Drawing lines in the sand: The growing threat of obesity in type 1 diabetes.

In this editorial, we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024. We focus on the epidemiological, pathophysiological, and clinical interplay between obesity and type 1 diabetes mellitus (T1DM). Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule. Chronic exogenous insulin administration, genetic and epigenetic factors, and psy-chosocial and behavioral parameters, along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity, set the stage for the increasing obesity rates in T1DM. As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands, it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes. Stereotypes regarding strict dividing lines between "autoimmune" and "metabolic" phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches, instead of individualized diabetes care. In this context, the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

The Current Place of DPP4 Inhibitors in the Evolving Landscape of Type 2 Diabetes Management: Is It Time to Bid Adieu?

During the last decade, the landscape of type 2 diabetes (T2D) management has been completely transformed, moving from a glucose-centric perspective to a holistic approach that also takes into account weight control and organ protection. Dipeptidyl peptidase-4 inhibitors (DPP4i) are oral agents that have been used for the treatment of T2D for almost 20 years. Although they present an excellent safety profile, including the risk of hypoglycemia, they lack the spectacular cardiorenal benefits and weight-loss effects of the newer antidiabetic agents. This poses the question of whether they still deserve a place in the arsenal of drugs against T2D. In this article, we use a hypothetical case scenario to illustrate possible patient profiles where DPP4i could prove useful in the clinical setting. We discuss the advantages and disadvantages of the category, focusing on glycemic control, weight management, and cardiorenal protection, which are the pillars of modern T2D management, also considering its safety profile and cost-effectiveness. We conclude that in most cases, DPP4i present a more favorable risk-benefit ratio compared to sulfonylureas, which are still widely prescribed throughout the world. We also suggest that future research should clarify the reasons behind the contradictory findings between human and animal studies on cardiorenal effects of the class and identify subgroups of patients who would derive most benefit with DPP4i treatment.

The Impact of Metabolic Syndrome Components on Erectile Function in Patients with Type 2 Diabetes.

Erectile dysfunction is commonly encountered in diabetic patients and in patients with metabolic syndrome; however, only a few studies have assessed patients with metabolic syndrome and type 2 diabetes mellitus (T2DM) regarding their sexual function. The purpose of this study is to examine the effect of metabolic syndrome and its components on the erectile function of T2DM patients. A cross-sectional study including T2DM patients was conducted from November 2018 until November 2020. Participants were evaluated for the presence of metabolic syndrome and their sexual function was assessed using the International Index of Erectile Function (IIEF) questionnaire. A total of 45 consecutive male patients participated in this study. Metabolic syndrome was diagnosed in 84.4% and erectile dysfunction (ED) in 86.7% of them. Metabolic syndrome was not associated with ED or ED severity. Among metabolic syndrome components, only high-density lipoprotein cholesterol (HDL) was associated with ED [x2 (1, n = 45) = 3.894, p = 0.048; OR = 5.5 (95% CI: 0.890-33.99)] and with the IIEF erectile function scores (median 23 vs. 18, U = 75, p = 0.012). Multiple regression analyses showed that HDL was non-significantly associated with the IIEF erectile function scores. In conclusion, among T2DM patients HDL is associated with ED.

The Associations between Kidney Function and Sexual Dysfunction among Males and Females with Type 2 Diabetes Mellitus.

Background and Objectives: Diabetic kidney disease (DKD), expressed either as albuminuria, low estimated glomerular filtration rate (eGFR) or both, and sexual dysfunction (SD), are common complications among type 2 diabetes mellitus (T2DM) patients. This study aims to assess whether an association exists between DKD and SD, erectile dysfunction (ED) or female sexual dysfunction (FSD) in a T2DM population. Materials and Methods: A cross-sectional study was designed and conducted among T2DM patients. The presence of SD was assessed using the International Index of Erectile Function and the Female Sexual Function Index questionnaires for males and females, respectively, and patients were evaluated for DKD. Results: Overall, 80 patients, 50 males and 30 females, agreed to participate. Sexual dysfunction was present in 80% of the study population. Among the participants, 45% had DKD, 38.5% had albuminuria and/or proteinuria and 24.1% had an eGFR below 60 mL/min/1.73 m2. The eGFR was associated with SD, ED and FSD. Moreover, SD and ED were proven as significant determinants for lower eGFR values in multiple linear regression analyses. DKD was associated with lower lubrication scores and eGFR was associated with lower desire, arousal, lubrication and total scores; however, the multivariate linear regression analyses showed no significant associations between them. Older age resulted in significantly lower arousal, lubrication, orgasm and total FSFI scores. Conclusions: SD is commonly encountered in older T2DM patients and DKD affects almost half of them. The eGFR has been significantly associated with SD, ED and FSD, while SD and ED were proven to be significant determinants for the eGFR levels.

