Development of ALOHa-G Risk Score for Detecting Postpartum Dyslipidemia Among Normoglycemic Women with Previous Gestational Diabetes: Observational Cohort Study.

INTRODUCTION: Previous gestational diabetes (pGD) is associated with a high risk of postpartum dyslipidemia (pD). Our study was aimed at investigating the prevalence of pD and estimating the risk for pD based on metabolic pregnancy parameters in normoglycemic women with pGD. METHODS: 147 women with pGD and normoglycemia after delivery were divided into groups: A (n = 63) with pD and B (n = 84) with normal lipids, defined by the National Cholesterol Education Program's Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report (NCEP ATP III). We recorded age, body mass index (BMI) at conception, fasting glucose (FG), HbA1c, total cholesterol (TC), triglycerides (Tg), low-density lipoprotein (LDL-c), and high-density lipoprotein cholesterol (HDL-c) measured mid-pregnancy and 1-6 months after delivery. GD was diagnosed by 2 h oral glucose tolerance test (OGTT) between the 24th and the 28th week of gestation, which was repeated after delivery to confirm normoglycemia. RESULTS: 42.8% had pD (group A) while 57.2% had normal lipids (group B). Group A was older (36.8 ± 2.7) than B (33.0 ± 4.2 years, p < 0.001) and had a higher BMI (A 31.2 ± 6.4 vs. B 25.5 ± 2.4 kg/m2, p < 0.001). Simultaneously, HbA1c and FG were higher in group A (5.4 ± 0.3, 5.1 ± 0.4) than B (5.2 ± 0.0%, p = 0.001; 4.8 ± 0.0 mmol/L, p < 0.001). Also, group A had higher TC, LDL-c, and Tg [6.6 (6.1-6.9); 4.2 ± 0.4; 2.9 ± 0.8] compared to B [6.2 (5.4-6.9), p < 0.001; 3.4 ± 0.9, p = 0.001; 2.5 ± 0.6, p < 0.001], while the two groups had comparable HDL-c (A: 1.2 ± 0.3 vs. B: 1.2 ± 0.2 mmol/L, p = 0.998). Calculating the cutoff for age, BMI, HbA1c, FG, LDL-c, and Tg (> 35 years, 26.4 kg/m2, 5.2%, 4.8, 3.9 and 2.7 mmol/L, respectively), univariate regression analysis showed a difference for each (p < 0.001). Allocating 1 point to each predictor, we developed ALOHa G score, which showed high accuracy (AUC 0.931, p < 0.001) for risk of pD in normoglycemic women with pGD. According to the ALOHa-G score, more women in group A were at high risk (≥ 4) and medium risk (= 3) (61.9; 34.9) for pD than in group B (4.8; 14.3), with a lower percentage at low risk for PD (≤ 2) in group A than in group B (3.2 vs. 81.0%). CONCLUSION: Our results implied a remarkable occurrence of pD in normoglycemic women with pGD. Also, the ALOHa-G score was developed based on pregnancy metabolic predictors and could be used to identify normoglycemic women with pGD who are at high risk for pD.

Trends of the Prevalence of Pre-gestational Diabetes in 2030 and 2050 in Belgrade Cohort.

The aim of this study was to analyze the trends in diabetes in pregnancy in Belgrade, Serbia for the period of the past decade and forecast the number of women with pre-gestational diabetes for the years 2030 and 2050. The study included the data on all pregnant women with diabetes from the registry of the deliveries in Belgrade, by the City Institute of Public Health of Belgrade, Serbia for the period between 2010 and 2020 and the published data on the deliveries on the territory of Belgrade. During the examined period the total number of live births in Belgrade was 196,987, and the prevalence of diabetes in pregnancy was 3.4%, with the total prevalence of pre-gestational diabetes of 0.7% and overall prevalence of GDM of 2.7%. The average age of women in our study was significantly lower in 2010 compared to 2020. The forecasted prevalence of pre-gestational diabetes among all pregnant women for 2030 is 2% and 4% for 2050 in our cohort. Our study showed that the prevalence of pre-gestational diabetes has increased both among all pregnant women and among women with diabetes in pregnancy in the past decade in Belgrade, Serbia and that it is expected to increase further in the next decades and to further double by 2050.

