Obesity and metabolic syndrome are among the major problems of modern society. The increase in obesity is associated with a corresponding increase in type 2 diabetes, cardiovascular disease and cancer. A huge amount of scientific research has been devoted to the development of methods to reduce obesity and its complications. In recent years, attention has shifted towards studying the intestinal microbiota not only as a possible component of the pathological process but also as a target of therapeutic intervention. Recent evidence, primarily from investigations in animal models, suggests that the intestinal microbiota affects nutrient acquisition and energy regulation. This review will discuss the role of the intestinal microbiota in metabolic processes as well as the latest developments on the improvement of disturbances specific to obesity and metabolic syndrome.

A biological function of the phylogenetically late humoral mediator insulin is to provide energy substrates for locomotion, i.e. movement resulting from contraction of striated muscles. Insulin is able to meet this evolutionary demand of an organism by means of the effective ATP production in the mitochondria. Exogenous fatty acids, optimised endogenous fatty acids produced from glucose and glucose itself are the major substrates for ATP synthesis. Cells stimulated by insulin produce ω-9 С18:1 oleic acid from glucose. This fatty acid is oxidised by the mitochondria at a higher rate than exogenous and endogenous C16:0 palmitic fatty acid. In the normal state of insulin system and mitochondria, the frequent cause of insulin resistance is the non-optimal properties of dietary fatty acids supplied for oxidation by the mitochondria. Dietary excess of saturated palmitic fatty acid over monogenic oleic fatty acid causes insulin resistance to develop. Insulin resistance syndrome is the condition of in vivo energy deficiency and insufficient production of ATP for the realisation of the biological adaptation and compensation. Insulin effectively inhibits lipolysis only in phylogenetically late subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. Discrepancy in the regulation of energy substrate metabolism against the background of a ‘relative biological perfection’ of higher mammals is the aetiological basis of insulin resistance.

Aim. To identify the clinical and metabolic factors associated with serum concentration of high sensitivity C-reactive protein (hsCRP) and α1-acid glycoprotein (α1-AGP) in patients with type 2 diabetes.

Material and methods. The study involved 210 patients with type 2 diabetes. Levels of hsCRP and α1-AGP were measured using ELISA and compared with those of the control (30 healthy normal individuals). Levels of acute-phase proteins, fat mass and glucose variability (GV) were compared among demographic, anthropometric, biochemical and haematological parameters. The fat mass was determined with Dual-energy X-ray absorptiometry (DEXA). GV parameters including mean amplitude of glycaemic excursions, continuous overlapping net glycaemic action (CONGA), J-index, M-value and mean absolute glucose change (MAG) were derived from continuous glucose monitoring.

Results. Levels of hsCRP and α1-AGP significantly increased (p < 0.0001) in patients with diabetes compared with controls. hsCRP level positively correlated with total, truncal and android fat (r = 0.34, r = 0.28 and r = 0.31; respectively, p < 0.00004). α1-AGP level showed no relationship with fat mass but positively correlated with mean glucose, CONGA, M-value and MAG (r = 0.38, r = 0.36, r = 0.43 and r = 0.4; respectively, p < 0.0001). Patients with the highest hsCRP levels (>75 percentile) had a greater body mass index (p = 0.00009) as well as truncal and android fat mass (p = 0.04 and p = 0.03, respectively) than those with the lowest levels (<25 percentile). High level of α1-AGP (>75 percentile) was associated with urinary albumin/creatinine ratio (p = 0.01) and GV indices (M-value: p = 0.02, MAG: p = 0.04).

Conclusions. Levels of acute-phase proteins (hsCRP and α1-AGP) increased in patients with type 2 diabetes. Levels of hsCRP were associated with fat mass; meanwhile, α1-AGP levels were associated with short-time GV in these patients. The results lend support to the notion that both obesity and enhanced GV are involved in the development of chronic low-grade inflammation associated with type 2 diabetes.

Type 2 diabetes (T2DM) is one of the key predictors of coronary artery disease (CAD) and its complications. Currently, along with metabolic risk factors for CAD, much attention has been given to the study candidate genes, including platelet fibrinogen receptor gene ITGB3 and the gene NOS3 of endothelial NO-synthase type 3.

Aim. To estimate the associations of T1565C ITGB3 and T-786C NOS3 polymorphisms with the clinical condition of russian patients from West Siberian region with concomitant development of coronary artery disease and type 2 diabetes.

Materials and methods. The study included 237 CAD patients; 78 (32.9%) of them had T2DM. The genotyping was performed by allele-specific polymerase chain reaction. Comparison of quantitative variables between groups with different genotypes was done by Mann-Whitney U test or Kruskal-Wallis test. Comparison of discrete parameters was done by Pearson χ2 test or Fisher's exact test.

Results. Genotype 786CC (NOS3) (p=0,039) and allele 1565C (ITGB3) (p=0,045) were less common in the group CAD+T2DM than in the group CAD without T2DM. But in the group CAD+T2DM the frequency of obesity was higher among carriers of 1565C allele than in homozygotes 1565TT (p=0,039), and carriers of 786C allele have the highest concentration of glucose compared to homozygous 786TT (p=0,018). Furthermore, 786C allele is associated with obesity in the group of patients without T2DM detected (p = 0,015).