Effect of Empagliflozin and Dapagliflozin on Ambulatory Arterial Stiffness in Patients with Type 2 Diabetes Mellitus and Cardiovascular Co-Morbidities: A Prospective, Observational Study.

Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713.

Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

International comparison of glycaemic control in people with type 1 diabetes: an update and extension.

AIMS: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. METHODS: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c (IQR) and proportions of individuals with HbA1c < 58 mmol/mol (<7.5%), 58-74 mmol/mol (7.5-8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15-24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. RESULTS: Median HbA1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c < 58 mmol/mol (<7.5%) were 0.91 (0.90-0.92) for women compared to men, 1.68 (1.65-1.71) for people aged <15 years and 0.81 (0.79-0.82) aged15-24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c  < 58 mmol/l (<7.5%) increased and proportions of people with HbA1c ≥ 75 mmol/mol (≥9.0%) decreased. CONCLUSIONS: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.

Dapagliflozin Does Not Affect Short-Term Blood Pressure Variability in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Increased blood pressure variability (BPV) is associated with increased cardiovascular and all-cause mortality in patients with type-2 diabetes mellitus (T2DM). Sodium-glucose co-transporter 2 (SGLT-2) inhibitors decrease the incidence of cardiovascular events, renal events, and death in this population. This study aimed to evaluate the effect of dapagliflozin on short-term BPV in patients with T2DM. METHODS: This is a secondary analysis of a double-blind, randomized, placebo-controlled trial in 85 patients with T2DM. Subjects were randomized to dapagliflozin 10 mg/day or placebo for 12 weeks. All participants underwent 24-hour ambulatory blood pressure (BP) monitoring with Mobil-O-Graph-NG device at baseline and study-end. SD, weighted SD (wSD), coefficient of variation, average real variability (ARV), and variation independent of mean were calculated for the 24-hour, daytime and nighttime periods. RESULTS: Dapagliflozin reduced 24-hour brachial BP compared with placebo. From baseline to study-end 24-hour brachial BPV indexes did not change with dapagliflozin (SBP-ARV: 11.51 ± 3.45 vs. 11.05 ± 3.35; P = 0.326, SBP-wSD: 13.59 ± 3.60 vs. 13.48 ± 3.33; P = 0.811) or placebo (SBP-ARV: 11.47 ± 3.63 vs. 11.05 ± 3.00; P = 0.388, SBP-wSD: 13.85 ± 4.38 vs. 13.97 ± 3.87; P = 0.308). Similarly, no significant changes in BPV indexes for daytime and nighttime were observed in any group. At study-end, no between-group differences were observed for any BPV index. Deltas (Δ) of all indexes during follow-up were minimal and not different between groups (SBP-wSD: dapagliflozin: -0.11 ± 3.05 vs. placebo: 0.12 ± 4.20; P = 0.227). CONCLUSIONS: This study is the first to evaluate the effects of an SGLT-2 inhibitor on short-term BPV in T2DM, showing no effect of dapagliflozin on all BPV indexes studied. CLINICAL TRIALS REGISTRATION: Trial Number NCT02887677.

