The authors review results of evaluation of possibility, safety and prospects of regenerative therapy aimed at restoring beta-cell pool in diabetes mellitus. A detailed analysis of sources of new beta-cells is presented, reparation mechanisms and factors contributing to regeneration are discussed.

Diabetes mellitus detected within the first 6 months of life is termed neonatal diabetes. Two its forms, permanent and transient, differ in the durationof insulin dependence. The review contains data on mechanisms underlying this pathology and its specific clinical features.

This review was designed to evaluate prevalence, specific clinical features, and differential diagnosis of type 2 diabetes mellitus (DM2) in childrenand adolescents. Special emphasis is laid on the importance of immunological and molecular-genetic studies for the verification of diagnosis and activecase detection in h groups.

Aim.
To study dynamics of main epidemiological characteristics (incidence and prevalence) of type 1 diabetes mellitus (DM) in children in theRussian Federation (RF) and its Federal districts (FD) in 2001-2007.
Materials and methods.
Analysis of main epidemiological characteristics (incidence, prevalence, mortality) of type 1 DM in children of RF has beenunderway in the Institute of Pediatric Endocrinology, ERC, since 2001 based on results of questionnaire studies. The questionnaires regularly distributedamong Health Committees of RF subjects (primary sources of information) are designed to collect data on the size, age and sex compositionof childrens populations affected by DM1 and the number of newly diagnosed cases as per the end of each reporting year. The data obtainedare compared with those stored in the State Diabetes Registry (secondary source of information).
Results.
Major trends in the dynamics of epidemiological characteristics of type 1 DM in children of RF are similar to those worldwide. Mean annualgrowth rate is 2,8%. The incidence of DM1 remains highest in the North-West FD (15,66 per 100 000 children) followed by Central andVolga FDs (12,82 and 10,6 respectively) where its is close to the average value FDr RF (11,01). The incidence of DM1 continues to decrease in theSouthern FD (6,61% per year) and undergoes up-and-down fluctuations in Ural and Siberian FDs. It steadily grows in the Far East FD. TheNorth-South gradient of DM1 morbidity across the territory of RF has persisted during the study period.
Conclusion.
Monitoring main epidemiological characteristics of type 1 diabetes mellitus in children of RF is an integral component of the organizationof medical and preventive aid to these patients that creates a basis for predicting morbidity, planning measures for its control, and improvinggeneral quality of healthcare provided to diabetic children

Materials and methods. HLA genotyping was accomplished in 51 DM1 patients and 51 volunteers randomly selected from the indigenous populationof Yakutia (Yakuts in three successive generations). Another 205 DM1 patients and 300 healthy subjects comprised random samples of patients andcontrols respectively from residents of Moscow and Moscow region.
Results.
HLA DRB1*17(03) allele proved to be the strongest one predisposing to DM1 in the Yakutian population (relative risk, RR=8,47) andDQB1*0304 in the Moscow population (RR=8,94). The presence of DRB1*04, DRB1*17(03), DQA1*0301, DQB1*0201, and DQB1*0302 accountedfor RR >2 in both populations. Only two alleles, DRB1*04 and DRB17(03), in the Yakutian population and five of the six (DRB1*04,DRB1*17(03), DQA1*(0301), DQB1*0302, and DQB1*0304) in the Moscow one were closely associated with DM1 (RR >4). DRB1*09, DRB1*11,DQB1*13, DQB1*0602/8 in Yakutian and DRB1*11, DRB1*13, DQA1*0103, DQB1*0301, DQB1*0602/8 in Moscow populations had the highestprotective potential (RR<2). The Yakuts appear to show a broader spectrum of protective alleles. However, the study gave no definitive evidence ofthe protective role of widespread DQB1*0602/8 and DRB1*15 alleles inherent in both Russian and Finnish populations.
Conclusion.
These molecular genetic data can be of use for medicogenetic consultation to estimate the risk of DM1 in the Yakutian population.

