76 research outputs found
Identifying the unmet needs of individuals with Type 2 diabetes: an international web-based survey
Aim: To identify and understand the main unmet needs of individuals with Type 2 diabetes (T2D). Materials & methods: An online survey was conducted in Brazil, China and Russia of individuals with recently diagnosed T2D. Results: The survey, involving 300 individuals with T2D, identified a need for more information regarding food/diet and for increased awareness of T2D symptoms. While most participants (94%) had experienced symptoms prior to their diagnosis, only 55% of symptomatic individuals sought medical attention. Conclusion: Novel strategies to increase awareness of diabetes should be developed and tested, and may enable earlier diagnosis and improve patients' quality of life.publishersversionpublishe
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Targeting of reactive isolevuglandins in mitochondrial dysfunction and inflammation.
Inflammation is a major cause of morbidity and mortality in Western societies. Despite use of multiple drugs, both chronic and acute inflammation still represent major health burdens. Inflammation produces highly reactive dicarbonyl lipid peroxidation products such as isolevuglandins which covalently modify and cross-link proteins via lysine residues. Mitochondrial dysfunction has been associated with inflammation; however, its molecular mechanisms and pathophysiological role are still obscure. We hypothesized that inflammation-induced isolevuglandins contribute to mitochondrial dysfunction and mortality. To test this hypothesis, we have (a) investigated the mitochondrial dysfunction in response to synthetic 15-E2-isolevuglandin (IsoLG) and its adducts; (b) developed a new mitochondria-targeted scavenger of isolevuglandins by conjugating 2-hydroxybenzylamine to the lipophilic cation triphenylphosphonium, (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium (mito2HOBA); (c) tested if mito2HOBA protects from mitochondrial dysfunction and mortality using a lipopolysaccharide model of inflammation. Acute exposure to either IsoLG or IsoLG adducts with lysine, ethanolamine or phosphatidylethanolamine inhibits mitochondrial respiration and attenuates Complex I activity. Complex II function was much more resistant to IsoLG. We confirmed that mito2HOBA markedly accumulates in isolated mitochondria and it is highly reactive with IsoLGs. To test the role of mitochondrial IsoLGs, we studied the therapeutic potential of mito2HOBA in lipopolysaccharide mouse model of sepsis. Mito2HOBA supplementation in drinking water (0.1 g/L) to lipopolysaccharide treated mice increased survival by 3-fold, improved complex I-mediated respiration, and histopathological analyses supported mito2HOBA-mediated protection of renal cortex from cell injury. These data support the role of mitochondrial IsoLG in mitochondrial dysfunction and inflammation. We conclude that reducing mitochondrial IsoLGs may be a promising therapeutic target in inflammation and conditions associated with mitochondrial oxidative stress and dysfunction
How close can one approach the Dirac point in graphene experimentally?
The above question is frequently asked by theorists who are interested in
graphene as a model system, especially in context of relativistic quantum
physics. We offer an experimental answer by describing electron transport in
suspended devices with carrier mobilities of several 10^6 cm^2V^-1s^-1 and with
the onset of Landau quantization occurring in fields below 5 mT. The observed
charge inhomogeneity is as low as \approx10^8 cm^-2, allowing a neutral state
with a few charge carriers per entire micron-scale device. Above liquid helium
temperatures, the electronic properties of such devices are intrinsic, being
governed by thermal excitations only. This yields that the Dirac point can be
approached within 1 meV, a limit currently set by the remaining charge
inhomogeneity. No sign of an insulating state is observed down to 1 K, which
establishes the upper limit on a possible bandgap
Psychosocial aspects of the usage of modern technologies in diabetes mellitus
This article represents a review of trials on the relationship between the use of modern technologies in the treatment of diabetes, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and the psychological characteristics of patients. The review includes Russian studies and foreign publications. The analysis showed that the psychological aspects of using CSII are considered more often than CGM. Most Russian authors agree that the use of technology is associated with an increased psychological well-being of patients. Foreign researchers generally agree with the same point of view but also report a weaker correlation. One of the most significant conclusions of this analysis is that the use of modern technologies itself does not guarantee an improved quality of life (QOL) and psychological well-being, but technologies such as CSII and CGM provide patients with opportunities to achieve greater effectiveness in treating diabetes, improving clinical and metabolic parameters and therefore improving QOL. However, the use of these devices, as well as many other technological tools, is associated with certain psychological problems, both in terms of their acquisition and influence on patients’ subjective well-being. Early diagnosis and prevention of such problems should be one of the tasks in preparing patients for the use of modern technologies. A positive effect on both clinical and metabolic indicators as well as on the mental sphere and social life of patients can be achieved only by combining complete training (optimally—according to specialised programmes) with medical support
A look at new therapeutic opportunities in patients with non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is considered to be the liver manifestation of metabolic syndrome. Currently, there is no etiotropic treatment of NAFLD, so an active research for new methods of treatment is underway. In the meantime, drugs are used to treat comorbid conditions, such as dyslipidemia, arterial hypertension, obesity, type 2 diabetes, which are present in varying degrees in patients. This review considers medications that are used in patients with NAFLD and related concomitant features, and also describes new strategies for regressing changes in liver tissue in NAFLD. In our opinion, one of the promising groups of drugs are agonists of the farnesoid X receptor (FXR). FXR belongs to the group of nuclear receptors, which are ligand-activated transcription factors that regulate the genes involved in metabolism. FXR agonists can claim to be a new promising drug for the treatment of NAFLD and related diseases influencing carbohydrate metabolism, fat metabolism, bile acid metabolism, as well as inflammatory processes in the liver to ensure metabolic homeostasis
Atomically thin boron nitride: a tunnelling barrier for graphene devices
We investigate the electronic properties of heterostructures based on
ultrathin hexagonal boron nitride (h-BN) crystalline layers sandwiched between
two layers of graphene as well as other conducting materials (graphite, gold).
The tunnel conductance depends exponentially on the number of h-BN atomic
layers, down to a monolayer thickness. Exponential behaviour of I-V
characteristics for graphene/BN/graphene and graphite/BN/graphite devices is
determined mainly by the changes in the density of states with bias voltage in
the electrodes. Conductive atomic force microscopy scans across h-BN terraces
of different thickness reveal a high level of uniformity in the tunnel current.
Our results demonstrate that atomically thin h-BN acts as a defect-free
dielectric with a high breakdown field; it offers great potential for
applications in tunnel devices and in field-effect transistors with a high
carrier density in the conducting channel.Comment: 7 pages, 5 figure
Assessment the equivalence of the bioanalogue insulin lizpro biphasic 25 (Geropharm-bio, Russia) and Humalog® Mix 25 (Lilly France, France) using the euglycemic hyperinsulinum clamp method on healthy volonters
Background: Modern medicine requires use of effective antidiabetic drugs that can imitate the natural profile of insulin in the body of patients with diabetes mellitus. Examples of such preparations include biphasic insulin lispro, which is a mixture of insulin lispro ultra-short action and insulin lispro protamine suspension with prolonged effect. The clinical trials (CT) program for biosimilar insulins contains pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety studies. Aims: To demonstrate Biphasic Insulin Lispro 25, suspension for subcutaneous administration, 100 U/ml (GEROPHARM-Bio, Russia) and Humalog® Mix 25, suspension for subcutaneous administration, 100 U/ml (Lilly France, France) have comparable pharmacokinetic profiles under conditions of hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers. Materials and methods: The study was conducted on 48 healthy men aged between 18 to 50 years. This was a double-blind, randomized, crossover study of comparative pharmacokinetics of drugs. The investigational products (IP) were administered before the clamp in a single dose of 0.4 U/kg subcutaneously in the abdominal wall. Regular blood sampling was performed during the study. The insulin concentrations in the samples were determined using an ELISA method. The results of the determination were used to calculate the PK parameters and construct the concentration-time curves. Adjust glucose infusion rates were based on blood glucose measurements. These data were used to calculate the PD parameters. Results: Our results demonstrated that Biphasic Insulin Lispro 25 and Humalog® Mix 25 have comparable PK and PD profiles under conditions of HEC in healthy volunteers. The confidence intervals for the ratio of the geometric mean for Cins.max and AUCins.0–12 were 87.75–99.90% and 83.76–96.98% respectively, which were well within 80–125% limits for establishing comparability. Conclusions: Biphasic Insulin Lispro 25 and Humalog® Mix 25 are equivalent based on this CT applying the HEC technique in healthy volunteers
