Ekaterina A. Shestakova

Diagnosing Impaired Glucose Tolerance Using Direct Infusion Mass Spectrometry of Blood Plasma

The goal of this study was to evaluate the capacity for mass spectrometry of blood plasma to diagnose impaired glucose tolerance (IGT). For this study, blood plasma samples from control subjects (n = 30) and patients with IGT (n = 20) were treated with methanol and low molecular weight fraction were then analyzed by direct infusion mass spectrometry. A total of 51 metabolite ions strongly associated with IGT were detected. The area under a receiver operating characteristic (ROC) curve (AUC) for diagnosing IGT that was based on an analysis of all these metabolites was 0.93 (accuracy 90%, specificity 90%, and sensitivity 90%). The associated reproducibility was 85%. The metabolites identified were also consistent with risk factors previously associated with the development of diabetes. Thus, direct infusion mass spectrometry of blood plasma metabolites represents a rapid, single-step, and reproducible method for the analysis of metabolites. Moreover, this method has the potential to serve as a prototype for clinical analyses that could replace the currently used glucose tolerance test with a more patient-friendly assay.

Pharmacoeconomic assessment of type 2 diabetes mellitus care on the base of Endocrinology Research Centre, Moscow

Aims. To assess the development of medical care and pharmacological treatment at Endocrine Research Centre (ERC), Moscow, forthe period of 2010-2011 years. Materials and Methods. We analyzed files of 100 patients with type 2 diabetes mellitus (T2DM), who underwent hospitalization to ERCafter January 1, 2010. Key parameters were assessed by means of a study chart, applied for every patient file. Mean values, medians,fractions and confidence intervals (CI) were calculated for studied parameters. Various methods of parametric and non-parametricstatistics were used for comparison of acquired values. Results. Files of 100 patients with T2DM, hospitalized to Endocrinology Research Centre, were analyzed to obtain clinical characteristicsand evaluate initial (prior to hospitalization) and optimized (after hospitalization) therapeutic schemes, as well as spendingpatterns. Mean patient age exceeded 63 years, mean duration period of T2DM was greater than 14.4 years. 86% of patients weredecompensated for glycemic metabolism. 8% were diagnosed with less than 3 diabetes complications, 66% were found to have from 3to 6 complications. Almost all studied cases (98%) featured elevated blood pressure, 63% - diabetic retinopathy on different stages,59% - IHD, 51% - cataract, 49% - CKD. Lower limb angiopathy was found in 30% of cases, diabetic foot syndrome - in 15%.2 patients lost their vision due to diabetic complications and 3 patients experienced lower limb amputation. Arterial hypertension wascompensated in 14 cases from total of 98.Correction of therapy decreased fraction of patients on oral hypoglycemic agents and intermediate acting insulin (NPH), while prescriptionfrequency of short acting insulin and rapid acting human insulin analogues (as well as long acting analogues) showed oppositetrend. Optimization of therapy also included prescription of hypolipidemic drugs for majority of patients, as well as various agents forcorrection of coagulation abnormalities, treatment for CVD and other complications of T2DM.Due to described measures cost of per day treatment for 100 patients increased 2.28 times: from 8 982 RUB to 20 440 RUB (averagecost per day increased from 89.8 RUB to 204.1 RUB).Following the correction, fraction of patients with fasting glycemia 9.0 mmol/l dropped from 37% to 9%, and that with postprandial glycemia >10.0 mmol/l - from 27% to 1%.Mean fasting glycemia level decreased from 8.6 mmol/l to 6.8 mmol/l.Conducted analysis shows that prime expenditures (more that 36% from total cost structure) were associated with hospital stay (includingintensive care unit). Conclusion. Considering expanding nature of DM epidemic, there is an urgent need for effective healthcare management and preventionof severe cardiovascular complications. Priority should be established on balancing efficiency of hypoglycemic agents with theirsafety for short- and long-term prognosis.

Russian multicentre type 2 diabetes screening program in patients with cardiovascular disease