Maternal and Fetal Outcomes among Pregnant Women with Diabetes.

The aim of this study was to examine the differences in pregnancy complications, delivery characteristics, and neonatal outcomes between women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This study included all pregnant women with diabetes in pregnancy in Belgrade, Serbia, between 2010 and 2020. The total sample consisted of 6737 patients. In total, 1318 (19.6%) patients had T1DM, 138 (2.0%) had T2DM, and 5281 patients (78.4%) had GDM. Multivariate logistic regression with the type of diabetes as an outcome variable showed that patients with T1DM had a lower likelihood of vaginal delivery (OR: 0.73, 95% CI: 0.64-0.83), gestational hypertension (OR: 0.47, 95% CI: 0.36-0.62), higher likelihood of chronic hypertension (OR: 1.88, 95% CI: 1.55-2.29),and a higher likelihood ofgestational age at delivery before 37 weeks (OR: 1.38, 95% CI: 1.18-1.63) compared to women with GDM. Multivariate logistic regression showed that patients with T2DM had a lower likelihood ofgestational hypertension compared to women with GDM (OR: 0.37, 95% CI: 0.15-0.92).Our results indicate that the highest percentage of diabetes in pregnancy is GDM, and the existence of differences in pregnancy complications, childbirth characteristics, and neonatal outcomes are predominantly between women with GDM and women with T1DM.

Impact of comorbidities on the disability progression in multiple sclerosis.

OBJECTIVES: Investigation of the comorbidity burden in persons with multiple sclerosis (PwMS) has become increasingly important. The aim of this study was to investigate the relationships of cardiovascular disease (CVD) comorbidities and type 2 diabetes with the disability progression. MATERIALS & METHODS: The retrospective cohort study was conducted at the Clinic of Neurology, Belgrade. The Belgrade MS population Registry, which comprises 2725 active MS cases, was used as the source of data. The mean duration of the disease was 21.6 ± 12.5 years. Expanded Disability Status Scale (EDSS) was followed in all PwMS in the Registry. In the statistical analysis, the Cox proportional hazard regression analysis and Kaplan-Meier curve were performed. RESULTS: Hypertension statistically significantly contributed to more rapid reaching investigated levels of irreversible disability (EDSS 4.0, 6.0, and 7.0), while the presence of any of the investigated CVD comorbidities and type 2 diabetes significantly contributed to faster reaching EDSS 4.0 and EDSS 6.0. In a multivariable model, progression index (PI) was singled out (HR = 3.171, p < .001), indicating that higher progression index (PI) was an independent predictor of CVD occurrence in MS patients. In the case of type 2 diabetes, PI (p < .001) and MS phenotype (p = .015) were statistically significant in multivariable Cox regression analysis. CONCLUSIONS: Our study confirms the impact of CVD comorbidities and type 2 diabetes in MS on the progression of disability as measured by EDSS in the large cohort of PwMS from the population Registry.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

Prevalence and Metabolic Predictors for Early Diagnosed Prediabetes in Women with Previous Gestational Diabetes: Observational Cohort Study.