Dapagliflozin decreases ambulatory central blood pressure and pulse wave velocity in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVES: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce the incidence of heart failure and death in patients with type-2 diabetes mellitus. Arterial stiffness is a prominent risk factor for heart failure and overall mortality. The aim of this study was to evaluate the effects of dapagliflozin on ambulatory brachial and central blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 diabetes mellitus. METHODS: This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 diabetes mellitus on monotherapy or combination therapy with two of: metformin, sulphonylurea, DPP-4 inhibitor, or insulin. Patients were randomized in a 1 : 1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end. RESULTS: Baseline demographic, clinical and laboratory parameters were similar in the two groups. During follow-up, 24-h brachial SBP/DBP (129.0 ±â€Š12.6/77.3 ±â€Š7.3 vs. 123.2 ±â€Š12.4/75.1 ±â€Š6.4 mmHg; P < 0.001/P = 0.008) and central SBP/DBP (117.4 ±â€Š10.5/78.9 ±â€Š7.3 vs. 113.3 ±â€Š8.8/77.3 ±â€Š6.5 mmHg; P = 0.002/P = 0.047) significantly decreased in dapagliflozin but not in the placebo group. Corresponding reductions of 24-h brachial SBP (-5.8 ±â€Š9.5 vs. -0.1 ±â€Š8.7, P = 0.005) and central SBP (-4.1 ±â€Š8.0 vs. -0.7 ±â€Š7.8; P = 0.046) were greater with dapagliflozin than placebo. Twenty-four-hour heart-rate adjusted augmentation index significantly decreased with dapagliflozin and insignificantly with placebo. Importantly, there was a significant difference in change of estimated 24-h PWV (-0.16 ±â€Š0.32 vs. 0.02 ±â€Š0.27; P = 0.007) favoring dapagliflozin. In generalized linear mixed models including 24-h brachial SBP as a random covariate, the adjusted marginal means of delta 24-h central SBP and delta 24-h PWV were not significantly different between-groups. CONCLUSION: Treatment with dapagliflozin significantly reduces ambulatory brachial and central BP levels and PWV in patients with type-2 diabetes mellitus. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.

The impact of hyperglycemia on urinary albumin excretion in recent onset diabetes mellitus type II.

BACKGROUND: Increased urinary albumin excretion (UAE) in diabetes is a sensitive marker of microvascular injury and a reliable predictor of cardiovascular outcomes. Hypertension-induced hemodynamic pressure load, diabetes-related metabolic processes and large artery stiffening have all been implicated in the development of microalbuminuria. We investigated whether hyperglycemia per se, or rather increased blood pressure (BP) and macrovascular dysfunction, is a stronger predictor of UAE at the earliest stages of diabetes. METHODS: Consecutive newly diagnosed patients with diabetes type 2, who were normoglycemic within a year's time prior to diagnosis, were enrolled. UAE was estimated in 24-h urine samples. Both office and 24-h ambulatory BP was recorded. Arterial stiffness was evaluated by measurement of carotid-femoral pulse wave velocity (PWV) with applanation tonometry. RESULTS: Among 71 newly diagnosed patients with median diabetes duration of just 1 month, 15.5% presented microalbuminuria. UAE did not differ between hypertensive and normotensive diabetics; however, newly diagnosed patients for both hypertension and diabetes exhibited significantly higher levels of UAE, compared to diabetic patients with long-standing hypertension. UAE strongly and significantly correlated with office systolic BP, HbA1c, PWV and estimated glomerular filtration rate. However, in the multivariate analysis adjusting for these factors, only HbA1c was independently associated with UAE (beta = 0.278, p = 0.049). CONCLUSIONS: Hyperglycemic state emerges as a powerful predictor of increased UAE even at the earliest stages of diabetes. The relative contribution of hypertension and macrovascular dysfunction to the development of microalbuminuria seems to be obscured by hyperglycemia, even in patients whose diabetes onset does not exceed a few months' time.

Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors.

Type 2 diabetes mellitus (T2DM) constitutes a global pandemic, representing the 7th cause of death worldwide. Morbidity and mortality of patients with T2DM are gradually increasing, while prevalence of cardiovascular disease (CVD) among these patients is almost 14% greater compared to the general population. Arterial stiffness is nowadays a valuable biomarker of CVD and a promising treatment target in specific patient groups, including those suffering from T2DM. Despite that fact, design of the available studies cannot prove causal relationship. Recently, a new antidiabetic drug class, namely sodium-glucose co-transporter-2 (SGLT-2) inhibitors, has attracted scientific interest, due to their multiple, beneficial, pleiotropic effects, especially those focused on CVD. There is limited relevant literature concerning the effects of SGLT-2 inhibitors on arterial stiffness, while retrieved results might be considered as conflicting. The aim of the present review article is to summarize acquired knowledge regarding the prognostic role of arterial stiffness in T2DM, along with the presentation of retrieved data on the potential role of SGLT-2 inhibitors.

Validation of Neuropad in the Assessment of Peripheral Diabetic Neuropathy in Patients with Diabetes Mellitus Versus the Michigan Neuropathy Screening Instrument, 10g Monofilament Application and Biothesiometer Measurement.

