The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D ...who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium-glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the use of statins, familial hypercholesterolemia (FH) patients often have increased LDL-cholesterol (Ch) and high risk for atherosclerotic cardiovascular disease (ASCVD). This study aimed to ...analyze the effect of statin therapy on attainment of LDL-Ch treatment targets and appearance of new ASCVD and diabetes in FH patients.
This study is a retrospective analysis of data from medical records of 302 FH patients treated continuously with statins during 3 years. At baseline and once yearly, anthropometric measurements, lipids (total Ch, LDL-Ch, HDL-Ch, triglycerides, apoliporotein A1 and B), fasting plasma glucose, and insulin were determined.
In FH patients, high intensity statin was prescribed only in 17.9% of cases. LDL-Ch levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; p < 0.01), but only 6.9% of FH patients reached the recommended ≥50% LDL-Ch reduction and 16.2% attained the LDL-Ch <2.6 mmol/l target. Simultaneously, 9.6% of FH patients developed new ASCVD, with lower HDL-Ch after 3 years of statin treatment than in those who remained free of ASCVD. In addition, we observed new onset diabetes in 6.4% of FH patients who were more obese, older and with higher fasting glucose at baseline than FH patients free of diabetes, regardless of the type of statin.
These results imply that only a small proportion of FH patients achieved the recommended LDL-Ch treatment targets, mostly due to the use of low statin dose and infrequent implementation of high-intensity statin treatment, which altogether could not prevent the increase in residual cardiovascular risk.
•A small proportion of familial hypercholesterolemia (FH) patients achieved the recommended LDL-Ch treatment targets.•High intensity statin was prescribed in only 17.9% of FH patients.•9.6% of FH patients developed new atherosclerotic cardiovascular disease (ASCVD) during the 3 years of statin treatment.•New onset diabetes was diagnosed in 6.4% of statin treated FH patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UPCLJ, UPUK, ZRSKP
Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this ...follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease.
The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated.
Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same.
Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 2 diabetes is one of the most prevalent chronic diseases in the world today. Insulin resistance - a reduced responsiveness of tissues to insulin - is a hallmark of type 2 diabetes pathology. ...Skeletal muscle plays a pivotal role in glucose homeostasis - it is responsible for the majority of insulin-mediated glucose disposal and thus is one of the tissues most affected by insulin resistance. To study the molecular mechanisms of a disease, researchers often turn to cell models - they are inexpensive, easy to use, and exist in a controlled environment with few unknown variables. Cell models for exploring muscle insulin resistance are constructed using primary cell cultures or immortalised cell lines and treating them with fatty acids, high insulin or high glucose concentrations. The choice of cell culture, concentration and duration of the treatment and the methods for measuring insulin sensitivity, in order to confirm the model, are rarely discussed. Choosing an appropriate and physiologically relevant model for a particular topic of interest is required in order for the results to be reproducible, relevant, comparable and translatable to more complex biological systems. Cell models enable research that would otherwise be inaccessible but, especially when studying human disease, they do not serve a purpose if they are not in line with the biological reality. This review aims to summarise and critically evaluate the most commonly used cell models of muscle insulin resistance: the rationale for choosing these exact treatments and conditions, the protocols for constructing the models and the measurable outcomes used for confirming insulin resistance in the cells.
Aims/hypothesis
Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the ...relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans.
Methods
Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (
n
= 1234) and after a 3 year follow-up (
n
= 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (
M
/
I
) and OGTT (oral glucose insulin sensitivity index OGIS). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance.
Results
Circulating palmitoleate was proportional to fat mass (
r
= 0.21,
p
< 0.0001) and total NEFA levels (
r
= 0.19,
p
< 0.0001). It correlated with whole-body insulin sensitivity (
M
/
I
: standardised regression coefficient std. β = 0.16,
p
< 0.0001), liver insulin resistance (std. β = −0.14,
p
< 0.0001), beta cell function (potentiation: std. β = 0.08,
p
= 0.045) and glucose tolerance (2 h glucose: std. β = −0.24,
p
< 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (
p
= 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07,
p
= 0.04).
Conclusions/interpretation
We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:
We assessed the effect of structured self-monitoring of blood glucose (SMBG), in combination with intensive education, on metabolic control, SMBG frequency, hospitalizations, ...cardiovascular risk factors, and quality-of-life parameters in patients with insulin-treated diabetes in primary health care settings in Serbia.
