[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.

[Use of human insulin analogues in young patients with type 1 diabetes mellitus: Results of the RESULT observational program on the use of insulin glargine (Lantus) in combination with insulin glulisine (Apidra) as a basal-bolus regimen]. / Primenenie analogov insulina cheloveka u patsientov molodogo vozrasta s sakharnym diabetom 1-go tipa: rezul'taty nablyudatel'noi programmy RESULT po primeneniyu insulina glargin (Lantus) v kombinatsii s insulinom glulizin (Apidra) v bazal'no-bolyusnom rezhime.

AIM: To implement in 2009-2012 the RESULT observational program on the use of insulin glargine (Lantus) in combination with insulin glulisine (Apidra) as a basal-bolus regimen in patients with type 1 diabetes mellitus (DM) to evaluate the efficiency and safety of therapy with human insulin analogues. MATERIAL AND METHODS: The program covered 100 patients aged 19 to 25 years from 7 regions of the Russian Federation, who had had DM onset at the age of 9-13 years, were using human recombinant insulins as continuous insulin therapy, and had glycated hemoglobin (HbA1c) levels of 7 to 9%. The main inclusion criterion was switching to insulin therapy with the human insulin analogues Lantus and Apidra. RESULTS: A total 41 men and 59 women were followed up. Their mean baseline HbA1c level was 8.3±0.7%. After 24 months of therapy, HbA1c was significantly decreased to 7.7±0.7%; its change compared with that at Visit 1 was -0.6±0.6% (p<0.001). There was a significant reduction in fasting and postprandial blood glucose levels at 3 months of a follow-up. The number of symptomatic and asymptomatic glycemic episodes declined. No nocturnal or severe hypoglycemic episodes were recorded at 24 months of therapy. Microvascular complications did not progress during the follow-up. CONCLUSION: The use of human insulin analogues is effective and safe in treating young diabetic patients, improves their quality of life and confers no risk of asymptomatic or nocturnal hypoglycemic states.

[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.

[Elevated level of methylated catecholamine derivatives is a pathognomic laboratory sign of pheochromocytoma].

The levels of the methylated catecholamine derivatives (MCD) metanephrine and normetanephrine were measured in 46 patients operated on. The patients were divided into 2 groups: 1) 24 patients in whom chromaffinoma was histologically detected; their age varied from 9 to 75 years (mean 37.8 years); 2) 22 patients who had undergone adrenal cortical tumors or retroperitoneal tumors of extraadrenal genesis; their age ranged from 11 to 67 years (mean 44.3 years). In this group of patients, a histological study revealed aldosteromas in 7 cases, hormonally inactive adrenal cortical adenomas in 6, adrenocortical carcinoma in 5, corticosteroma in 1, adrenal lymphosarcoma in 1, adrenolypoma in 1, and renal cancer in 1. In all the patients from Group 1, there was an increase of one MCD index for instance of less than 110% of the upper normal range. The average excess of MCD levels over the upper normal range is 456% for metanephrine and 574% for normetanephrine. No increase in the level of daily MCD excretion was found in 21 out of the 22 Group 2 patients with nonchromaffin adrenal and retroperitoneal tumors. In this group, 1 patient with histologically verified mixed-cell adenocarcinoma of the adrenal cortex was observed to have a daily metanephrlne excretion increase by 17% above the upper reference range. Thus, the sensitivity of the method was 100%; its specificity was 95.5%. The lower confidence diagnostic interval for the values of daily MCD excretion was 714 ng/day for metanephrlne and 1500 ng/day for normetanephrine. The procedure for determining free MCD in plasma has a high sensitivity and specificity and may be once used as a screening for the symptomatic nature of disease in patients with arterial hypertension.