care patients with type 2 diabetes and its association with elevated HbA1c: A cross-sectional study in Croatia.

OBJECTIVE: To the authors' knowledge, there are few valid data that describe the prevalence of comorbidity in type 2 diabetes mellitus (T2DM) patients seen in family practice. This study aimed to investigate the prevalence of comorbidities and their association with elevated (≥ 7.0%) haemoglobin A1c (HbA1c) using a large sample of T2DM patients from primary care practices. DESIGN: A cross-sectional study in which multivariate logistic regression was applied to explore the association of comorbidities with elevated HbA1c. SETTING: Primary care practices in Croatia. SUBJECTS: Altogether, 10 264 patients with diabetes in 449 practices. MAIN OUTCOME MEASURES: Comorbidities and elevated HbA1c. RESULTS: In total 7979 (77.7%) participants had comorbidity. The mean number of comorbidities was 1.6 (SD 1.28). Diseases of the circulatory system were the most common (7157, 69.7%), followed by endocrine and metabolic diseases (3093, 30.1%), and diseases of the musculoskeletal system and connective tissue (1437, 14.0%). After adjustment for age and sex, the number of comorbidities was significantly associated with HbA1c. The higher the number of comorbidities, the lower the HbA1c. The prevalence of physicians' inertia was statistically significantly and negatively associated with the number of comorbidities (Mann-Whitney U test, Z = -12.34; p < 0.001; r = -0.12). CONCLUSION: There is a high prevalence of comorbidity among T2DM patients in primary care. A negative association of number of comorbidities and HbA1c is probably moderated by physicians' inertia in treatment of T2DM strictly according to guidelines. KEY POINTS: There is a high prevalence of comorbidity among T2DM patients in primary care. Patients with breast cancer, obese patients, and those with dyslipidaemia and ischaemic heart disease were more likely to have increased HbA1c. The higher the number of comorbidities, the lower the HbA1c.

The association of lifestyle and stress with poor glycemic control in patients with diabetes mellitus type 2: a Croatian nationwide primary care cross-sectional study.

AIM: To assess lifestyle habits and self-reported stress levels among type 2 diabetes mellitus (T2DM) patients and their association with hemoglobin A1c (HbA1c) in general practitioners' (GP) offices in Croatia. METHODS: 449 GPs from all Croatian regions from 2008 to 2010 consecutively recruited up to 20-25 participants diagnosed with T2DM at least 3 years prior to the study, aged ≥40 years, and scheduled for diabetes control check-ups. The recruitment period lasted six months. Lifestyle habits and self-reported stress were assessed using the questionnaire from the Croatian Adult Health Survey. RESULTS: The study included 10285 patients with T2DM with mean (±standard deviation) age of 65.7±10.05 years (48.1% men). Mean HbA1c level was 7.57±1.58%. 79% of participants reported insufficient physical activity, 24% reported inappropriate dietary patterns, 56% reported current alcohol consumption, 19% were current smokers, and 85% reported at least medium level of stress. Multivariate analysis showed that having received advice to stop drinking alcohol, inadequate physical activity, consumption of milk and dairy products, adding extra salt, and high level of stress were significantly associated with increased HbA1c (P < 0.05). CONCLUSION: Poor glycemic control was more frequent in patients who had several "unhealthy" lifestyle habits. These results suggest that diabetes patients in Croatia require more specific recommendations on diet, smoking cessation, exercise, and stress control.

Family physician clinical inertia in glycemic control among patients with type 2 diabetes.

BACKGROUND: Many patients with diabetes do not achieve target values. One of the reasons for this is clinical inertia. The correct explanation of clinical inertia requires a conjunction of patient with physician and health care system factors. Our aim was to determine the rate of clinical inertia in treating diabetes in primary care and association of patient, physician, and health care setting factors with clinical inertia. MATERIAL AND METHODS: This was a national, multicenter, observational, cross-sectional study in primary care in Croatia. Each family physician (FP) provided professional data and collected clinical data on 15-25 type 2 diabetes (T2DM) patients. Clinical inertia was defined as a consultation in which treatment change based on glycated hemoglobin (HbA1c) levels was indicated but did not occur. RESULTS: A total of 449 FPs (response rate 89.8%) collected data on 10275 patients. Mean clinical inertia per FP was 55.6% (SD ±26.17) of consultations. All of the FPs were clinically inert with some patients, and 9% of the FPs were clinically inert with all patients. The main factors associated with clinical inertia were: higher percentage of HbA1c, oral anti-diabetic drug initiated by diabetologist, increased postprandial glycemia and total cholesterol, physical inactivity of patient, and administration of drugs other than oral antidiabetics. CONCLUSIONS: Clinical inertia in treating patients with T2DM is a serious problem. Patients with worse glycemic control and those whose therapy was initiated by a diabetologist experience more clinical inertia. More research on causes of clinical inertia in treating patients with T2DM should be conducted to help achieve more effective diabetes control.