Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

[A 20-year prospective follow-up study to evaluate the development of retinopathy and nephropathy after the onset of type 1 diabetes mellitus: Contribution of glycemic control and metabolic memory]. / Prospektivnoe 20-letnee nabliudenie, otsenivaiushchee razvitie retinopatii i nefropatii ot momenta debiuta sakharnogo diabeta 1-go tipa: vklad kontrolia glikemii i 'metabolicheskoi pamiati'.

AIM: To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). SUBJECTS AND METHODS: A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. RESULTS: During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. CONCLUSION: The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

[Evaluation of markers for renal graft dysfunction in patients with type 1 diabetes mellitus after kidney transplantation and simultaneous pancreas-kidney transplantation]. / Otsenka markerov disfunktsii pochechnogo transplantata u patsientov s sakharnym diabetom 1-go tipa posle transplantatsii pochki i sochetannoi transplantatsii pochki i podzheludochnoi zhelezy.

AIM: To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). SUBJECTS AND METHODS: The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-ß1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. RESULTS: The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=-0.36; p<0.05) and positively with the level of albuminuria (r=0.40; p<0.05). There was also a direct correlation of urinary podocin concentrations with blood creatinine levels (r=0.35; p<0.05) and that of NGAL with albuminuria (r=0.35; p<0.05) in recipients after transplantation. CONCLUSION: The high levels of biomarkers for kidney graft dysfunction in the examinees (including subjects after SPKT) reflect the persistence of graft microstructural injuries in clinically stable function.

[Association of the polymorphisms of the FTO, KCNJ11, SLC30A8 and CDKN2B genes with type 2 diabetes].

To study the association with diabetes mellitus type 2 we performed anal- ysis of the distribution of frequencies of alleles and genotypes of polymorphic markers of FTO, KCNJ11, SIC30A8 and CDKN2B genes. The study included groups of T2DM patients and unrelated controls of Russian origin. Analysis of the distribution of frequencies of alleles and genotypes of the polymorphic markers of KCNJ11, SLC30A8 and CDKN2B genes showed the presence of association with T2DM in Russian population, while for the FTO gene was not found statistically significant associations with type 2 diabetes. We can conclude that in Russian population main role in the development of type 2 diabetes play genes, affecting the level of syn- thesis and secretion of the insulin in beta-cells of the pancreas.

[Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease]. / Neglikemicheskie effekty inkretinov u patsientov s dlitel'nym techeniem sakharnogo diabeta 1-go tipa i khronicheskoi bolezn'yu pochek.

AIM: To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. MATERIAL AND METHODS: Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-ß, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification. RESULTS: The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=-0,320; p<0.05) and the magnitude of coronary artery calcification (CI: r=-0.308; p<0.05). GIP showed a differently directed effect on the proinflammatory factors: fibrinogen (r=-0.264; p<0.05), CRP (r=-0.626; p<0.05), and FGF-23 (r=-0.341; p<0.05). CONCLUSION: The investigation has demonstrated the nonglycemic effects of incretins that favorably affect the pathogenetic processes underlying the late complications of DM1. The findings point to the potential efficacy of incretin-based drugs in preventing and treating the late complications of DM, which necessitates the conduction of larger investigations.

[Risk factors for and prognostic value of multifocal atherosclerosis in patients with diabetes mellitus].

AIM: To study the prognostic value of multifocal atherosclerosis (MFA) in patients with diabetes mellitus (DM) at high risk for myocardial ischemia who need coronary angiography (CAG). SUBJECTS AND METHODS: The investigation included 148 patients: 25 with type 1 DM (DM1), 73 with type 2 DM (DM2), and 50 without DM who had undergone CAG. Duplex ultrasound scanning of lower limb vessels and brachiocephalic and renal arteries was carried out in all the patients. RESULTS: Involvement of two or more vascular beds was noted in 60% of the patients with DM1, in 68.4% of those with DM2, and in 34% of those without DM (p < 0.05). Regression analysis showed that the risk factors of MFA were defined to be myocardial infarction (MI) in the history (OR=2.4; p=0.02), DM (OR=3.9; p=0.0002), smoking (OR=2.4; p=0.05), elevated creatinine (OR=6.5; p=0.002) and fibrinogen (OR=6.8, p=0.004) levels. Among the DM patients, there were 26.5% of those who had achieved a main assessment criterion (a combined end point (CEP)), such as death, urgent hospitalization for heart failure, nonfatal MI, nonfatal stroke, lower extremity amputation, double creatinine levels, and achievement of end-stage renal failure during a 24-month follow-up. In patients without carbohydrate metabolic disturbances, this indicator was 12% (p=0.01). During the prospective study, a total of 6.1% of patients died in the DM group; all the patients in the non-DM group completed the study. Calculation of survival rates by the Kaplan-Meier method indicated that the DM patients with concurrent atherosclerotic lesion had achieved CEP significantly more frequently than the comparison group. Such differences were absent among the persons without carbohydrate metabolic disturbances. CONCLUSION: The regression analysis has shown that prior MI, DM, smoking, creatinine and fibrinogen levels are factors associated with the development of MFA in the examined groups. In the patients with DM, concurrent atherosclerosis of two or more vascular beds is an important factor for the progression of cardiovascular and renal diseases.

[Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

AIM: To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). MATERIAL: 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. METHODS: All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. RESULTS: Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression model identified diabetes, reduced renal function, previous myocardial infarction, smoking, ADMA and fibrinogen as factors associated with presence of multifocal atherosclerosis. CONCLUSION: Coexistence of atherosclerosis in two or more vascular beds was more frequent in P with diabetes and hemodynamically significant CA atherosclerosis than in PWD. It was associated with renal and cardiac dysfunction, excessive activation of mediators of inflammation, hemostasis, and factors of endothelial damage.

[Renal artery stenosis in patients with type 2 diabetes mellitus: clinical signs, diagnosis, prognostic value].

AIM: To define the prevalence, clinical features, risk factors, and prognostic value of atherosclerotic renal artery stenosis (RAS) in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: One hundred and fifty-seven T2DM patients (63 males and 94 females) aged over 50 years were examined. Screening for RAS was carried out by duplex ultrasound scanning (DUSS); the diagnosis was verified by multispiral computed tomography and magnetic resonance imaging. Moreover, the detection rate of RAS was analyzed from the selective angiographic readings of 30 patients with T2DM and 26 coronary angiography patients without DM who had undergone coronary angiography (CA). RESULTS: In the total group of T2DM patients, the RAS detection rate was 36.9%, as evidenced by DUSS and 43.3% by selective renal artery angiography in the patients who had undergone CA. The factors associated with the development of RAS were smoking (relative risk (RR) = 3.3; p < 0.001); atherosclerosis of coronary (RR = 4.28; p < 0.001) and peripheral (RR = 3.38; p < 0.02) arteries, isolated systolic hypertension (RR = 3.9; p < 0.01), and anemia (RR = 6.4; p < 0.001). In patients with T2DM, RAS was one of the important factors of progressive renal and cardiac diseases and increased mortality determined by the combined end point: death, emergency hospitalization for heart failure, myocardial infarction, double creatinine, and end-stage renal failure (RR = 6.28; p < 0.001). CONCLUSION: The optimization of prognosis in T2DM patients with RAS requires its timely clinical identification in combination with other types of renal lesion, aggressive correction of the mechanisms of the progressive process, and development of medical and endovascular therapies.

[Contrast-induced nephropathy in coronarography of patients with type 2 diabetes mellitus: risk factors, prognostic significance, prophylactic approaches].

AIM: To determine risk factors, prognostic implications and prophylaxis of contrast-inducible nephropathy (CIN) during coronarography (CG) in patients with type 2 diabetes mellitus (DM). MATERIAL AND METHODS: Records for 151 patients with type 2 DM and 50 non-diabetic patients examined with CG in A.N. Bakulev Research Center for Cardiovascular Surgery in 2000-2007 were analysed retrospectively. All the patients have undergone clinical examination including tests for blood serum creatinine before and after 48 hours after CG, standard ECG and echocardiography. Glomerular filtration rate was estimated by MDRD formula. Selective CG was made with application of contrast agent Omnipak-300 (iohexol). RESULTS: CIN after CG more frequently developed in diabetics than in non-diabetic patients matched for age, renal function, dose of contrast medium and hydration regime (40.4 and 16%, respectively; p < 0.002). Risk of CIN in patients with type 2 DM was associated with cardiac failure of NYHA class III-IV, anemia, dose of the contrast agent, intake of diuretic drugs before and after the procedure, multiple affection of the coronary vessels, necessity of intervention. Patients with type 2 DM and CIN showed more rapid decline of the renal function, more frequently developed severe cardiovascular events, had worse 1-year survival. CONCLUSION: High probability of CIN and its prognostic significance in type 2 DM patients necessitates assessment of an individual risk for taking preventive measures during conduction of contrast diagnostic procedures.