Methods:
This 6-month, observational, noninterventional study, followed 346 insulin-treated diabetes patients (type 1 diabetes T1D, n = 57; type 2 diabetes T2D, n = 289) from 28 primary care centers. Patients attended a 10-day course at the specialized educational center and were followed monthly by their primary care physicians. Patients used a simple paper tool to document 3-day, 7-point glucose profiles prior to each monthly clinic visit. Physicians reviewed the completed forms at each visit and used a standardized education program to provide remedial training. Changes in HbA1c levels, SMBG frequency, metabolic risk factors, and Diabetes Distress Scale (DDS) were assessed.
Results:
Mean (± SD) HbA1c within the full cohort was significantly improved from baseline at 6 months (8.85 ± 1.17% vs 7.91 ± 1.24%, P < .01). Significant increases in average SMBG frequency per week were seen at 6 months versus baseline (14.6/week vs 4.3/week, P < .001). The mean (± SE) number of hospitalizations due to metabolic conditions was significantly lower during the 6-month study compared to the 6-month period prior to the study (0.14 ± 0.04 vs 0.59 ± 0.09). DDS scores decreased from 39.6 ± 13.9 to 33.9 ± 14.5, P < .01.
Conclusion:
The use of structured SMBG combined with intensive education was associated with clinically significant reductions in HbA1c, increased SMBG frequency, and improved quality of life.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Introduction/Objective. Continuing Medical Education (CME) is a crucial element to keep the level of professionalism in the three key fields of medical education: pre-clinical, clinical, and public ...health. The profile of CME in Serbia has been analyzed for the 2011?2017 period. Methods. Between 2011 and 2017, 11,557 courses of CME have been submitted for accreditation, described by 26 variables. Due to the predominance of nominal data, we employed a principal component analysis (PCA) using the nonlinear iterative partial least squares algorithm (PCA/PLS) to arrange the 16 variables with complete information in such a way that most influential factors could be displayed and ranked. The analysis was done with TIBCO Statistical Software. Results. The Faculty of Medicine of Belgrade takes the top position among the medical faculties in Serbia with 569 courses or 47.9% (n = 1187; 2011?2017), whereas non-educational institutions with 86.2% of all courses (n = 11,514) are the most dominant providers. Clinical topics dominate the thematic spectrum with 59.7%. Between 2012 and 2017, the total number of courses offered diminished by 16.9%. A PCA of 16 potential determinants of CME reveals that the most relevant ones are duration, credit points, price, and number of lecturers. Conclusion. For the last decade, a standstill or even a regression in the development can be observed. Especially the faculties of medicine in Serbia, as well as other major providers, should reconsider the entire structure of their administrative organization and initiate innovative development.
Background/Aim. The hypercoagulable state and inflammation state in diabetics has been widely studied by previous researchers, but there is a lack of research about a possible impact of exercise ...training on this relationship. The aim of this study was to assess and compare correlation between the coagulation and inflammation status in patients with type 2 diabetes mellitus taking into account the gender differences as well as an impact of the 8-week exercise training on the correlation coefficient and parameters of the inflammation and coagulation state. Methods. A total of 60 patients in stable clinical condition and well-regulated diabetic status passed through all phases of the study. The exercise training included the exercise program as interval training with estimated intensity uphill to 75% of a maximal heart rate in particular individual, 5 times a week for 8 weeks, and walking for 30 minutes with a speed of 5 km/h, 5 times a week for 8 weeks. Further fibrinolytic, coagulation and inflammatory parameters were analyzed before and after the study: D-dimer, von Willebrand factor (vWF), fibrinogen, high sensitivity CRP (hs-CRP), leukocytes, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and coagulation factors: FII, FV, FVII and FX. Results. Our research showed a statistically significant reduction in the mean vWF levels after intervention both at the males (p < 0.001) and females (p < 0.001). According to a correlation analysis between hs-CRP and fibrinogen, there was a positive correlation as baseline both at the males (p < 0.05, r = 0.492) and females (p < 0.01, r = 0.516) which became weaker in the males (p < 0.01, r = 0.449) and disappeared in the females (p < 0.05, r = 0.059) after intervention. The correlation which existed as baseline in the males between D-dimer and either hs-CRP (p < 0.01, r = 0.633) or fibrinogen (p < 0.01, r = 0.673) as well as the correlation between hs-CRP and FII (p < 0.01, r = 0.728), FV (p < 0.05, r = 0.366), FVII (p < 0.05, r = 0.373) coagulation as well as between D-dimer and FII (p < 0.01, r = 0.851), FVII (p < 0.05, r = 0.367)was absent in the females. Our research demonstrated a weakening correlations in the males after intervention between D-dimer and hs-CRP (p < 0.05, r = 0.378), between hs-CRP and FII (p < 0.01, r = 0.501), FV (p < 0.05, r = 0.298), FVII (p < 0.05, r = 0.351) as well as between D-dimer and FII (p < 0.01, r = 0.759), and FVII (p < 0.05, r = 0.296). The increase of the FX values (p < 0.05) in the females after intervention suggested the possible antiinflammatory effect of exercise training. Conclusion. According to previous research, the higher levels of vWF was associated with a risk of cardiovascular disease in people with type 2 diabetes mellitus and vWF may be a risk factor unique to these populations. We demonstrated that the 8-week exercise training can significantly reduce the value of vWF in the males and females, suggesting a potential beneficial effect on the endothelial function parameters. Our research demonstrated a stronger correlation between the coagulation and inflammation parameters as baseline in the males than in the females with type 2 diabetes mellitus. According to our results, the 8-week exercise training lead to a weakening of the strength of correlation between the coagulation and inflammation parameters in the males and complete disappearance of this correlation in the females, suggesting a unique effect of exercise training that should be explored in future research.