Aim.
To analyse association of class II HLA genotype (DRB1, DQA1, DQB1) with type 1 diabetes mellitus (DM1) in an Udmurtian population.
Materials and methods.
The case-control method was applied in the study involving 29 children with DM1 and 97 age-matched healthy subjects. HLAalleles were identified by multiprimer allele-specific PCR. Association with DM1 was evaluated from the OR-odds ratio. Calculations were made usingStatSoft and STATISTICA 6 programs.
Results.
The occurrence of ?classical? highly predisposing haplotypes in the studied Udmurtian population proved significantly lower than in otherCaucasoid populations (DRB1*04-DQA1*0301-DQB1*0302 - 2,6 vs 8-16% and DRB1*17(03)-DQA*0501-DQB1*0201 - 3,6 vs 6-12,9%)trans-Encoded DQ heterodimers (DQA1*0301-DQB1*0201 and DQA1*0301-DQB1*0302) were shown to play the key role in determining the riskof DM1. They were found in 62,1% of the patients compared with 10,3% of control subjects (OR=14,2; pc=6Ч10-5).
Conclusion.
Positive DQA1*0301-DQB1*0302 or/and *0201 genotype is the most sensitive predictor of DM1 in the studied Udmurtian population.

Aim.
To analyse the degree of compensation of disturbed carbohydrate metabolism and to evaluate its effect on the prevalence of diabetic complicationsin children and adolescents from 20 regions of RF.
Materials and methods.
A total of 2984 patients with DM1 were examined in 2002-2005 including 1532 children below 14 yr and 1452 adolescentsof 15-17 yr. The patients were selected from regional DM registries by the random number method.
Results.
Mean HbA1с was 9,77?2,30%. The number of children with compensated carbohydrate metabolism at the time of screening was significantlyhigher than that of adolescents (21,1 and 15,1% respectively, p<0,01) whereas the frequency of diabetic complications in the two groups showedthe inverse trend (non-proliferative retinopathy 3,3 and 15,8, p<0,01; diabetic cataract 4,6 and 11,5%, p<0,01; microalbuminuria 10,2 and30,9%, p<0,01; distal polyneuropathy 6,9 and 15,3, p<0,01). The highest prevalence of microalbuminuria and polyneuropathy was recorded inchildren and adolescents with DM1 duration over 10 years.
Conclusion.
The relative number of children and adolescents with compensated carbohydrate metabolism was 21,1 and 15,6% respectively. The prevalenceof diabetic complications was significantly higher in the elder age group.

Aim. To elucidate the role of diabetic nephropathy in pathogenesis of myo-cardial lesions in children with type 1 diabetes mellitus from the results of dopplerography of intrarenal vessels. Materials and methods. The study involved 39 children with DM1 (mean age 12,5?2,6) divided into 2 groups. Group 1 included 12 patients with subclinical diabetic lesions in the kidneys (hyperfiltration), group 2 and 3 comprised 21 and 6 patients with diabetic neph-ropathy (microalbuminuria 30?300 mg/day or proteinuria respectively). All patients under-went standard examination to evaluate cardiovascular and vegetative nervous function. Analysis of spectrograms obtained by dopplerography of intrarenal vessels included main renal artery (MRA), segmental (SA), interlobe (ILA), arch (AA), and interlobular (ILbA) arteries. Results. The study groups were not significantly different in terms of MRA, SA, AA, and ILA hemodynamics but, unlike healthy controls, showed a nonlinear decreasing gradient in vascular resistance from MRA toward peripheral vessels especially ILA and AA. Left ven-tricular hypertrophy with disturbed diastolic performance documented in 64% of the patients correlated with microalbuminuria (r=0,56, p

Aim.
To identify factors responsible for the early development of microvascular complications in patients with type 1 diabetes mellitus (DM1)and to evaluate dependence of their prevalence on the type of insulin.
Materials and methods.
The study carried out from May 2002 to November 2007 included a random sample of patients with DM1 over 10 years in duration(n=5895, 100%, >=20 years) from the Central, Volga, Ural, Siberian, North-West and Southern federal districts. All patients underwentexamination of eye fundus and feet, measurement of microalbuminuria, creatinine, urea, serum lipid spectrum and HbА1с.
Results.
Mean HbА1с level in patients of group 1 (using insulin analogs) was significantly lower than in group 2 (using homan insulin) (Me 8,5?0,2%;9,7?0,4% SD* respectively) p>0,01. Mean daily insulin dose in group 1 and 2 was >1,0 and <=1,0 U per kg bw. Patients using human insulin analogshad few vascular and other diabetic complications than those using human insulins (p<0,05).
Conclusion.
The closest correlation between the use of insulin analogs and reduced risk of complications in group 1 was observed for nephropathy,diabetic foot, and delayed physical development.