INTRODUCTION: Women with previous gestational diabetes (pGD) are at higher risk of prediabetes (PD) after delivery. The aim of this study was to determine the prevalence of and predictors for PD among women with pGD. METHODS: The study included 186 women with pGD treated by lifestyle modification. After delivery, the women were divided into group A (n = 80) with PD and group B (n = 106) with normal glucose tolerance (NGT), defined by the results of the 2-h oral glucose tolerance test at 4-12 weeks after delivery. We recorded age, body mass index (BMI) at conception and after delivery, fasting glucose (FG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and the Tg/HDL-c ratio measured in the third trimester of pregnancy. RESULTS: Of the 186 women with pGD enrolled in the study, 43% showed prediabetes at 4-12 weeks after delivery, with 13.9% of these women showing impaired FG (IFG), 12.9% showing impaired glucose tolerance (IGT) and 16.2% with IFG/IGT. The groups differed in terms of age and BMI at conception and after delivery. In the third trimester of pregnancy, HbA1c was higher in women in group A than in those in group B (mean ± standard deviation: 5.6 ± 0.4 vs. 5.2 ± 0.3%; p < 0.001), while FG was comparable. Compared to women in group B, women in group A had higher TC (7.1 ± 0.8 vs. 6.6 ± 1.0 mmol/L), Tg (2.7 ± 0.9 vs. 2.1 ± 0.6 mmol/L) and LDL-c (4.7 ± 0.8 vs. 4.3 ± 1.0 mmol/L) (all p < 0.001), lower HDL-c (1.0 ± 0.2 vs. 1.4 ± 1.0; p < 0.001) and higher median Tg/HDL-c (5.4 [range 4.6-14.3] vs. 4.9 [range 1.1-11.5]; p < 0.001). Univariate analysis found an association between prediabetes and age, BMI at conception and after delivery, HbA1c, TC, LDL-c, HDL-c, Tg and Tg/HDL-c ratio. Of these variables, the multivariate analysis showed age (odds ratio [OR] 1.19; p < 0.001), HbA1c (OR 31.06; p < 0.001), Tg (OR 4.09; p < 0.001) and LDL-c (OR 2.00; p = 0.005) as predictors for prediabetes. CONCLUSION: High prevalence of early diagnosed PD in women with pGD was accompanied by advanced age and higher BMI at conception and after delivery. Moreover, age, HbA1c, Tg and LDL-c were predictors for PD.

Targeting Mitochondria in Diabetes.

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

Redesigning diabetes care delivery in Serbia, using JA CHRODIS Recommendations and criteria.

INTRODUCTION: Managing non-communicable diseases (NCDs) requires redesigning health care delivery to achieve better coordination of services at all levels of health care. The aim of this study was improving prevention and strengthening high quality of care for NCDs by using type 2 diabetes as a model disease. METHODS: The mix method approach served to analyse the impact of the intervention processes. Source of information were routine health statistics, interviews and observation. Key Performance Indicators in defined Improvement Areas assisted in the quality of diabetes care assessment. RESULTS AND DISCUSSION: During the study the National Diabetes Centre (NDC) was established. The NDC experts organized numerous educational events, 316 physicians and nurses have participated. New electronic data base was implemented in 20 pilot Primary Health Care Centres (PHCCs) with 38,833 electronic diabetes records. CONCLUSIONS: The intervention led to establishment of the NDC, strengthening competences of health care professionals and to the renewal of the Diabetes Care Units in PHCCs included in the study.

Could the performance of oral glucose tolerance test contribute to the brain health-focused care in multiple sclerosis?

BACKGROUND: It has not been clarified yet if persons with multiple sclerosis (MS) are at increased risk to develop glucose metabolism dysregulation. The aims of the present study were to evaluate glucose metabolism characteristics in persons with MS and to compare it to the healthy individuals; to examine the association of glucose metabolism with the level of disability and its progression. METHODS: The study enrolled 78 patients with MS and 26, comparable for age, gender and body mass index (BMI), healthy controls (HC). Disability and its progression were evaluated by the Expanded Disability Status Scale (EDSS) score, progression index (PI) and multiple sclerosis severity score (MSSS). All participants performed an oral glucose tolerance test (OGTT). Insulin and lipid parameters were analyzed. RESULTS: Fasting glucose concentrations (5.3±0.7 in MS patients vs. 4.5±0.9 mmol/L in HC, p=0.001) and 2 hour post-load glucose concentrations were statistically significantly higher in MS patients compared with controls. Glucose levels at all different time points during OGTT, baseline insulin, Homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol and LDL were statistically significantly (p<0.05) associated with MS, in univariable logistic regression analysis. Glucose level at 120' was independently associated with MS (OR=3.937, 95% CI 1.178-13.159, p=0.026), in the multivariable model. The prevalence of IR was 64.1% in the MS group compared to 30.8% in the control group (p=0.008), based on HOMA-IR. EDSS and Multiple sclerosis severity score (MSSS) were associated with glucose levels at different time points (p<0.05). According to the ROC analysis, best cut-off value for HOMA-IR is 2.3, providing both sensitivity and specificity of 66.7% in discriminating persons with MS and HC. CONCLUSION: Our results demonstrate the presence of higher prevalence of IR in MS patients compared to healthy individuals, and strong association between impaired glucose metabolism and disability. Finally, it has to be emphasized that further studies are warranted to confirm our findings implicating that MS patients have significantly higher risk of impaired glucose metabolism, which could suggest the potential importance of the performance of OGTT in patients with this disorder.