OBJECTIVE: Sudomotor dysfunction is a feature of Diabetic Peripheral Neuropathy (DPN). The indicator plaster Neuropad can provide an easy and accurate way to diagnose DPN. The aim of the present study was to evaluate Neuropad's specificity, sensitivity and accuracy in detecting DPN in patients with Diabetes Mellitus (DM). METHODS: A total of 174 patients with DM (79 with type 1 DM, 88 women), mean age 49.8 ± 16.1 years and mean DM duration 17.3 ± 7.7 years were included in the present study. The following methods were used to diagnose DPN: the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively), application of 10 g monofilament (MONO) and measurement of vibration perception threshold with biothesiometer (BIO). Neuropad was applied to both feet in all patients and according to the presence or absence of color change of the sticker, patients were divided in two groups: group A (n = 82, complete change in color from blue to pink, depicting normal perspiration) and group B (n = 92, incomplete or no change, depicting abnormal perspiration). RESULTS: MNSIQ and MNSIE were positive for DPN in 111 and 119 patients, respectively. BIO was abnormal in 109 and MONO in 59 patients. Sensitivity of Neuropad testing was 95% vs. MONO, 73% vs. BIO, 73% vs. MNSIE and 75% vs. ΜNSIQ. Specificity was 69, 81, 90 and 92%, respectively and accuracy of the test was 78, 76, 78 and 83%, respectively. CONCLUSION: Neuropad has a high sensitivity and specificity in detecting DPN vs. MNSIQ, MNSIE and BIO. Neuropad has a high sensitivity but moderate specificity vs. MONO. The accuracy of the test was high in all measurements.

The Growing Epidemic of Diabetes Mellitus.

BACKGROUND: During the past decades, the prevalence of diabetes (DM) has increased significantly, mainly as a result of continuous rise in the incidence of type 2 DM. According to World Health Organization statistics, >422 million adults globally were suffering from DM in 2014 and a continuous rise in DM prevalence is expected. OBJECTIVE: The present review considers recent epidemiological data providing worldwide estimates regarding the incidence of DM. METHODS: A comprehensive literature search was conducted to identify available data from epidemiological studies evaluating the current burden of DM. RESULTS: Over the past few decades the prevalence of DM has risen significantly in nearly all countries and may be considered as a growing epidemic. Urbanization and income status are major factors which influence current rates in the prevalence studies introducing interesting differences between several population groups. CONCLUSION: Having recognized the global burden of DM, we now realize the urgent need for effective interventions. In order to monitor the public-health strategies and design effective future interventions we need reliable global estimates regarding the prevalence of DM.

Glycemic efficacy and safety of glucagon-like peptide-1 receptor agonist on top of sodium-glucose co-transporter-2 inhibitor treatment compared to sodium-glucose co-transporter-2 inhibitor alone: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment. RESEARCH DESIGN AND METHODS: PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates. RESULTS: We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I2 = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I2 = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I2 = 0%) [GRADE: low] were documented. No other safety issues were identified. CONCLUSIONS: This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.

Effect of Nebivolol and Olmesartan on 24-Hour Brachial and Aortic Blood Pressure in the Acute Stage of Ischemic Stroke.

BACKGROUND: Elevated blood pressure (BP) in the acute phase of ischemic stroke is associated with heightened risk of early disability and death. However, whether BP-lowering in this setting is beneficial and the exact levels at which BP should be targeted remain unclear. This study aimed to evaluate the effect of nebivolol, olmesartan, and no-treatment on 24-hour BP in patients with hypertension during the acute poststroke period. METHODS: In a single-blind fashion, 60 patients with acute ischemic stroke and clinic systolic BP (SBP) 160-220 mmHg were randomized to nebivolol (5 mg/day), olmesartan (20 mg/day), or no-treatment between Day 4 and Day 7 of stroke onset. BP-lowering efficacy was assessed through 24-hour BP monitoring using the Mobil-O-Graph device (IEM, Germany). RESULTS: Between baseline and Day 7, significant reductions in 24-hour brachial SBP were noted with nebivolol and olmesartan, but not with no-treatment. Change from baseline (CFB) in 24-hour brachial SBP was not different between nebivolol and olmesartan groups (between-group difference: -3.4 mmHg; 95% confidence interval (CI): -11.2, 4.3), whereas nebivolol was superior to no-treatment in lowering 24-hour brachial SBP (between-group difference: -7.8 mmHg; 95% CI: -7.8 mmHg; 95% CI: -15.6, -0.1). Similarly, nebivolol and olmesartan equally lowered 24-hour aortic SBP (between-group difference: -1.9 mmHg; 95% CI: -10.1, 6.2). Nebivolol and olmesartan provoked similar reductions in 24-hour heart rate-adjusted augmentation index and pulse wave velocity. CONCLUSION: This study suggests that during the acute phase of ischemic stroke, nebivolol is equally effective with olmesartan in improving 24-hour aortic pressure and arterial stiffness indices. ClinicalTrials.gov identifier number: NCT03655964.