nema
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: The aim of this study was to investigate the influence of IL-6, TNF-a and hs-CRP on insulin sensitivity during postoperative follow-up in patients with laparoscopic cholecystectomy (LC) ...or open hernia repair (OHR). Methods: 65 patients were studied: after laparoscopic cholecystectomy (LC; n=40) or open hernia repair (OHR; n = 25). Glucose, insulin, hs-CRP IL-6 and TNF-a were determined at day 0 (before the operation) and at days 1, 3 and 7 (after the operation). Results: There were no difference between LC and OHR groups concerning age, BMI, glucose, insulin, hs-CRP IL-6 and TNF-a at day 0. hs-CRP increased at day 1, 3 and 7 vs. day 0 (p<0.0005), without difference between groups (p=0.561). IL-6 increased at day 1 and day 3 vs. day 0 (p<0.005). IL-6 was higher at day 1 in OHR group in comparison with LC group (p=0.044). There were no differences in TNF-a levels between LC and OHR groups (p=0.056). There was increase of HOMA-IR at day 1, 3 and 7 vs. day 0 (p<0.0005) in both groups. Significantly higher increase of HOMA-IR was in OHR group compared with LC group at day 1 (p=0.045). There was a positive correlation between hs-CRP and HOMA-IR (r=0.46; p=0.025) and between IL-6 and HOMA-IR at day 1 in OHR group (r=0.44; p=0.030). Conclusions: Significantly higher HOMA-IR was found in OHR group compared with LC. Positive correlation between hs-CRP and IL-6 with HOMA-IR in OHR group at day 1, indicate possible influen
Continuing Medical Education (CME), conceptualised as lifelong learning (LLL) aims at improving human resources and continuing professional development. Various documents of European institutions ...underline its key importance. This paper therefore tries to analyse the current status of CME and the main deficits in the delivery of LLL courses at medical faculties in Serbia with special consideration of the Faculty of Medicine in Belgrade with detailed financial data available.
Data of 2,265 medical courses submitted in 2011 and 2012 for accredita- tion were made available, thereof 403 courses submitted by 4 medical faculties in Serbia (Belgrade, Kragujevac, Nil, Novi Sad). A subset of more detailed information on 88 delivered courses with 5,600 participants has been provided by the Faculty of Medicine, Belgrade. All data were transferred into an Excel file and analysed with XLSTAT 2009. To reduce the complexity and possible redundancy we performed a principal component analysis (PCA). Correlated component regression (CCR) models were used to identify determinants of course participation.
During the 2-year period 12.9% of all courses were submitted on pre-clinical and 62.4% on clinical topics, 12.2% on public health, while 61.5% of all took place in Belgrade. The subset of the Faculty of Medicine, Belgrade comprised 3,471 participants registered with 51 courses accredited and delivered in 2011 and 2,129 participants with 37 courses accredited and delivered in 2012. The median number of participants per course for the entire period was 45; the median fee rates for participants were 5,000 dinars in 2011 and 8,000 in 2012, resulting together with donations--in a total income for both years together of 16,126,495.00 dinar or almost 144,000.00 euro. This allowed for a median payment of approximately 90 eur per hour lectured in 2011 and 49 euro in 2012. The 2 factors, D1 (performance) and D2 (attractiveness), identified in the PCA for Medical Faculties in Serbia, explain 71.8% of the variance. Most relevant are the duration of the courses, credit points" and hours per credit point gained by lecturers and participants respectively. In the PCA for Belgrade D1 and D2 explain 40.7% of the total variance. The CCR on the number of participants reveals the highest positive impact from the number of lecturers per course and the expenditure on amenities, the highest negative impact from the total income collected per participant.
The faculties of medicine in Serbia should reconsider the entire structure of their organisation of CME, especially to improve the quantity and quality of registration limit the course fee rates per hour and reduce administrative and other costs request lecturing in CME programmes as obligatory for academic promotion and organise a focused marketing.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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