[Anemia in diabetic nephropathy: prevalence, clinical and pathophysiological aspects].

AIM: To investigate detectability of anemia, its clinical and pathophysiological features in patients with diabetic nephropathy (DN). MATERIAL AND METHODS: The trial included 1020 patients with type 1 and 2 diabetes mellitus (DM). DN was diagnosed in 50% of them. Incidence of anemia was compared in 92 DN patients in type 1 DM and in 230 patients with chronic glomerulonephritis (CGN). Concentration of erythropoietin (EP) in blood serum was measured in 94 DN patients in type 1 and 2 DM. RESULTS: Anemia develops in type 1 and 2 DM patients free of DN and unaffected renal filtration function (glomerular filtration rate--GFR > 60 ml/min 1.73 m2) was 23.3 and 18.3%, respectively. In DN patients incidence rate of anemia depended on GFR and increased with growing severity of renal failure reaching 85.7% in GFR < 30 ml/min/1.73 m2. Development of anemia in DN depended also on protein urine excretion (20.0% in normoalbuminuria, 25.7% in microalbuminuria and 48.2% in proteinuria). Anemia in DN was detected more frequently and was more severe (by hemoglobin reduction) than anemia in CGN in equal GFR. At all stages of chronic disease of the kidneys EP secretion was low normal and independent of Hb and GFR. CONCLUSION: In DN anemia occurs more often and is more severe than in CGN. Anemia results from inadequate production of EP by the kidneys in response to anemia. Thus, early start of its correction is necessary for improvement of quality of life and inhibition of progression of micro- and macrovascular complications of DM.

[Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus].

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and n = 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker epsilon2/epsilon3/epsilon4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele epsilon3 and genotype epsilon3/epsilon3 of the polymorphic marker epsilon2/epsilon3/epsilon4 of APOE gene as well as in the carriers of allele 1 and APOB genotype/gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.

[A search for association between the polymorphic markers of PON1 and PON2 genes and diabetic nephropathy in patients with type I diabetes mellitus].

Alleles and genotypes of polymorphic markers of paraoxonase 1 and paraoxonase 2 genes (PON1 and PON2) encoding enzymes of the body antioxidative defense were compared in type 1 diabetes mellitus patients with or without diabetic nephropathy. The patients with nonoverlapping ("polar") phenotypes constituted different groups. The first group contained patients with diabetic nephropathy (DN+, n = 62), clinical proteinuria (albuminuria above 300 mg per day), and at least 15-year disease duration. In control group, the patients had no diabetic nephropathy (DN-, n = 68), their albuminuria was below 200 mg per day, and disease duration was at least 20 years. Comparative analysis with exact Fisher's test revealed no significant differences in frequencies of alleles and genotypes of the PON1 gene polymorphic marker Gln192Arg and of PON2 gene polymorphic markers Ala148Gly and Cys311Ser. Our results suggest that the polymorphic markers studied are not associated with diabetic nephropathy among Russian patients in Moscow.

[Associative analysis of the connection between mutation C1167T in the catalase gene and polymorphic marker D6S392 nearby the Mn-dependent superoxide dismutase gene with diabetic microangiopathies]. / Assotsiativnyi analiz sviazi mutatsii C1167T v gene katalazy i polimorfnogo markera D6S392 riadom s genom Mn-zavisimoi superoksiddismutazy s diabeticheskimi mikroangiopatiiami.

AIM: To study allele polymorphism of two variable regions [C1167T substitution in the catalase (CAT) gene D6S392 microsatellite near the Mn-dependent superoxide dismutase (SOD2) gene] was studied in insulin-dependent diabetic (IDDM) patients with (n = 36) or without (n = 56) diabetic nephropathy, and with (n = 30) or without (n = 44) diabetic retinopathy. MATERIAL AND METHODS: Both polymorphic regions were amplified using polymerase chain reaction (PCR). PCR products were separated using polyacrylamide (D6S366) or agarose (C1167T) gel electrophoresis. In a case of C1167, PCR-amplified products were digested with BstXI restriction endonuclease before electrophoresis. A significance of the difference between allele distributions in complicated and uncomplicated IDDM patients was estimated using the exact Fisher's test. RESULTS: No significant difference was observed in allele and genotype frequencies in complicated and uncomplicated IDDM subjects. CONCLUSION: C1167 polymorphism in the CAT gene and D6S366 near the SOD2 gene are not associated with the development of diabetic nephropathy and diabetic retinopathy in IDDM.