Aim . To evaluate the prevalence of undiagnosed type 2 diabetes mellitus (T2DM) among patients with cardiovascular disease. Materials and methods . T2DM screening programs among patients with cardiovascular disease were held from 2013 to 2014 in several Russian cities. In total, 1001 patients aged ≥40 years with hypertension and/or atherosclerotic disease and without prior diagnosis of T2DM were screened in outpatient cardiology clinics. T2DM diagnosis was based on fasting plasma glucose levels, glycated haemoglobin (HbA1c) and/or oral glucose tolerance test (OGTT) results. Blood pressure (BP), family history of T2DM, cardiovascular disease, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were analysed. Results . Fasting glucose was measured in 1000 (99.8%) patients, HbA1c was measured in in 623 (62.2%) and OGTT was performed in 286 (2.6%). Fasting glucose detected 8% of newly diagnosed T2DM; among patients who underwentHbA1c measurement, the prevalence of T2DM was 10.91%, and among patients who underwent OGTT, the prevalence was 13.99%. Depending on the chosen test, the prevalence of undiagnosed pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) was in the range of 14.4%–36.4%. The majority of patients with T2DM diagnosed by OGTT did not have target blood pressure and lipid levels; 67.5% had elevated systolic BP, 47.5% had elevated diastolic BP, 90.9% had high LDL (≥1.8 mmol/l) and 52.9% had high triglyceride levels (≥1.7 mmol/l). Conclusion . A high prevalence of undiagnosed T2DM (from 8% to 13.99%, depending on the diagnostic criteria) and pre-diabetic state in patients with cardiovascular disease may require screening for T2DM in this high-risk group.

Mass Spectrometry Analysis of Blood Plasma Lipidome as the Method of Disease Diagnostics, Evalution of Effectiveness and Optimization of Drug Therapy

A new method for the analysis of blood lipids based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. Here we demonstrate the versatility and quickness of the method, which significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes mellitus, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.

New glance at pathogenesis of type 2 diabetes mellitus: incretin and antiincretin systems.

Type 2 diabetes mellitus (T2 DM) is often seen in patients with obesity. Bariatric surgery, aimed to decrease body weight, can often help those patientsto improve glycemic status. After some of bariatric operations patients reach normoglycemia in few days, the fact that cant be explained onlyby reduction in weight. Recent trials revealed that the reorganization of gastrointestinal tract provides hypoglycemic effect of such operations. Thisarticle explains the role of proximal and distal gut in pathophysiology of T2 DM.

Second line therapy in type 2 diabetes: legacy effect activation

Type 2 diabetes causes hundred thousand deaths worldwide every year. Though new antidiabetic drugs appear annually and new classes of drugs are invented approximately every ten years still a lot of type 2 diabetic patients remain to be out of the target glycemic levels. According to most of the guidelines for type 2 diabetes,treatment metformin is the first line therapy for this disease. The choice of second-line antidiabetic drug usually depends on doctors’ preference. That is why defining the correct drug for exact patient is still an urgent question. This review provides data on antidiabetic drugspotential for preventing the progression of micro- and macrovascular complications.The question of the potential of early antidiabetic therapy intensification to activate legacy effect is debated. Early and lasting compensation of diabetes with the use of multiple drugs can become a basis for primary prevention of cardiovascular disease in such patients.

Features of carbohydrate metabolism and incretin secretion in patients with Cushing disease and acromegaly

Aim . This study aims to analyse the rhythm and levels of incretins and neuropeptides secretion in patients with Cushing disease (CD) and acromegaly, and thus specify the pathogenesis of carbohydrate metabolism disturbances. Matherials and methods . In this study, 42 patients (mean age, 37.5 years) with CD and acromegaly were enrolled. All patients were newly diagnosed with CD and acromegaly, and none had a history of previous drug therapy, radiotherapy or pituitary surgery. All patients underwent OGTT, during which glucose, glucagon, GLP-1, GLP-2, GIP and ghrelin were evaluated at 0, 30 and 120 min, respectively. Results . During OGTT, glucose levels were not significantly different between the groups. The relevance of pre-diabetes was higher in patients with CD. In these patients, while glucagon levels were substantially higher at all cut-off points than those in controls (р = 0.001), GIP secretion was slightly lower. The acromegaly group was characterised by an inverse rhythm of GIP secretion with no peak level at 30 min. In addition, GLP-1 levels were significantly higher in patients with CD (р = 0.047). Similarly, GLP-2 levels were also significantly higher in patients with CD than in those with acromegaly and controls (p = 0.001). Finally, ghrelin levels were significantly higher in patients with CD (р = 0.013) and acromegaly (р = 0.023). Conclusion . More pleiotropic actions of glucocorticoids can explain the higher relevance of carbohydrate metabolism disturbances in patients with CD. This can also be explained by higher levels of glucagon secretion, which do not depend on the type of carbohydrate metabolism disorder and are stimulated by a direct action of glucocorticoids on the glucagon receptor. GIP and GLP-1 secretion in patients with CD and acromegaly are characterised by the inverse rhythm with no peak levels, implying that these hormones do not play a crucial role in the development of carbohydrate disturbances in these patients. In contrast, GLP-2 and ghrelin seem to influence and potentially regulate glucose homeostasis in patients with CD and acromegaly.