In recent years, in molecular biology there has been a shift in priorities towards deciphering the mechanisms of realization of genetic information. As a result, research has come to the fore regarding the transmission of signals between cells and within each cell.

The development of diabetes is preceded by a number of stages of impaired carbohydrate tolerance. From the state of normal through the stage of impaired glucose tolerance, the development of type 2 diabetes mellitus, diabetes complications, the disease leads to death. With this understanding of the disease, the question arises: is it possible to prevent diabetes and its complications? With regard to type 2 diabetes, the answer is yes. Primary disease prevention involves exposure before the onset of the disease; the presence of a specific target, i.e., an etiological determinant; continued effect after discontinuation of therapy.
The results of many studies have been published, which convincingly proved that drug and non-drug effects can prevent the transition of the stage of impaired glucose tolerance into diabetes mellitus.

The term "cardiorenal syndrome" means the development of pathology of the cardiovascular system, causally associated with kidney damage. The role of kidney pathology as an independent risk factor in the development and progression of atherosclerosis has been intensively discussed only in the last 10 years, and therefore the term "cardiorenal" or "nephrocardial" syndrome has also appeared only in recent years. It was found that pathology of the kidneys leads to a more rapid progression of atherosclerotic vascular changes, which cannot be explained only by traditional risk factors such as arterial hypertension (AH), dyslipidemia, obesity, smoking, etc.

Early studies of the association of a large group of gene candidates indicated that only the polymorphic markers of angiotensin-converting enzyme (ACE) I gene and endothelial vascular cell NO-synthetase (NOS3) gene were associated with diabetic nephropathy (DN) in type 1 diabetes mellitus. The purpose of this study was to examine DN predisposition in patients with type 1 DM, by using the polymorphic markers of the genes of apolipoproteins Е (АРОЕ) and В (АРОВ) which encode for lipid metabolic proteins, as well as polymorphic microsatellites in the chromosomal region 3q21-q25. Two groups of patients of patients with type 1 DM with (n = 54) and without (n = 65) DN were examined to analyze the gene association with DN. Analyzing the frequencies of the alleles and genotypes of the polymorphic marker E2/E3/E4 ofAPOR gene has indicated that the carriers of the allele E3 and the genotype E3/ E3 have a higher risk for DN (OR = 2.08 and 2.16, respectively). In case of АРОВ gene, the carriers of allele I and genotype II of the polymorphic marker I/D have been ascertained to have a higher risk for DN (OR = 1.91 and 2.11, respectively) while those of allele Dhave, on the contrary, a lower risk for DN (OR = 0.52). The authors have revealed an association of a group of polymorphic microsatellites with DN in the chromosomal region 3q21-q25. There is the greatest association for the marker D31550. The carriers of allele 12 (OR = 4.85) and genotype 12/14 (OR = 6.25) have a much higher risk for DN. In all probability, in the chromosomal region 3q21-q25, there is a major gene that initiates the development of DN whereas other genes associated with DN affect the rate of its progression to a greater extent. Thus, among the Moscow Russian dwellers suffering from type 1 DM, the progression of DN is mainly associated with the genes of ACE, NOS3, APOE, and АРОВ while the major gene that determines the first stages of DN development in type 1 DM is likely to be located in the chromosomal region 3q21-q25.

Oxidative stress is an imbalance in the body between prooxidants and the antioxidant defense system, which, to varying degrees of severity, accompanies insulin deficiency or insulin resistance, which are one of the essential components of the pathogenesis of vascular complications of diabetes. 

It has been established that oxidative stress in diabetes mellitus can be the result of several mechanisms: a) increased formation of reactive oxidants that are formed during the oxidation of both carbohydrates themselves and carbohydrates complexing with various proteins, as well as the result of autooxidation of fatty acids in triglycerides, phospholipids and esters cholesterol; b) reducing the activity of the antioxidant system in the body, which is represented by glutathione, glutathione peroxidase, catalase, superoxide dismutase, vitamins, K, E and C and other antioxidants (taurine, carotene, uric acid and ubiquinol); c) disorders of enzymes of polyol glucose metabolism, mitochondrial oxidation, metabolism of prostaglandins and leukotrienes and a decrease in glyoxalase activity; d) violation of the concentration or exchange of glutathione and ions of certain metals. In addition, ischemia, hypoxia and pseudohypoxia of tissues observed in diabetes mellitus are additional factors contributing to the increased formation of reactive oxidants in various organs and tissues.

The histo- and ultrastructural characteristics ofmyocardial and vascular lesions were studied in 27 patients (15 males and 12 females) with type 2 diabetes mellitus (DM), coronary heart disease (CHD), and atherosclerosis obliterans of lower extremity vessels. The lifetime endomyocardial biopsy specimens, intraoperative leg arterial biopsy specimens taken from intact tissues during leg amputation and поп-infarction areas of the left ventricular myocardium, autoptically taken from 32 patients who had died from complications due to atherosclerosis were examined. Myocardial ultrastructural derangement in type 2 DM was found to primarily affect the structures responsible for the energy and plastic metabolism in the cardiomyocytes. Moreover, the most pronounced functional changes were associated with cardiac diastolic function. The morphological pattern of damage to endotheliocytes, working cells of the myocardium and the ultrastructural organization of microvessels in patients with type 2 DM are directly related to the severity of hormone metabolic disorders, hyperinsulinemia and hyperglycemia in particular. The changes found in the microcirculatory system in type 2 DM were pronounced to the extent that the presence of coronary artery stenoses aggravated the typical changes in the architectonics and cardiomyocytic functions no longer.

