ITGA2 Gene Polymorphism Is Associated with Type 2 Diabetes Mellitus in the Kazakhstan Population.

Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (-2549I/D), RAGE (-429T/C and -374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case-control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII- allele was associated with diabetes: OR = 1.81 [1.09-2.99] for DR patients, and OR = 2.24 [1.34-3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII- allele, and not the minor BglII+, which is considered as risky for DR.

The first experience of using a comprehensive detailed ultrasound examination of the foot in patients with diabetes mellitus.

INTRODUCTION: Assessment of amputation risk has been discussed more than once in the management of patients with diabetes. Systemic inflammatory symptoms can serve as signs of an infectious process. However, not all patients show exhibit these symptoms in a timely manner. At the same time, a decrease in pain, tactile and temperature sensitivity fails as a part of the main assessment of risk factors in diabetes mellitus. METHODS: Using examination methods and comparing with clinical experience and the results of other researchers, a pilot study was carried out to diagnose structural changes in the foot in patients with diabetes. Nested examinations were carried out in several stages, on the expert class medical ultrasonographic apparatus Siemens Acuson NX3. The methods of ultrasound diagnostics in the diabetic foot can be significantly helpful when using a scale of criteria and guidelines for the examination. CONCLUSION: The main diagnostic criterion for determining the risks of developing a diabetic foot condition, could be a gradual transition from the phase of compaction of hyaline cartilage to the phase of synovitis, and then to the phase of development of bone tissue necrosis related to a part of the Charcot's foot. It leads to disruption of the musculoskeletal system of the foot, and atherosclerotic plaques and stenosis of the dorsalis pedis artery and first toe, which form a deterioration in the nutrition of the soft tissues of the foot with their necrosis.

Forecasting the Prevalence of Diabetes Mellitus Using Econometric Models.

INTRODUCTION: The prevalence of diabetes in Kazakhstan has reached epidemic proportions, and this disease is becoming a major financial burden. In this research, regression analysis methods were employed to build models for predicting the number of diabetic patients in Kazakhstan in 2019, as this should aid the costing and policy-making performed by medical institutions and governmental offices regarding diabetes prevention and treatment strategies. METHODS: A brief review of mathematical models that are potentially useful for the task of interest was performed, and the most suitable methods for building predictive models were selected. The chosen models were applied to explore the correlation between population growth and the number of patients with diabetes as well as the correlation between the increase in gross regional product and the growth in the number of patients with diabetes. Moreover, the relationship of population growth and gross domestic product with the growth in the number of patients with diabetes in Kazakhstan was determined. Our research made use of the scikit-learn library for the Python programming language and functions for regression analysis built into the Microsoft Excel software. RESULTS: The predictive models indicated that the prevalence of diabetes in Kazakhstan will increase in 2019. CONCLUSION: Mathematical models were used to find patterns in a comprehensive statistical dataset on registered diabetes patients in Kazakhstan over the last 15 years, and these patterns were then used to build models that can accurately predict the prevalence of diabetes in Kazakhstan.

BE-SMART (Basal Early Strategies to Maximize HbA1c Reduction with Oral Therapy): Expert Opinion.

The past three decades have seen a quadruple rise in the number of people affected by diabetes mellitus worldwide, with the disease being the ninth major cause of mortality. Type 2 diabetes mellitus (T2DM) often remains undiagnosed for several years due to its asymptomatic nature during the initial stages. In India, 70% of diagnosed diabetes cases remain uncontrolled. Current guidelines endorse the initiation of insulin early in the course of the disease, specifically in patients with HbA1c > 10%, as the use of oral agents alone is unlikely to achieve glycemic targets. Early insulin initiation and optimization of glycemic control using insulin titration algorithms and patient empowerment can facilitate the effective management of uncontrolled diabetes. Early glucose control has sustained benefits in people with diabetes. However, insulin initiation, dose adjustment, and the need to repeatedly assess blood glucose levels are often perplexing for both physicians and patients, and there are misconceptions and concerns regarding its use. Hence, an early transition to insulin and ideal intensification of treatment may aid in delaying the onset of diabetes complications. This opinion statement was formulated by an expert panel on the basis of existing guidelines, clinical experience, and economic and cultural contexts. The statement stresses the timely and appropriate use of basal insulin in T2DM. It focuses on the seven vital Ts-treatment initiation, timing of administration, transportation and storage, technique of administration, targets for titration, tablets, and tools for monitoring.Funding: Sanofi.

Thoughts, Words, Action: The Alma-Ata Declaration to Diabetes Care Transformation.

The International Conference on Primary Health Care, held at Alma-Ata, present-day Kazakhstan, in September 1978, was a landmark in global health care. The Declaration of Alma-Ata that was adopted at that conference successfully refocused attention and energy on primary health care. In a similar manner, the United Nations resolution of 2006 highlighted the dangers of the diabetes pandemic. The underlying philosophy of the Declaration of Alma-Ata is assessed in this editorial, to determine whether it remains relevant for modern and future diabetes care. We highlight the concordance between the Declaration of Alma-Ata and the principles of present-day diabetes care, and come to the conclusion that the 1978 document is relevant for the management of the diabetes pandemic.

Consensus Recommendations on Sulfonylurea and Sulfonylurea Combinations in the Management of Type 2 Diabetes Mellitus - International Task Force.

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

Clinical implications of pre-operative rapid BRAF analysis for papillary thyroid cancer.

The activating point mutation of the BRAF gene, BRAF(T1799A), is the most common and specific genetic alteration in adult papillary thyroid carcinoma (PTC) and a possible marker of malignant potential of PTC. We have applied the PCR-RFLP method using fine-needle aspiration biopsy samples not only to our clinical practice but also to the international medical assistance effort around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy-seven cases (100 nodules) from Japan and 131 cases (137 nodules) from Kazakhstan were examined. There were 14 Japanese and 76 Kazakhstani cases of cytological malignant tumors from the examined samples. We detected 12 (85.7% of PTC) and 19 (25% of PTC) cases with BRAF(T1799A) among the Japanese and Kazakhstani cases, respectively. Of these cases, we found mutations in one cytologically "suspicious" case and even in two pathologically "benign" cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those three, were confirmed as PTC by careful pathological examination, including immunohistochemical analysis. In summary, our PCR-RFLP method for BRAF(T1799A) detection using FNAB samples is useful not only for preoperative diagnosis of PTC but also as a complementary diagnostic tool for accurate pathological diagnosis, even after surgery.