MODY2 diagnostic issues in adults
Approximately 90% of all cases of diabetes mellitus in adults involve type 2 diabetes, while the prevalence of maturity-onset diabetes of the young (MODY) remains undetermined leading to inappropriate treatment regimens. One of the most common monogenic forms of diabetes is a disease caused by a mutation in the glucokinase gene, MODY2. Knowledge of the clinical features of the disease allows the selection of patients with a high risk of mutation in the glucokinase gene and verification of diagnosis for molecular genetic research. This paper reflects the clinical features of MODY2 and the difficulties of diagnosis in adults. Furthermore, it presents a clinical case of a patient with MODY2 demonstrating all the features of this type of diabetes. A family member with a mutation in the gene allows to predict the nature of carbohydrate metabolism disorders in first degree relatives. A targeted study of only one part of the glucokinase gene in molecular genetic research is sufficient to confirm the diagnosis in relatives
Epidemiology of acute diabetes complications (coma) according to the Federal Diabetes register of the Russian Federation (2013–2016)
Background: Despite the improvement in the quality of diabetes care in the Russian Federation (RF), coma remain one of the causes of death in patients with diabetes. Aim: To assess dynamic of epidemiological characteristic of acute complications in adult patients with T1D and T2D in 2013–16. Materials and methods: The database of the Russian Federal Diabetes register (81 regions). The indicators of coma for 2013–16 were estimated for 10000 adult patients with diabetes (>18 years). Results: In 2016, the prevalence of coma in RF was 225.9 with T1D and 11.6/10000 adults with T2D. For the period from 2007 the prevalence of ketoacidotic coma decrease three times in T1D, 4 times for T2D.Totally in 2016, 165 new cases of coma for both types of diabetes were registered, an average of 0.4/10000 adults. Interregional differences in the prevalence of coma were observed 0–4.2/10000 adults. The frequency of new cases of coma has a tendency to decrease: 0,9→0,4/10000 adults: T1D 5.7→3.4, T2D 0.6→0.2/10000 adults. When evaluating the structure of coma, redistribution is evident in their form. So in 2016 the proportion of hypoglycemic coma increased to 40.7%, and ketoacidotic coma decreased to 56.6% in T1D. With T2D, the difference expressed in a lesser degree. The mean duration of diabetes at the time of coma development increased with T1D from 3.8→9.1 years, with T2D 3.5→7.0 years. The maximum frequency of development of coma is recorded with the diabetes duration more than 30 years, regardless of the type. The patients’ age at the time of coma development in T1D increased to 27.5 years old, and in T2D it was 60.4 years, it didn’t change significantly. The assessment of glycemic control showed a significant improvement: a decrease in the proportion of patients with HbA1c≥ 9.0% (23% with T1D, 8.8% with T2D), an increase with HbA1c <7% (32.4% and 51.7%, respectively). The average value of HbA1c in 2016 with T1D – 8.21%, with T2D – 7.48%. Conclusions: It is established that the dynamics of the frequency of development of coma in 2013–16 in adult patients with diabetes in the RF has a stable tendency to decrease: 1.5 times with T1D and more than 3 times with T2D. It can be assumed that this is due to the improvement in the quality of diabetes care and glycemic control in general, as well as the use of modern medicines. Attention is required to draw to the high frequency of coma in T1D, the development of coma with a longer duration of diabetes, an increase in the proportion of patients with hypoglycemic coma. Significant interregional differences in the frequency of coma registration require additional analysis
Evaluation of biosimilarity of RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) using the euglycemic hyperinsulinemic clamp technique in patients with type 1 diabetes: double-blind randomized clinical trial
Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research.Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016.Materials and methods: The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters.Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUCins0-T, and 85.43% - 115.64% for the PD-parameter AUCGIR0_T, which fall within the specified limits of 80% - 125% to establish comparability between drugs.Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®
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