Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

NIRCa: An artificial neural network-based insulin resistance calculator.

BACKGROUND: Direct measurement of insulin sensitivity in children with type 1 diabetes is cumbersome and time consuming. OBJECTIVE: The aim of our study was to develop novel, accurate machine learning-based methods of insulin resistance estimation in children with type 1 diabetes. METHODS: A hyperinsulinemic hyperglycemic clamp study was performed to evaluate the glucose disposal rate (GDR) in a study group consisting of 315 patients aged 7.6 to 19.7 years. The group was randomly divided into a training and independent testing set for model performance assessment. GDR was estimated on the basis of simple clinical variables using 2 non-linear methods: artificial neural networks (ANN) and multivariate adaptive regression splines (MARSplines). The results were compared against the most frequently used predictive model, based on waist circumference, triglyceride (TG), and HbA1c levels. RESULTS: The reference model showed moderate performance ( R 2 = 0.26) with a median absolute percentage error of 49.1%, and with the worst fit observed in young (7-12 years) children ( R 2 = 0.17). Predictions of the MARSplines model were significantly more accurate than those of the reference model (median error 3.6%, R 2 = 0.44 P < .0001). The predictions of the ANN, however, showed significantly lower error than those of the reference model (P < .0001) and MARSplines (P < .0001) and better fit regardless of patient age. ANN-estimated GDRs were within a ±20% error range in 75% of cases with a median error of 0.6% and an R 2 = 0.66. The predictive tool is available at http://link.konsta.com.pl/gdr. CONCLUSIONS: The developed GDR estimation model reliant on ANN allows for an optimized prediction of GDR for research and clinical purposes.

Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D). MATERIALS AND METHODS: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation. RESULTS: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001). CONCLUSION: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

Obesity-Related Complications Including Dysglycemia Based on 1-h Post-Load Plasma Glucose in Children and Adolescents Screened before and after COVID-19 Pandemic.

Childhood obesity, with its metabolic complications, is a problem of public health. The International Diabetes Federation (IDF) has recommended glucose levels 1 h post oral glucose load (1h-PG) > 155-209 mg/dL as diagnostic for intermediate hyperglycemia (IH), while >209 mg/dL for type 2 diabetes (T2D). The aim of the study was to assess the occurrence of prediabetes, IH, and T2D in children and adolescents with simple obesity according to the criteria of American Diabetes Association (ADA) and of IDF, and the effect of COVID-19 pandemic on these disorders. Analysis included 263 children with simple obesity, screened either in prepandemic (PRE-113 cases) or post-pandemic period (POST-150 cases). All children underwent 2 h OGTT with measurements of glucose and insulin every 0.5 h, lipid profile, and other tests; indices if insulin resistance (IR): HOMA, QUICKI, Matsuda index, AUC (glu/ins) were calculated. The incidence of T2D, prediabetes, and IH was higher in POST with respect to PRE, with significant differences in the indices of IR, except for HOMA. Significant differences were observed in the assessed parameters of glucose metabolism among the groups with T2D, prediabetes, IH, and normal glucose tolerance (NGT), with some similarities between IH (based on 1h-PG) and prediabetes. Increased frequency of dysglycemia among children and adolescents with simple obesity is observed after COVID-19 pandemic. Metabolic profile of patients with IH at 1h-PG is "intermediate" between NGT and prediabetes.

Autoimmune reaction against pancreatic beta cells in children and adolescents with simple obesity.