Conclusion. Carriage of 1565C (ITGB3) allele and 786C (NOS3) allele can be considered as predictors of adverse course of the disease at concomitant development of CAD and T2DM.

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, р<0,01), 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, р<0,01). Also, the level of EMAP-II correlated with key markers of carbohydrate and lipid metabolism, inverse correlated with endothelium-dependent dilatation (p<0,05).

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.

Aim. To study the influence of combined therapy on carbohydrate and lipid metabolism and neurological status in patients with type 2 diabetes mellitus (DM) and diabetic neuropathy (DN).

Materials and methods. Seventy-eight patients with type 2 DM and DN were examined. The first group included 58 patients who were prescribed alpha-lipoic acid drugs (Octolipen, Thioctacid, Thiogamma and Berlithion) at 600 mg/day dropwise as antihyperglycemic therapy and B group vitamins (combilipen and milgamma) at 2 mL/day with further oral intake of octolipen, thioctacid HR and berlithion at 600 mg/day and liposoluble formulations, such as combilipen tabs, milgamma compositum or benfogamma, for 12 weeks. The second group included 20 patients with type 2 DM and DN who received antihyperglycemic therapy. All of the patients were comparable in age, DM status, DN duration, body mass index and concomitant diseases. The third group (control) included 18 healthy individuals. The efficacy of therapy was determined by assessing HbA1c dynamics, glycaemic control, lipid spectrum and sensorimotor symptoms under the TSS and NIS-LL scales; measuring pain levels with the McGill Pain Questionnaire and visual analogue scale (VAS); and performing stimulation electroneuromyography of n. tibialis and n. peroneus to analyse M-wave characteristics, nerve conduction velocity (NCV) and residual latency (RL). All analyses were performed before the administration of combined therapy and at the completion of the 12-week treatment.

Results. Comparative analysis of the combined therapy of patients with type 2 DM and DN demonstrated an improvement in positive neurological symptomatology according to the TSS scale and reduced negative symptoms according to the NIS-LL scales as well as reductions in neuropathy symptoms according to the McGill Pain Questionnaire and trends toward M-wave growth with reduced RL and increased NCV. Furthermore, individual-targeted glycaemic control (HbA1c < 7.5%) was achieved of 78% with consistent reduction in the atherogenicity index. Correlation analysis determined an average direct link between the HbA1c level and negative neurologic manifestations on the NIS-LL scale (r = 0.42, p = 0.027) and an inverse link between the McGill Pain Questionnaire score and NCV (r = -0.36, p = 0.019).

Conclusions. The complex diagnostics of neurological changes (TSS, NIS-LL, McGill and VAS scales) allows the assessment of the severity of distal DN after combined therapy with alpha-lipoic acid drugs (600 mg) and liposoluble forms of B group vitamins. These methods are also recommended for use in outpatient settings for the early detection and prevention of the diabetic foot development.

The number of elderly persons with diabetes mellitus type 2 is expected to progressively increase. Management of this category of patients should be individualised and include the adequate correction of hyperglycaemia, prevention of long-term complications, prevention of hypoglycaemia, reduction of cardiovascular mortality and preservation of quality of life. This article summarises basic information on the pathophysiology of carbohydrate metabolism, peculiarities of the course of diabetes and use of antidiabetic drugs in the elderly. Special attention is paid to reviewing the goals of glycaemic control and proposed clinical guidelines.

Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays.

Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC).

Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5).

Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice.

 

During the past two decades, the unequivocally recommended treatment method of Type 2 diabetes mellitus was insulin administration and intensification in the earliest possible stage of the diagnosis. This approach is not only unfounded but was never scientifically proven. Yet, it has been zealously advocated to medical professionals. In fact, a sound body of evidence disproves this long-standing treatment approach. This method is a cornerstone of, what we now know to be two great illusions of past century, namely, glucocentrism and intensification. Numerous recently published studies provide alarming data regarding serious side effects of blind intensification and insulin overdosing in T2DM. They raise major concerns and call for revision of the traditional approach. Since insulin is an integral and deeply rooted part of the intensification agenda of treating T2DM, it has now suffered a serious drawback. Alternatively, in this review authors present the novel Gravicentric (Energy) concept of T2DM acceptance and therapy. They offer a new classification of anti-diabetes drugs based on their energy effect and present their Gravicentric Algorithm for wide practical utilization. For that reason, the "ELEPHANT" abbreviation was found as a helpful reminder. Viewing T2DM as disease of energy balance together with anti – energy drugs implementation provide medical doctors an unique opportunity to transform T2DM from "slowly – progressive" disease to rapidly reversible condition, which it actually is.

Yalkin Halmatovich Turakulov is an internationally known medical researcher whose name is firmly engrained into the history of national endocrinology. He headed the Pharmaceutical Medical Institute, Tashkent Medical Institute, Regional Institute of Medicine, Institute of Nuclear Physics of Uzbekistan Academy of Sciences, Institute of Biochemistry and others institutions various times and was involved in the establishment of many of them. He was a teacher to many doctors and scientists. This article presents his biography and describes his impact on national and world science.