The present paper deals with the epidemiology, pathogenesis, and diagnosis of peripheral diabetic macroangiopathy. A total of 102 patients (51 males and 51 females) aged 45 to 74 years (mean 63.4 ± 4.0years) who had type 2 diabetes mellitus (DM) and clinical manifestations of coronary heart disease (CHD) were examined to study endothelial function and the degree and extent ofocclusive lesions in the lower extremity arteries in the neuropathic and neuroischemic forms of the diabetic foot. The study of endothelial function in the reactive hyperemia test demonstrated a significant reduction inflow-dependent vasodilatation in all the examined patients with type 2 DM and CHD as compared with gender- and age-matched CHD patients without carbohydrate metabolic disorders. This is mostly characteristic for patients with type 2 DM, CHD, and femoropopliteal atherosclerosis who showed a 2-fold decrease in flow-dependent vasodilatation as compared with the control patients. Endothelial function more significantly impaired as the severity and extent of diabetic macroangiopathy increased.

Adequate leg unloading is a key factor of healing of trophic ulcers of the diabetic foot (DF). Total contact casting (TCC) is a method that has recently been used in clinical practice. A study was conducted to examine the effectiveness and safety of TCC versus conventional leg unloading methods, which included 27 patients with the neuropathic DF. TCC and conventional unloading methods ("a low shoe", bed confinement) were used in 14 (Group 1) and 13 (Group 2) patients, respectively. There were no significant differences between the groups in age, gender, the duration and type of diabetes mellitus, and the duration of ulcers. However, in Group 1, trophic ulcers are larger and more frequently located in the middle and posterior parts of the foot (which hampers its unloading). During 6-month therapy, 73 and 46% of the ulcers healed in Groups 1 and 2, respectively. Despite the larger sizes of ulcers in Group 1, the healing time did not virtually differ (109 and 111 days, respectively). Thus, TCC was more effective than conventional unloading methods. Slower trophic ulcer healing in the presence of inadequate unloading more commonly caused severe complications that total contact cast wearing.

A screening of patients with diabetes mellitus (DM) at a high risk for trophic foot ulcers and amputation has been made in Saint Petersburg since 2001. This study was undertaken to analyze the results of this screening. A total of 3807 patients with DM (96% with type 2 and 4% with type 1) were examined. The history of DM was 9.6 ±8.1 years; the body mass index, 30.4±8.2 kg/m²; mean age, 66.5±10.9 years. Passport data, the year of detection of DM, its type, anthropometric indices, history data on ulcerative defect of the foot and/or amputation were recorded. Arterial pulsation in both feet, sensitivity to 10-g monofilament; the presence of foot or toe deformities were assessed. The risk was determined in accordance with the modified recommendations of the International Agreement on the Diabetic Foot. Low, intermediate, and high, and very high risks were detected in 43.1, 37.3, 14.6%, and 5% of the examinees, respectively. The groups did not differ in age, but the patients at a very high risk had a long history of DM as compared with those at a low risk (14.9 ±9.1 versus 8.4 ± 7.7years; p <0.05). Foot deformity, severe polyneuropathy, lower extremity angiopathy were identified in 46, 11.5, and 10.6% of the patients, respectively. Foot and toe deformities were more frequently detected in type 1 DM. The substantially long persistence of DM was a cause of the high incidence of polyneuropathy, angiopathy, and a history of pyonecrotic processes in patients with type 1 DM. The proportion of patients at high and very high risks was almost 20%, which indicates that Diabetic Foot rooms should be set up. In the examinees, foot and toe deformities are the most common risk factors, which is largely due to the age of the population. The results of screening suggest that it is necessary to set up additional Diabetic Foot rooms, their work being aimed at foot care, and, in terms of the great spread of food deformity, to review the orthopedic provision system for diabetic patients.

The paper presents the results of a prospective (13-year) study of the effectiveness of a diabetes teaching and treatment program (DTTP) for patients with type 1 diabetes mellitus. The patients were divided into two subgroups according to the frequency of follow-up visits to the Endocrinology Research Center, Russian Academy of Medical Sciences. The intensive follow-up subgroup comprised the patients who had visited the center at least every 4-6 months after DTTP (Group 1). These visits had included regular measure-ments of the level of HbA_1c; recommendations on insulin dosage adjustment regimens; discussion of the results of glycemia self-monitoring according to the patient's diabetes diary, etc. The other subgroup consisted of the patients who were followed up only in the urban health care system. The baseline compensation of carbohydrate metabolism was poor. Subgroup analysis of the changes in the level of HbA_1c indicated that Group 1 patients had its significantly lower levels 7 and 13 years after DTTP. There was an inverse correlation between the level of HbA_1c and the rate of glycemia self-monitoring. The study demonstrated the high effectiveness of DTTP in reducing the incidence of acute and chronic complications of diabetes mellitus, the number of hospital admissions for diabetes and sick leave days throughout the follow-up.

On July 24, 2004, we have lost the one of the leading figures in Russian endocrinology — G.S. Zefirova — an outstanding endocrinologist, a brilliant clinician, scientist and teacher who raised several generations of endocrinologists. She worked for more than 40 years as an assistant professor at the Department of Endocrinology and Diabetology of the Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation (the former Central Institute for the Advancement of Doctors).