Introduction: One of the most important complications of obesity is insulin resistance, which leads to carbohydrate metabolism disorders such as type 2 diabetes. However, obesity is also associated with development of an autoimmune response against various organs, including pancreatic beta cells. The prevalence of such autoimmune processes in children and their possible contribution to the increased incidence of type 1 diabetes is currently unclear. Therefore, the present study assessed the prevalence of autoantibodies against pancreatic islet beta cell's antigens in children and adolescents with simple obesity. Material and methods: This prospective observational study included pediatric patients (up to 18 years of age) with simple obesity hospitalized between 2011 and 2016 at the Department of Pediatrics, Diabetology, Endocrinology and Nephrology of the Medical University of Lodz. Children with acute or chronic conditions that might additionally affect insulin resistance or glucose metabolism were excluded. Collected clinical data included sex, age, sexual maturity ratings (Tanner`s scale), body height and weight, waist and hip circumference, amount of body fat and lean body mass. Each participant underwent a 2-hour oral glucose tolerance test with simultaneous measurements of glycaemia and insulinemia at 0`, 60` and 120`. In addition, glycated hemoglobin HbA1c, fasting and stimulated c-peptide, total cholesterol, as well as high- and low-density cholesterol and triglycerides were measured. Insulin resistance was assessed by calculating HOMA-IR index. The following autoantibodies against pancreatic islet beta cells were determined in each child: ICA - antibodies against cytoplasmic antigens of pancreatic islets, GAD - antibodies against glutamic acid decarboxylase, ZnT8 - antibodies against zinc transporter, IA2 - antibodies against tyrosine phosphatase, IAA - antibodies against insulin. Results: The study group included 161 children (57.4% boys, mean age 13.1 ± 2.9 years) with simple obesity (mean BMI z-score +2.2 ± 1.6). Among them, 28 (17.4%) were diagnosed with impaired glucose metabolism during OGTT [23 (82.2%) - isolated impaired glucose tolerance (IGT), 3 (10.7%) - isolated impaired fasting glucose (IFG), 2 (7.1%) - IFG and IGT]. Of the children tested, 28 (17.4%) were tested positive for at least one islet-specific autoantibody [with similar percentages in boys (15, 17.4%) and girls (13, 17.3%), p=0.9855], with ICA being the most common (positive in 18, 11.2%), followed by IAA (7, 4.3%), ZnT8 (5, 3.1%), GADA (3, 1.9%) and IA2 (1, 0.6%). There was no association between the presence of the tested antibodies and age, sex, stage of puberty, parameters assessing the degree of obesity, HbA1c, lipid levels and basal metabolic rate. However, autoantibody-positive subjects were more likely to present IFG or IGT in OGTT compared to those who tested completely negative (9, 32.1% vs 19, 14.3%, p=0.0280). Their HOMA-IR was also significantly higher (HOMA-IR: 4.3 ± 1.9 vs 3.4 ± 1.9, p=0.0203) and this difference remained statistically significant after adjusting for sex and age (p=0.0340). Conclusions: Children and adolescents with simple obesity presented a higher prevalence of markers of autoimmune response against pancreatic beta cells than the general population. Most often, they had only one type of antibody - ICA. The presence of autoimmune response indicators against pancreatic islet antigens is more common in obese patients with impaired carbohydrate metabolism and is associated with lower insulin sensitivity.

National Organ Transplant Registry in Poland. Poltransplant Activity.

BACKGROUND: In 2006 the National Transplants Registry administered by national transplant organization was introduced in Poland to monitor the results of organ transplantations. Statistical analysis is published yearly in the Poltransplant Bulletin, publicly available on the website and reported to European institutions. The transplant registry cooperates with other registers functioning online, based on the tool https://rejestrytx.gov.pl/. We present the formal analysis of data collected for the years 1996-2019. MATERIALS AND METHODS: Analysis covered the total number of organ transplantations in every transplant center; outcomes are related to recipients living with a functioning graft 1, 5, and 10 years after transplantation; results presented are real, not extrapolated. RESULTS: The total number of deceased-donor kidney transplantations was 20,606, the 1-year survival rate of recipients with a functioning graft was 90% (data completeness of 97%), and the 10-year survival rate was 59% (data completeness of 99%). The total number of deceased-donor liver transplantations was 4790; the 1-year survival rate of recipients with a functioning graft was 59% (data completeness of 98%). SUMMARY: The National Transplant Registry is an important tool for quality and safety systems in the transplantation field on the national level. The registry efficiently and effectively fulfills its tasks related to collecting records of all transplantations performed. Monitoring function for graft and recipient survival is also satisfied. The data provide an important and unique source of information to be used by transplant institutions and referred to in the literature.

The Current Status of Organ Donation and Transplantation in Poland. Poltransplant Activity.

BACKGROUND: This article summarizes comprehensive information about the current status of organ donation and transplantation in Poland. MATERIAL AND METHODS: Reported statistical data of solid organs and vascularized composite allograft donation and transplantation from both deceased and living donors in Poland in 2015-2020 (presented in tables according to selected variables) are based on the national transplant registries, gathering information on donation and transplantation activity in medical centers involved in donation and transplantation programs in Poland. RESULTS: In 2020 during the COVID-19 pandemic, 529 potential deceased donors were referred to the Polish Transplant Coordinating Centre Poltransplant; 1310 solid organs from 393 actual deceased donors (10.2 per million population) were procured, mostly kidneys (758), livers (285), and hearts (157). Eighty percent were multiorgan retrievals (314). In 2020, 1231 organs procured from deceased donors and 59 organs from living donors were transplanted to 1236 recipients. CONCLUSION: This overview indicates that donation and transplantation activity from deceased donors in Poland decreased about 20% in 2020 compared with 2019, which is comparable with worldwide rates. As the unprecedented pandemic situation affected donation and transplantation procedures, there are measures that must to be taken to return to prepandemic donation and transplantation rates in both deceased and living transplant programs and then continue to improve in the years to come.