Aim.
To evaluate variations of principal parameters of physical development in children and adolescents with type 1 diabetes.
Materials and methods.
The study included 356 children with DM1. Their height, body weight, and body mass index were compared with the respective valuesfrom percentile tables recommended by WHO and US Centre for Disease Control and Prevention. For each patient, height deviation from the mean valuewas expressed as SDS. For the assessment of physical development, the place of each parameter in one of the 7 centile intervals was determined. Harmonicityof physical development was estimated from the difference between normal intervals on the centile scale after measurement of height and body weight.Results.Most patients (55,7%) were found to harmonically develop during the 9 year-long study, 30% had excess body weight despite average height. DM1was associated with reduced SDS values for the height and parallel increase of body weight especially in the disease over 10 years in duration. The HbA_1c levelin low-height patients was significantly elevated compared with high-height ones. Negative effect of long-term metabolic decompensation on the growth of thechildren became apparent since the third year of the disease. Body weight was a more stable parameter independent of the degree of compensation.Conclusion: Children and adolescents with DM1 experience deterioration of yearly height dynamics with increasing length of the disease. Growth characteristicsare related to the degree of compensation of carbohydrate metabolism.

Aim.
To assess quality of life (QL) in children and adolescents with type 1 diabetes mellitus (DM1) depending on its duration, mode of insulin administration,and degree of social adaptation.
Materials and methods.
Generic Core Scale and Diabetes Module of Pediatric Quality of Life Questionnaire were used to estimate QL in 72 diabeticchildren and adolescents aged 5-18 yr with the participation of one of the parents. Patients with severe concomitant pathology were not includedin the study.
Results.
Overall QL score in children and adolescents with DM1 was 73,043?1,24. The psycho-social activity of most patients in all age groups was ratherhigh in contrast to suppressed physical functions due to complications of DM1 ten or more years in duration (51,4?9,19 scores). The psycho-emotionalstate was less dependent on negative effects of the disease. Patients using an insulin pump had on the whole better QL than those receiving intensiveinsulin therapy (82 and 72 points respectively, p<0,05). Patients attending a diabetes education school showed a higher degree of social adaptation.
Conclusion.
Physical functioning progressively deteriorated with the duration of DM1 whereas the psycho-emotional status of the patients was mostseriously affected in debut of the disease.

Aim.
To assess dynamics of glycated hemoglobin levels and insulin doses per kg bw in children and adolescents with poorly controlled type 1 diabetes mellitus using insulin pumps.
Materials and methods.
Retrospective analysis of HbA_1c levels and insulin doses per kg bw in children aged 2-17 years with DM1 (mean duration 5.3?3.1) before and 18 months after onset of insulin pump therapy (Medtronic Minimed 712 and 722) with a short-acting insulin analog Novopramid (Novo Nordisk) or Humalog (Ely Lilly) given to 55 (52,4%) and 50 (47,6%) of the patients respectively. НbА1с level and mean daily insulin dose per kg bw were determined when a patient visited the doctors office every 3 months.
Results.
Insulin pump therapy in patients with initially poorly controlled DM1 resulted in a decrease of HbA_1c from 9.8?0.8 to 7,8?0,5% within 18 months after its beginning (p<0,05) in the absence of severe hypoglycemia and ketoacidosis requiring hospitalization. Simultaneously, mean daily insulin requirement reduced especially in patients aged 15-18 yr (p<0,05). None of the patients wished to discontinue insulin pump therapy during the study and after its completion.
Conclusion.
Insulin pump therapy is an efficacious tool for the improvement of metabolic control in children and adolescents with poorly compensated CD1 regardless of age and duration of the disease.

