The effect of OMEGA-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in patients with type 2 diabetes mellitus and cardiovascular autonomic neuropathy

Background: Cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus (T2DM), which is characterized by lesion of nerve fibers in parasympathetic and sympathetic nervous system is one of the leading causes of heart arrhythmias and an independent risk factor for cardiovascular mortality in patients with T2DM. Therefore, the problem of effective treatment of CAN is particularly relevant. Aims: To analyze the effect of long-chain polyunsaturated fatty acids (ω-3 PUFAs) on ambulatory blood pressure monitoring parameters in patients with T2DM and CAN. Materials and methods: 36 patients with T2DM and confirmed CAN were divided into two groups. First group received hypoglycemic therapy (n=15, control) for three months; patients in group 2 (n=21) in addition were administered 1 capsule/q.d. of ω-3 PUFAs for three month. Results: Treatment with ω-3 PUFAs led to significant decrease of the diastolic blood pressure (DBP) (p<0,01), diastolic blood pressure load (p<0,05), time index of DBP (p<0,05) during the day; DBP (p<0,05), diastolic blood pressure load (p<0,05), time index of DBP (p<0,05), SD DBP (p<0,01) during the night (compared to the control group). Conclusions: The study showed that prescription of ω-3 PUFAs for three month was effective in decreasing diastolic blood pressure and its parameters among patients with T2DM and CAN

Impact of hypoglycemia on daily life of type 2 diabetes patients in Ukraine

This study evaluates the impact of hypoglycemia on the lives of Ukrainian patients with type 2 diabetes mellitus. The secondary objective was to explore patient-physician relationships and the attitudes of patients towards various informational resources on diabetes management. Three focus groups with 26 patients were conducted. Qualitative information was evaluated using content analysis. The results show that patients with type 2 diabetes mellitus in Ukraine are adapting to potential attacks of hypoglycemia; however, they still experience periodic manifestations of hypoglycemia that significantly affect their psychological well-being. This result is similar to observations made in other countries. Ukrainian patients >40 years old mainly receive information on disease management from endocrinologists, and rarely use internet resources on diabetes management. Information provision was especially important at the early stage of the disease, when patients lack information on hypoglycemia manifestations and could therefore fail to identify and manage it properly

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Serum levels of endothelial monocyte activating polypeptide-II in type 1 diabetes patients with microangyopathy and arterial hypertention.

Aim. Тo determine the serum level of EMAP-II in type 1 diabetic patients with microangyopathy and arterial hypertention. Materials and methods We examined 23 type 1 diabetic patient with microangyopathy and arterial hypertention, 10 type 1 diabetic patient with microangyopathy without hypertention and 28 control subjects. Serum levels of EMAP-II were determined by immunoenzyme assay. The data were presented as means±SD.   Results. We found an increased serum level of EMAP-II in type 1 diabetic patients with microangyopathy and arterial hypertention compared to control group (5,23±1,66 ng/ml and 1,25±0,76 ng/ml respectively, р0,01), and in type 1 diabetic patients with microangyopathy and arterial hypertension compared to group without hypertension (5,23±1,66 ng/ml and 3,63±1,9 ng/ml respectively, р0,01). Also, the level of EMAP-II correlated with key markers of carbohydrate and lipid metabolism, inverse correlated with endothelium-dependent dilatation (p0,05). Conclusion. The revealed change of EMAP-II could reflect an endothelial dysfunction in patients with type 1 diabetes with microangyopathy and arterial hypertension. Arterial hypertension, hyperglycemia, dyslipidemia appears to be significant factor to contributing elevation of EMAP-II. Keywords: Endothelial monocyte activating polypeptide II, endothelial dysfunction, type 1 diabetes, arterial hypertension

CARMELINA: An important piece of the DPP-4 inhibitor CVOT puzzle

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of glucose-lowering agent for type 2 diabetes (T2D) that are commonly used in clinical practice. With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets. To consider how the CARMELINA study may be interpreted, and the relevance for our clinical practice, we convened as an expert group of diabetes specialists from the Central and Eastern Europe region to discuss the new disclosures. Our discussions revealed a general confidence in safety across the class that is further supported by CARMELINA. However, we also concluded that there are important differences in the available evidence level between agents in the setting of heart failure and data on renal outcomes. Here, we noted the clinical relevance to our practice of the study population in CARMELINA, which is unique among CVOTs in including a majority of patients with chronic kidney disease (CKD). Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines

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