Increased erythrocyte- and platelet-derived microvesicles in newly diagnosed type 2 diabetes mellitus.

AIM: To investigate the thrombotic microenvironment in early stages of type 2 diabetes mellitus measuring platelet-derived, endothelial-derived and erythrocyte-derived microvesicles. METHODS: We recruited 50 newly diagnosed type 2 diabetes mellitus patients who did not receive glucose-lowering treatment except for metformin and 25 matched non-type 2 diabetes mellitus volunteers. Microvesicles were measured with flow cytometry, glycated haemoglobin with high-performance liquid chromatography and advanced glycation end products with enzyme-linked immunosorbent assay. RESULTS: Type 2 diabetes mellitus patients showed significantly higher levels of platelet-derived microvesicles [195/µL (115-409) vs 110/µL (73-150), p = 0.001] and erythrocyte-derived microvesicles [26/µL (9-100) vs 9/µL (4-25), p = 0.007] compared to non-type 2 diabetes mellitus individuals. Platelet-derived microvesicles were positively associated with fasting blood glucose (p = 0.026) and glycated haemoglobin (p = 0.002). Erythrocyte-derived microvesicles were also positively associated with fasting blood glucose (p = 0.018) but not with glycated haemoglobin (p = 0.193). No significant association was observed between platelet-derived microvesicles (p = 0.126) or erythrocyte-derived microvesicles (p = 0.857) and advanced glycation end products. Erythrocyte-derived microvesicles predicted the presence of type 2 diabetes mellitus, independently of platelet-derived microvesicles. CONCLUSION: In newly diagnosed type 2 diabetes mellitus, ongoing atherothrombosis is evident during the early stages as evidenced by increased microvesicles levels. Furthermore, the association with glycemic profile suggests that microvesicles represent not only a novel mechanism by which hyperglycemia amplifies thrombotic tendency in type 2 diabetes mellitus but also early markers of thrombosis highlighting the need for earlier management of hyperglycemia.

Multimodal Treatment of Homozygous Familial Hypercholesterolemia.

BACKGROUND: Familial Hypercholesterolemia (FH) is an autosomal-dominant genetic disease, associated with premature atherosclerotic Cardiovascular Disease (CVD), especially in its homozygous type (HoFH). OBJECTIVE: The aim of this review is to discuss the safety and efficacy of combination treatments (procedures and drugs) for HoFH. RESULTS: Historically, liver transplantation was used first; however, it is currently considered only as a last resort for some patients. In the mid 70's, LDL aphaeresis was introduced and remains up today the treatment of choice for patients of any age, despite its significant cost. The use of Ezetimibe results in additive 15-20% reductions in LDL-C regardless of the therapeutic approach, while statins are modestly effective in patients with class 4 or 5 mutations, in which LDL Receptors (LDLR) are present. One of the novel drugs for HoFH is Lomitapide, which is a highly effective oral agent, but is also exceedingly expensive ($350, 000/year). Mipomersen is administered every week subcutaneously, is also effective but has been approved only in the US mainly due to injection site reactions up to 80%. Both Lomitapide (mainly) and Mipomersen have been found to promote fat accumulation in the liver, resulting in subsequent serum transaminases elevations. PCSK9 inhibitors are effective in those with partial LDLR presence and function by reducing frequency of LDL apheresis, improve cost effectiveness of treatment. CONCLUSION: Pediatric and adult HoFH treatment needs combination of procedures and drugs. The main treatment is LDL-C apheresis aided by ezetimibe and PCSK9 inhibitors. Lomitapide needs caution, and liver transplantation is an alternative as the last resort.