Idiopathic ketosis-prone type 2 diabetes is intermediate between two major forms of diabetes mellitus. The aim of this review is to analyse factors contributingto its development and occurrence and to discuss approaches to differential diagnosis of this pathology.

Aim.
To measure stable metabolites of nitric oxide (SMNO), i.e. nitrites and nitrates, and compare the results with other biochemical characteristicsof blood in patients with type 1 and 2 diabetes mellitus (DM1 and DM2) or metabolic syndrome (MS).
Materials and methods.
The following parameters were measured in 61 patients with DM, 12 with obesity, 8 with impaired glucose tolerance (IGT),and 12 healthy subjects: blood glucose level (fasting and 2 hr postprandially), HbA_1c, insulin, C-peptide, SMNO, lipid spectrum, erythrocyte sialidaseactivity (ESA), and insulin resistance index (HOMA).
Results.
Postprandial glycemia was elevated in DM1, DM2, and IGT patients, HOMA in those with DM2 and IGT, ESA in all DM and MS patients.SMNO level was reduced in all groups especially in patients with DM and diabetic nephropathy. It negatively correlated with total cholesterol, TG,LDL, and ESA.
Conclusion.
Blood SMNO level as an indicator of endothelial dysfunction is of high diagnostic value starting from the early stages of impaired carbohydratemetabolism.

Aim.
To evaluate the risk of multiple use of BD Micro-Fine Plus insulin pen needles in terms of their contamination with microflora, pain and localreaction at the injection site.
Materials and methods.
The study included 45 patients aged above 18 yr with type 1 and 2 diabetes mellitus (DM1 and DM2) treated with shortorultrashort-acting insulins TID. Account was taken of the time each needle was used (once, for 4 and 7 days). Microbiological analysis was madeat the respective time points. Pain sensation after injection was evaluated by patients themselves using a visual-analog scale and severity of local reactionsby the physician.
Results.
Microbial growth was documented in 20 and 33,3% of the patients who used needles ones or many times respectively. Patients of the lattergroup more frequently complained of pain after injection (on day 4, p=0,08) compared with those of the former one (on day 7, p=0,03). Hyperemicfoci at injection sites developed only in case of using the same needle for 4 and 7 days (13,3 and 26,6% respectively).
Conclusion.
Multiple use of insulin pen needles by patients with DM should be avoided since it leads to hyperemia at injection sites, pain sensation,and risk of microbial contamination.

Aim.
To evaluate efficiency and safety of intensification of therapy by substituting two-phase insulin aspart 30 (DiAsp 30) for basal insulin in patients with type2 diabetes mellitus after a failure to achieve target glycemia.
Materials and methods.
Analysis of the data obtained in a group of patients involved in the PRESENT study (Physicians Routine Evaluation of Safety andEfficacy of NovoMix 30 Therapy), a 6 month-long observational study conducted in 15 countries. The subanalysis included patients previously treated with along-acting insulin analog (AB, n=34) or intermediate and long-acting human basal insulin (HB, n=3414) and transferred thereafter to DiAsp 30 therapy.End-points of efficiency were the difference between blood HbА1c and glucose (fasting and postprandial) levels measured at the onset of the study and upon itscompletion, the number of hypoglycemic episodes and adverse events, physician and patients content with the results of the treatment. End-points were consideredseparately with reference to preceding basal therapy (AB or HB).
Results.
Treatment with DiAsp 30 for 6 months resulted in a fall of HbА1c levels compared with initial values (-1,60 and -142% in AB and HB patients respectively,p<0,0001). Fasting and postprandial glucose levels also significantly decreased. The frequency of hypoglycemic episodes (number of events/patients/years) after transfer from AB therapy to DiAsp 30 remained virtually unaltered but decreased (-3,8, p<0,001) in the patients previously treated with HB.
Conclusion.
In routine clinical practice, patients with DM2 who failed to have target glycemia after treatment with basal insulin may benefit from transfer toDiAsp 30 without a rise in the frequency of hypoglycemia.