Evaluation of Glycaemic Control, Glucose Variability and Hypoglycaemia on Long-Term Continuous Subcutaneous Infusion vs. Multiple Daily Injections: Observational Study in Pregnancies With Pre-Existing Type 1 Diabetes.

INTRODUCTION: We evaluated the effectiveness of long-term continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin (MDI) injections for glycaemic control and variability, hypoglycaemic episodes and maternal/neonatal outcomes in pregnant women with pre-existing type 1 diabetes (pT1D). METHODS: Our observational cohort study included 128 consecutive pregnant women with pT1D, who were treated from 1 January 2010 to 31 December 2017. Of 128 participants, 48 were on CSII and 80 were on MDI. Glycaemic control was determined by glycated haemoglobin (HbA1c) (captured in preconception and each trimester of pregnancy). Glucose variability (GV) was expressed as the coefficient of variation (CV) [calculated from self-monitoring of blood glucose (SMBG) values], and hypoglycaemia was defined as glucose values < 3.9 mmol/l. The data on maternal and neonatal outcomes were collected from obstetrical records. RESULTS: Duration of the treatment was 8.8 ± 5.3 years in the CSII and 12.6 ± 8.0 years in the MDI group. The CSII lowered HbA1c in preconception (7.1 ± 0.1 vs. 7.9 ± 0.2%, p = 0.03) and the first (6.9 ± 0.1 vs. 7.7 ± 0.2%, p = 0.02), second (6.6 ± 0.1 vs. 7.2 ± 0.1%, p = 0.003) and third (6.5 ± 0.1 vs. 6.8 ± 0.1%, p = 0.02) trimesters significantly better than MDI. Significantly lower CV was observed only for fasting glycaemia in the first trimester (17.1 vs 28.4%, p < 0.001) in favour of CSII. Moreover, the CSII group had significantly lower mean hypoglycaemic episodes/week/patient only during the first trimester (2.0 ± 1.7 vs 4.8 ± 1.5, p < 0.01). In early pregnancy, the majority of women on CSII had less hypoglycaemia than on MDI (0-3: 79.1 vs. 29.1%; 4-6: 18.8 vs. 65.8%; ≥ 7: 2.1 vs. 5.1%, p < 0.01, respectively). We found no difference in the incidence of adverse maternal/neonatal outcomes. CONCLUSIONS: Treatment with CSII resulted in a favourable reduction of HbA1c in the preconception period and each trimester in pregnancy. Moreover, long-term CSII treatment demonstrated more stable metabolic control with less GV of fasting glycaemia and fewer hypoglyacemic episodes only during early pregnancy.

Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis.

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. ß] = 0.16, p < 0.0001), liver insulin resistance (std. ß = -0.14, p < 0.0001), beta cell function (potentiation: std. ß = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. ß = -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. ß = 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.

Evidence from routine clinical practice: EMPRISE provides a new perspective on CVOTs.

EMPA-REG OUTCOME is recognised by international guidelines as a landmark study that showed a significant cardioprotective benefit with empagliflozin in patients with type 2 diabetes (T2D) and cardiovascular disease. To assess the impact of empagliflozin in routine clinical practice, the ongoing EMPRISE study is collecting real-world evidence to compare effectiveness, safety and health economic outcomes between empagliflozin and DPP-4 inhibitors. A planned interim analysis of EMPRISE was recently published, confirming a substantial reduction in hospitalisation for heart failure with empagliflozin across a diverse patient population. In this commentary article, we discuss the new data in the context of current evidence and clinical guidelines, as clinicians experienced in managing cardiovascular risk in patients with T2D. We also look forward to what future insights EMPRISE may offer, as evidence is accumulated over the next years to complement the important findings of EMPA-REG OUTCOME.

SGLT2 inhibitors in T2D and associated comorbidities - differentiating within the class.

