Breaking Barriers With Basal Insulin Biosimilars in Type 2 Diabetes.

Despite increases in the availability and effectiveness of other therapies, insulin remains an essential treatment for approximately 30 million people with type 2 diabetes worldwide. The development of biosimilars has created the potential for significant health care cost savings and may lead to greater access to basal insulin for vast populations. In this review, we discuss evidence demonstrating equipoise between basal insulin biosimilars and the patented analogs they may replace.

The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines.

[The role of GLP-1 receptor agonists and their fixed combination with insulin in the treatment of type 2 diabetes mellitus].

Therapy with GLP1 receptors agonists shows various multiorgans benefits. Possible reasons of preference of this treatment are: efficacy, decrease of weight, CV protectivity, slow down the progression of nephropathy, protection of function of B-cells, safety (low risk of hypoglycemia, small incidence of serious adverse events), decrease of blood pressure, lipids, biomarkers of CV risk, markers of chronic subclinical inflammation. In context of individual approach, therapy with GLP1 receptors agonists should be preferably used in early stages of type 2 diabetes mellitus, as second choice treatment after metformin, mainly in more obese patients with subclinical or clinical manifestations of atherosclerosis, but without symptoms of heart failure.

[A consensual therapeutic recommendation for type 2 diabetes mellitus by the Slovak Diabetes Society (2018)].

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before.

KCNQ1 gene polymorphism is associated with glycaemic response to treatment with DPP-4 inhibitors.

Aims: Only afew gene variants were associated with the response to dipeptidylpeptidase-4 inhibitors (DPP4I). KCNQ1 gene variants were previously related both to type 2 diabetes (T2D) and incretin effect. We hypothesized that T2D related KCNQ1 variants would be associated with smaller glucose-lowering effect of DDP4I.

A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins.

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect.

A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.

Purpose: The aim of the present study was to investigate possible associations of the single-nucleotide variants in six genes encoding the key molecules mediating the metformin pharmacodynamic effect with the response to treatment with metformin in patients with type 2 diabetes.

Methods: One hundred forty-eight drug-naïve patients with type 2 diabetes were included in the study. PRKAA1 rs249429, STK11 rs741765, PCK1 rs4810083, PPARGC1A rs10213440, HNF1A rs11086926, and CAPN10 rs3792269 variants were genotyped.

Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.

Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2).

Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes.

Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study.

KCNJ11 gene E23K variant and therapeutic response to sulfonylureas.

Aims: Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K(ATP)) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas.

Variation in CDKAL1 gene is associated with therapeutic response to sulphonylureas.

The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR.

Pharmacogenetics of oral antidiabetic treatment.

In the majority of patients with type 2 diabetes (T2D), oral antidiabetic drug (OAD) treatment is the first line treatment after lifestyle measures fail. Two major groups of OAD are used in clinical practice--insulin secretagogues and insulin sensitisers. Sulphonyluea (SU) derivatives are insulin secretagogues and stimulate insulin secretion by inhibiting ATP-sensitive potassium channels.

Variation in KCNQ1 is associated with therapeutic response to sulphonylureas.

Background: We aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment.

Material/methods: Effect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe.

Relationship between type 2 diabetes mellitus and hypothalamic-pituitary-adrenal axis.

Introduction: Hypercortisolism often leads to impaired glucose tolerance or type 2 diabetes mellitus. On the other hand, changes in the regulation of hypothalamic-pituitary-adrenal axis become a matter of debate in patients with type 2 diabetes mellitus/metabolic syndrome.

Patients, Materials, And Methods: Authors assessed the hypothalamic-pituitary-adrenal axis activity and subclinical Cushing's syndrome occurrence in 50 patients with type 2 diabetes mellitus in comparison to 25 sex-, age-, and BMI-matched control nondiabetic subjects.

Effect of sulphonylurea treatment on glycaemic control is related to TCF7L2 genotype in patients with type 2 diabetes.

The aim of the present study was to analyse effects of sulphonylurea treatment on parameters of glycaemic control in relation to transcription factor 7-like 2 (TCF7L2) genotypes. In 87 patients with type 2 diabetes who failed to achieve glycaemic control on metformin monotherapy, effects of 6-month sulphonylurea in addition to metformin on reductions in haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels were evaluated. Reduction in HbA1c and FPG in response to 6-month sulphonylurea treatment was significantly higher in patients with CC genotype compared to those with the CT+TT genotype (1.

Autoimmune thyroid diseases in patients with diabetes mellitus.

Background And Objectives: Autoimmune thyroid diseases are frequent in patients with type 1 diabetes mellitus. The aim of our study was to determine the incidence of autoimmune thyroid diseases (AIT) in the different groups of patients with DM (DM type 1--classical form, DM type 1--subtype LADA, DM type 2) and compare the incidence of AIT among the groups as well as to the control group of non-diabetics. We also focused our attention on the factors that influence the risk of thyroid diseases incidence in diabetics.

[Affection of cardiovascular system in diabetic patients with thyroid dysfunctions].

Affection of cardiovascular system is one of the most frequent and--especially in higher age groups--the most serious clinical manifestations of thyroid dysfunction. Moreover, diabetics, mainly type 2 diabetes patients, have a marked predisposition to cardiovascular diseases, especially to atherosclerosis and its visceral complications. Simultaneous occurrence of diabetes mellitus (DM) and thyroid dysfunctions involves a very high risk of development and progression of various forms of cardiovascular diseases.

[Autoimmune thyropathies in diabetics].

Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies.

[Factors affecting the vulnerability of the left atrium during rapid transesophageal atrial stimulation].

Atrial fibrillation (AF) is associated with a higher morbidity and mortality because of the risk of systemic or pulmonary embolism as well as the negative impact on cardiac function. The authors investigate in the submitted paper factors influencing the vulnerability of atria during transoesophageal atrial stimulation (TESP). The group comprised 68 patients with a sinus rhythm, mean age 56.

[Non-invasive tests in the diagnosis of sinoatrial node dysfunction].

The authors present a group of 67 patients, mean age 63 +/- 15 years, where they applied on account of suspected dysfunction of the sinoatrial node (SA) the atropine test (AT), 24-hour Holter monitoring and transoesophageal stimulation of the atria (TESP). The objective of the investigation was to test the reliability and yield of the mentioned methods and to investigate more closely the relations of their final indicators. Correlation analysis revealed a positive relationship between the maximal frequency during AT and the mean daily (r = 0.

[The effect of aminophylline on the sinoatrial node].

The objective of the submitted prospective study was to assess the influence of intravenously administered aminophylline on the sinoatrial node. The authors examined by electrophysiological methods 20 patients (16 without dysfunction of the sinoatrial node and 4 with dysfunction of the sinoatrial node). From the investigation patients were eliminated with an apparent and obvious cause of elevated uric acid serum levels and patients where on electrophysiological examination limited values of the corrected recovery time of the sinoatrial node were found (from 650 ms to 999 ms).

[Sick sinus syndrome and permanent cardiac pacing].

The authors submit a retrospective analysis of 140 patients with an affection of the sinoatrial node who had a permanent cardiac pacemaker. The analysis comprises an 18-month period; the patients were from the eastern Slovakian region. The authors emphasize different affections of the sinoatrial node and discuss various ways of permanent cardiac pacing and other types of non-pharmacological treatment (e.

[Uric acid and sinoatrial node function].

In a retrospective investigation comprising 54 patients the authors assessed the relationship between the function of the sinoatrial node and raised serum uric acid levels. The function of the sinoatrial node was expressed by the maximal value of the corrected recovery time of the sinoatrial node. No statistically significant correlation was found.