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults.

INTRODUCTION: Confirmation of monogenic diabetes caused by glucokinase mutations (GCK-MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK-MODY is most prevalent. METHODS: The study evaluated the utility of lipid parameters in screening for patients with GCK-MODY. Eighty-nine children with type 1 diabetes and 68 with GCK-MODY were screened for triglyceride (TG), total and HDL cholesterol levels. Standardization against a control group of 171 healthy children was applied to eliminate the effect of development. Clinical applicability and cut-off value were evaluated in all available patients with GCK-MODY (n = 148), hepatocyte nuclear factor 1-alpha-MODY (HNF1A MODY) (n = 37) or type 1 diabetes (n = 221). RESULTS: Lower lipid parameter values were observed in GCK-MODY than in patients with type 1 diabetes. Standard deviation scores were -0·22 ± 2·24 vs 1·31 ± 2·17 for HDL cholesterol (P < 0·001), -0·16 ± 2·14 vs 0·60 ± 1·77 for total cholesterol (P = 0·03) and -0·57 ± 0·97 vs-0·22 ± 0·97 for TG (P = 0·05). Validation analysis confirmed that HDL cholesterol was the best parameter for GCK-MODY selection [sensitivity 87%, specificity 54%, negative predictive value (NPV) 86%, positive PV 56%]. A threshold HDL concentration of 1·56 mm offered significantly better diagnostic efficiency than total cholesterol (cut-off value 4·51 mm; NPV 80%; PPV 38%; P < 0·001). TG did not offer a meaningful cut-off value. CONCLUSIONS: HDL cholesterol levels measured in individuals with likely monogenic diabetes may be useful in screening for GCK-MODY and differentiation from T1DM and HNF1A-MODY, regardless of treatment or metabolic control.

Ultrafast acting insulin analog - a new way to prevent postprandial hyperglycemia and improve quality of life in type 1 diabetes patients - case reports.

The aim of modern insulin therapy used in the treatment of type 1 diabetes mellitus is to mimic the physiological secretion of insulin in order to ensure stable normoglycemia while maintaining the greatest possible comfort of life for diabetic patients. New ultra-fast insulin analogs that can be administered immediately before a meal contribute to the improvement of postprandial glycemia and the quality of life of patients. We presented two cases illustrating the effectiveness and safety of the use of an ultra-fast-acting insulin analog in the treatment of postprandial hyperglycemia in children with type 1 diabetes.

Nasal glucagon - a new way to treat severe hypoglycemia in patients with diabetes.

Hypoglycaemia is the most frequent acute complication of diabetes in patients treated with insulin. Severe hypoglycaemia can lead to life-threatening disorders. In addition, fear of hypoglycaemia remains a major obstacle to achieving therapeutic goals in diabetics, espe-cially with type 1. As such, both the prevention and treatment of hypoglycemia are so important in diabetes care. Treatment of hypoglycemia is still based on administration of glucose (oral or parenteral depending on the level of consciousness) or of glucagon injected intramuscularly or subcutaneously. In 1983, it was shown for the first time that intranasal glucagon drops increase blood glucose levels in healthy volunteers. In subsequent years, a new powder formulation of glucagon was developed, which is applied intranasally and passively absorbed through the nasal mucosa and it is not necessary to take a deep breath to take it. Intranasal glucagon is as effective as injectable glucagon and devoid of most of the technical problems associated with injectable glucagon. No serious adverse effects of the new preparation have been de-scribed so far. In December 2019 under the name Baqsimi TM (Eli Lilly, USA) has been approved by EMA for the treatment of severe hypoglycemia in patients since 4 years of age. Intranasal glucagon appears to be a breakthrough in the treatment of severe hypoglycemia in diabetic patients treated with insulin in both children and adults.

[Metabolic syndrome in young adults type 1 diabetic patients]. / Zespól metaboliczny u mlodych doroslych chorych na cukrzyce typu 1.