[Identification of the locus associated with diabetic nephropathy in type 1 diabetes mellitus]. / Identifikatsiia lokusa assotsiirovannogo s diabeticheskoi nefropatiei pri sakharnom diabete tipa 1.

Polymorphic tetranucleotide microsatellites D3S1512, D3S1744, D3S1550, and D3S232 were used to study the association of chromosome region 3q21-q25 neighboring the angiotensin II receptor type 1 gene (AT2R1) with diabetic nephropathy (DN) in diabetes mellitus type 1 (DM1). Allele and genotype frequencies were compared for DM1 patients with (N = 39) or without (N = 62) DN. Fisher's exact test with Bonferroni's correction revealed significant differences in frequencies of two D3S2326 alleles, one D3S1512 allele, and one allele and one genotype of D3S1550. No significant difference was observed with D3S1744. Thus, region 3q21-q25 proved tightly associated with DN in ethnic Russians with DM1 from Moscow.

[Polymorphism of gene encoding vascular angiotensin II receptor and microangiopathies in patients with insulin-dependent diabetes mellitus]. / Polimorfizm gena sosudistogo receptora angiotenzina II i mikroangiopatii pri insulinzavisimom sakharnom diabete.

Polymorphism A1166C of the AT1R gene encoding angiotensin vascular receptor [replacement of C (cytosine) for A (adenine)) at position 1166] was compared in patients with insulin-dependent diabetes mellitus (IDDM) complicated by diabetic nephropathy (DN) and in noncomplicated patients (n = 27 and n = 41, respectively) and also in patients with IDDM complicated by diabetic retinopathy (DR) and in correspondent noncomplicated individuals (n = 30 and n = 44, respectively). The frequency of AT1R gene alleles and genotypes in patients with IDDM complicated by DN did not differ significantly from that observed in patients with noncomplicated IDDM. In contrast, in patients with IDDM complicated by retinopathy, a significant decrease in the content of A allele (68.3% against 82.6%) and a significant increase in the content of C allele (31.7% against 17.4%) was found as compared with the control group. Thus, in the Moscow population, A1166C polymorphism of the AT1R gene is not associated with diabetic renal complications but indeed associated with diabetic retinal complications. C allele is a risk factor of DR (the relative risk, RR, is equal to 2.17), and A allele is, in contrast, a protective factor against early retinopathy development (RR is equal to 0.49).

[Diabetic nephropathy: risk factors of rapid progression of renal failure]. / Diabeticheskaia nefropatiia: faktory riska bystrogo progressirovaniia pochechnoi nedostatochnosti.

AIM: To reveal factors accelerating development of chronic renal failure (CRF) in patients with insulin-dependent diabetes mellitus type I (DM-I). MATERIALS AND METHODS: A retrospective analysis of case histories was made for 40 patients with DM-I exhibiting progression of proteinuric stage of diabetic nephropathy prior to CRF stage. Clinical-laboratory indices were compared for patients with slow (group 1, n = 17) and fast (group 2, n = 23) development of CRF. RESULTS: Patients of group 2 had significantly higher levels of glycosylated hemoglobin, total cholesterol, triglycerides in the blood, urine protein excretion, systolic and diastolic blood pressure than patients of group 1. Also, patients of group 2 had not taken antihypertensive drugs regularly. CONCLUSION: Factors of risk of CRF early development of DM-I patients comprise unsatisfactory compensation of carbohydrate metabolism, hyperlipidemia, high proteinuria, arterial hypertension and inadequate antihypertensive therapy.

[Effect of azathioprine on immunologic parameters in patients with newly diagnosed insulin-dependent diabetes mellitus]. / Vliianie azatioprina na immunologicheskie pokazateli u bol'nykh s vpervye vyiavlennym insulinzavisimym sakharnym diabetom.

Azathioprine immunosuppressive therapy prolongs remissions and stimulates residual beta-cell function, suppresses insulin antibody production, reduces the activity of the complement and CH50 components, reduces initially increased cellular immunity parameters (total T and B cell counts, T helper to T inductor ratio, and the count of DR carrier cells) in patients with newly detected insulin-dependent diabetes mellitus; this makes this drug effective at the first stages of the disease. When selecting patients for immunosuppressive therapy the following immunity parameters should be examined: complement status, total counts of T and B lymphocytes, T-helper-inductor/T-suppressor-cytotoxic immunoregulation index, DR carrier cell counts. Reduced levels thereof are a contraindication against immunosuppressant therapy. Male patients with insulin-dependent diabetes mellitus debut at the age of over 25 are particularly susceptible to immunosuppressive therapy with azathioprine.