BACKGROUND: For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. EXPERT OPINION: To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. CONCLUSION: CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

The Impact of the International Cooperation On Familial Hypercholesterolemia Screening and Treatment: Results from the ScreenPro FH Project.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is often perceived and described as underdiagnosed and undertreated, though effective treatment of FH is available. Owing to the mentioned facts, it is ever more imperative to screen and treat FH patients. Subsequent to the identification of patients, the project focuses on the improvement of their prognoses. The ScreenPro FH project was established as a functional international network for the diagnosis, screening, and treatment of FH. Individual countries were assigned goals, e.g., to define the actual situation and available treatment. With "central support," more centers and countries participated in the project. Subsequently, individual countries reported the results at the beginning and end of the project. Collected data were statistically evaluated. RECENT FINDINGS: The increasing number of patients in databases, from 7500 in 2014 to 25,347 in 2018, demonstrates the improvement in overall effectiveness, as well as an increase in the number of centers from 70 to 252. Before all, LDL-C decreased by 41.5% and total cholesterol by 32.3%. As data from all countries and patients were not available at the time of the analysis, only those results from 10 countries and 5585 patients at the beginning of the project and at the time of writing are included. Our data are quite positive. However, our results have only limited validity. Our patients are far from the target levels of LDL-C. The situation can be improved with the introduction of new therapy, PCSK9-i, evolocumab, and alirocumab. International cooperation improved the screening of FH and finally led to an improvement in cardiovascular risk.

Impact of acute hyperglycemia on layer-specific left ventricular strain in asymptomatic diabetic patients: an analysis based on two-dimensional speckle tracking echocardiography.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Inflammatory and Hemostatic Cardiovascular Risk Markers During Acute Hyperglycemic Crisis in Type 1 and Type 2 Diabetes.

BACKGROUND: We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). METHODS: In that context, we included group A: N = 20 obese, B: N=20 lean patients with DKA; C: N = l0 obese, D: N=10 lean patients with HHS; E: N = 15 obese, F: N=15 lean controls. CRP IL-6, homocysteine were determined by ELISA. RESULTS: Our results showed that CRP IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 µmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homocysteine levels turned out to be similar to controls. CONCLUSIONS: AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP.

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC).

BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

The effects of 3-year statin therapy and the achievement of LDL cholesterol target values in familial hypercholesterolemia patients: An experience from Serbia.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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 ±â€¯1.19 mmol/l) vs. baseline (4.51 ±â€¯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. CONCLUSIONS: 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 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin.

OBJECTIVE: To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0-10.0% (53-86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA1c from baseline to week 26. RESULTS: In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from -1.1% (0.05 mg) to -1.9% (0.3 mg) and with liraglutide from -0.5% (0.3 mg) to -1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was -0.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8-54.0% and 21.9-41.5% of patients, respectively. CONCLUSIONS: Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.

mTOR Inhibitor Therapy and Metabolic Consequences: Where Do We Stand?

mTOR (mechanistic target of rapamycin) protein kinase acts as a central integrator of nutrient signaling pathways. Besides the immunosuppressive role after solid organ transplantations or in the treatment of some cancers, another promising role of mTOR inhibitor as an antiaging therapeutic has emerged in the recent years. Acute or intermittent rapamycin treatment has some resemblance to calorie restriction in metabolic effects such as an increased insulin sensitivity. However, the chronic inhibition of mTOR by macrolide rapamycin or other rapalogs has been associated with glucose intolerance and insulin resistance and may even provoke type II diabetes. These metabolic adverse effects limit the use of mTOR inhibitors. Metformin is a widely used drug for the treatment of type 2 diabetes which activates AMP-activated protein kinase (AMPK), acting as calorie restriction mimetic. In addition to the glucose-lowering effect resulting from the decreased hepatic glucose production and increased glucose utilization, metformin induces fatty acid oxidations. Here, we review the recent advances in our understanding of the metabolic consequences regarding glucose metabolism induced by mTOR inhibitors and compare them to the metabolic profile provoked by metformin use. We further suggest metformin use concurrent with rapalogs in order to pharmacologically address the impaired glucose metabolism and prevent the development of new-onset diabetes mellitus after solid organ transplantations induced by the chronic rapalog treatment.