AIM: The aim of the study was to estimate the prevalence of metabolic syndrome (MS) in type 1 diabetic patients and to assess the relationship between the scores of MS components and body mass and metabolic control. MATERIAL AND METHODS: 165 patients aged 18-32 years with diabetes duration 8-26 years were included into the study. The height, weight, waist circumference and blood pressure were measured. HbA1c and plasma lipids concentrations were examined. Body mass index (BMI), waist/hip ratio (WHR) and daily dose of insulin were calculated. MS was diagnosed according to the definition of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) and International Diabetes Federation (IDF). RESULTS: The prevalence of individual components of MS was 10.3% for high triglycerides, 7.3% for low HDL, 27.9% for high blood pressure, and 10.3% for abnormal waist circumference according to NGEP and 18.8% according to IDF definition. After assuming that all type 1 diabetic patients fulfilled criteria for hyperglycemia, the prevalence of MS diagnosed according to NCEP was 10.9% (95% CI 6.1-15.7) and according to IDF was the same 10.9% (95% CI 6.1-15.7). In 14 patients MS was diagnosed according to both definitions, whereas 4 met only the NCEP, and another 4 met only the IDF criteria. Rrelationships between the scores of MS components and BMI (p < 0.0001) and HbA1c (p = 0.002) were found. Patients with MS were older than the patients without MS (p = 0.003) and needed higher insulin doses (p = 0.028). CONCLUSIONS: According to the NCEP and IDF criteria similar prevalence of MS is recognized in type 1 diabetic patients. Only in 2/3 of them MS is diagnosed according to both definitions. The most frequently occurring component of MS is elevated blood pressure. The scores of MS components are related to the presence of overweight and to poor metabolic control.

[Hypoglycaemia unawareness in patients with type 1 diabetes].

Hypoglycaemia unawareness, defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms, is an serious problem in type 1 diabetes mellitus. It is often caused by recurrent or severe hypoglycaemia, which leads to the failure of the autonomic nervous system (hypoglycaemia-associated autonomic failure - HAAF). The hypoglycaemia awareness can be restored by avoiding episodes of hypoglycaemia. Management of hypoglycaemia unawareness is complex, and can only be achieved by a multifactorial intervention of clinical care and structured patient education. In patients in whom functional intensive insulin therapy with insulin analogue, continuous subcutaneous insulin infusion using insulin pumps are ineffective in the prevention of hypoglycaemia the implementation of continuous glucose monitoring (CGM) is advisable. CGM systems equipped with low glucose alarms and prediction alarms not only significantly reduce the risk of severe hypoglycaemia, but also significantly reduce the fear of hypoglycaemia and improve the quality of life of patients and their families. The insulin pumps integrated with CGM automatically suspending insulin infusion when glucose is predicted to soon be low (PLGS) should be preferred in patient with hypoglycaemia unawareness. Hypoglycaemia management is complex and should also include structural education. Particular attention should be paid to the management of hypoglycaemia and appropriate use of modern therapy. The hypoglycaemia unawareness is very common among children under the age of 6 years who are unable to observe the early symptoms of hypoglycemia by themselves. This induces a high risk of frequent and severe hypoglycaemia, which can lead to structural changes in the brain, cognitive dysfunctions, poor mental abilities and behavioral disorders later in life.

Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes - a single center study.

Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011-2014) was performed in patients with T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA1c) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.

Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11.

BACKGROUND: A 12-week-old female presented with neonatal diabetes. Insulin therapy alleviated the diabetes, but the patient showed marked motor and mental developmental delay. The patient underwent genetic evaluation at the age of 6 years, prompted by reports that mutations in the KCNJ11 gene caused neonatal diabetes. INVESTIGATIONS: Genomic sequencing of the ATP-sensitive potassium (K(ATP)) channel gene KCNJ11 and in vitro functional analysis of the channel defect, and single-photon emission CT imaging before and after glibenclamide therapy. DIAGNOSIS: Genetic evaluation revealed a missense mutation (His46Leu) in KCNJ11, which encodes the Kir6.2 subunit of the K(ATP) channel, conferring reduced ATP sensitivity. Functional studies demonstrated that the mutant channels were strongly inhibited by the sulfonylurea tolbutamide. MANAGEMENT: Sulfonylurea (glibenclamide) treatment led to both improved glucose homeostasis and an increase in mental and motor function.

[Prehypertension in type 1 diabetic children and adolescents]. / Stan przednadcisnieniowy u dzieci i mlodziezy chorej na cukrzyce typu 1.

