[The lipid spectrum of erythrocyte membranes in children with diabetes mellitus].

The present study was undertaken to examine the lipid spectrum of erythrocytic membranes and serum in children and adolescents with type 1 diabetes mellitus (DM-1) during pathogenetic therapy in relation to the duration of the disease, its severity, and the presence of vascular events. Ninety-nine patients with DM-1 and 40 healthy children of the same age were examined. The patients were on basic bolus insulin therapy. In children, DM-1 was ascertained to be accompanied by not only atherogenic serum lipid metabolic disturbances (the elevated levels of total cholesterol, triglycerides, low- and very low-density lipoprotein cholesterol), but also by the impaired lipid spectrum of erythrocytic membranes (reductions in the level of total lipids and the fraction of phosphatidylcholine (PC) with an increase in the level of fractions of tysophosphatidylcholine and phosphaUdylinositol; elevated levels of saturated fatty acids and decreased levels of unsaturated fatty acids in the fractions of PC and phosphatidylethanolamlne; the enhanced microviscosity of deep membranous layers and the modified outer membranous ones). Complex basic therapy resulted in incomplete normalization of the study parameters of the lipid spectrum of serum and erythrocytic membranes in DM complicated by microangiopathies, which requires optimization of conventional therapeutic regimens.

[Platelet membrane pathology in vascular complications of type 1 diabetes mellitus].

The purpose of the present study was to define a role of the impaired structural and functional organization of the platelet membrane in the mechanisms of development and progression of vascular complications of type 1 diabetes mellitus (DM). Seventy-seven type 1 DM patients (34 males and 23 females) with different stages of diabetic retinopathy and nephropathy, whose age was 18 to 55 years, were examined. Tlie patients with type 1 DM were found to have pronounced membranous structural and functional changes in the platelets (the increased microviscosity of a lipid phase, the inhibited activity of Na+,K+-ATPase), whose degree correlates with that of vascular complications. Platelet membranous structural and functional impairments are most marked in the phase of decompensation of type 1 DM. Knowledge of the pathogenetic bases of changes in the mlcrorheologlcal properties of blood cells in diabetic microangiopathies permits the use of membrane-stabilizing agents for their correction.

[Relationship of the I/D-polymorphism of the ACE gene and the T174M-polymorphism of the AGT gene to diabetic microangiopathies in children and adolescents].

The purpose of the study was to examine a role of candidate genes of the renin-angiotensin system in the development of microangiopathies in children and adolescents with type 1 diabetes mellitus (DM) and to systematize the risk factors of development of diabetic microangiopathies in order to substantiate the optimal approaches to prevention and therapeutic correction. A hundred and thirty-eight children (73 boys and 65 girls) with type 1 DM were examined. Their mean age was 13.2±0.3 years. Based on the findings, it may be assumed that patients with type DM who are the carriers of the D allele are genetically predisposed to the development of diabetic nephropathy. An association of the ID polymorphism of the ACE gene with the development of diabetic nephropathy was established in children with type 1 DM in the Siberian population. Allele I of the ACE gene ACE less frequently occurs in DM patients with nephropathy (p > 0.05) and a factor that reduces the risk of its development. The association of the D allele with the development of diabetic nephropathy suggests that the polymorphism of the ACE gene contributes to the regulation of generation of angiotensin-converting enzyme that plays an important role in the pathogenesis of this complication. There was no association of the polymorphism in question with the concomitance of diabetic nephro- and retinopathy in the patient. Analysis of the associations of the T174M polymorphism of the AGT gene with diabetic microangiopathies revealed no statistically significant differences when the distribution of the AGT gene was compared in the groups of patients with and without microangiopathies. There was an association of the T allele of the AGT gene with Type 1 DM, as evidenced by a negative TDT test in with healthy sibs. An association of the T allele with diabetic nephropathy was also ascertained.

[The genetic and biochemical mechanisms of the development of diabetic nephropathy in children].

The mechanisms responsible for the development of microangiopathies in type diabetes mellitus (DM1) are complex and under extensive study. Fresh data on the pathogenesis of DM1 make it possible to direct actual ways to the studies aimed at preventing the complications of this disease. The purpose of this study was to examine the contribution of the polymorphic types of the VNTR polymorphism of endothelial NO-synthase gene (NOS3) and the I/D polymorphism of angiotensin-converting enzyme (ACE), the status of the proteolytic systems and lipid metabolic disturbances to the development of diabetic neuropathy (DN). A total of 197 children Работа выполнена при финансовой поддержке гранта РГНФ № 00-06-00- 162а. who had DM1 in 1996-2002 were examined. Their mean age was 13.1 ±0.3 years. A control group comprised 32 apparently healthy children whose mean age was 12.8±0.1 years. DN was present in 44 children (19 boys and 25 girls). It has been established that allele A of endothelial NO-synthase is less common in diabetic patients with nephropathy (p < 0.05) and that it is a factor that reduces, while insignificantly, the risk for nephropathy (RR = 0.13). Analyzing the association with pathology by using the transmission/disequilibrium test has indicated the association of allele В of the gene NOS3 (TDT = 4.5, p - 0.034) and allele D of the gene ACE (TDT = 3.6, p < 0.05) with DN. The activity of plasma kallikrein was increased at the early stages of nephropathy (hyper-function). The higher activity of angiotensin-converting enzyme (57.0±2.9 µmol/min·l in the patients with nephropathy versus 38.1±2.8 µmol/min·/ in those without this disease) and the substantial suppression of α-proteinase inhibitor (21.1+-1.2 IU/ml in nephropathy at the stage of proteinuria versus 27.6±1.6 IU/ml without nephropathy) make a contribution to the development of nephropathy at the stages of microalbuminuria and proteinuria. ffyperlipidemia that manifests itself by the increased levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and by the decreased levels of high-density lipoprotein cholesterol is one of the mechanisms responsible for the development of DN in DM1.