BACKGROUND: The elevated blood pressure is one of the most important risk factors of diabetic micro- and macroangiopathy. AIM OF THE STUDY: Evaluation of the prevalence of prehypertension and relationship between prehypertension, metabolic control and chronic complications in children and adolescents with type 1 diabetes mellitus. MATERIALS AND METHODS: 83 patients aged 12.0-18.9 years, with a duration of diabetes 0.5-17.3 years, without evidence of arterial hypertension were recruited. In all patients 24-hour automatic blood pressure monitoring was performed with oscillometric device. The individuals with >40% of systolic and/or diastolic blood pressure >120/80 mmHg were defined as prehypertensive. HbA(1)c was measured by HPLC, plasma lipid levels--by an enzymatic method and urinary albumin excretion rate by chemiluminescent enzyme immunoassay method. Body mass index (BMI) and daily dose of insulin were calculated. Ophthalmoscopic examination and power spectral analysis of heart rate variation were performed. RESULTS: In 30 individuals (36.1%) prehypertension was diagnosed. The prehypertension group had older age (17.5+/-1.1 vs. 15.9+/-2.3 years; p<0.001) and longer duration of the disease (7.3+/-4.7 vs. 4.7+/-3.4 years; p=0.005) as compared with the group with normal blood pressure. There were no significant differences between groups in HbA1c, daily dose of insulin, BMI-SDS, lipids profile, prevalence of microalbuminuria and retinopathy. In the patients with prehypertension the a greater activity of sympathetic activation was observed (LF/HF: 1.00+/-0.06 vs. 0.78+/-0.04, p=0.018). CONCLUSIONS: Prehypertension is frequently recognized in type 1 diabetic children and adolescents. The prevalence of prehypertension is associated with older age, longer duration of diabetes and the shift of the sympatho-vagal balance toward sympathetic activation. There is no relationship between prehypertension and metabolic control or the prevalence of microvascular complications.

[Insulin resistance in type 1 diabetic children and adolescents -- a simplified method of estimation]. / Wskaznik insulinoopornosci u dzieci i mlodziezy chorej na cukrzyce typu 1 -- uproszczony sposób oceny.

BACKGROUND AND AIM OF THE STUDY: Our own studies confirm the hypothesis, that insulin resistance of various degree is often observed in children and adolescents with type 1 diabetes mellitus (T1DM). The knowledge of this parameter characterizing individual patients may be of great value not only for better understanding of the disease course but also as a potential source of specific treatment. Reliable estimation of insulin resistance with hyperinsulinemic euglycemic clamp is a complex, laborious and costly procedure. These facts were enough to motivate us to make an attempt to elaborate an indirect, simplified method of insulin resistance assessment in T1DM children, that would be based on patients characteristics and on clinical parameters of the disease course. MATERIALS AND METHODS: 142 children and adolescents with T1DM (79 boys, 63 girls) aged 7.7-20.3 years (mean age - 13.7+/-3.3 years) were included into the study. Duration of diabetes was 0.5-12.5 years (mean 2.7+/-2.3 years). The stage of puberty was assessed by the Tanner scale. Euglycemic-hyperinsulinemic clamp by de Fronzo was performed to estimate insulin resistance. Glucose disposal rate (M index) determined during the last 30 min of the test estimated insulin resistance. Looking for clinical and metabolic factors characterizing insulin resistance: a) the plasma cholesterol, HDL-Ch, triglycerides and HbA1c were examined, b) the height, weight, waist circumference and blood pressure were measured, c) body mass index and daily dose of insulin were calculated. For statistical analysis the multiple regression was used (forward stepwise method). RESULTS: In the study group M index ranged from 2.1 to 17.4 mg/kg/min (mean 7.27+/-2.62 mg/kg/min). The boys presented better insulin sensitivity than girls (7.79 vs. 6.62, p=0.008). The insulin resistance depended on the patients' age (r=-0.46, p<0.001) and stage of puberty (p<0.001). A correlation between M index and insulin dose (r=-0.34, p<0.05) and HbA1c (r=-0.17; p=0.04) were found. There was a significant relationship between M index and parameters of adiposity, lipids and blood pressure. All significant clinical parameters of insulin resistance were subjected to the analysis. Multiple linear regression analysis was performed. The model with the strongest correlation with index M was used to work out the formula: M index = 17.065 + 1.547 x (gender: boys=1, girls=0) - 0,183 x (age) - 0,117 x (Waist circumference) - 2,019 x (Daily insulin dose) - 0,016 x (LDL-CH) + 0,041 x (DBP). CONCLUSION: In T1DM children and adolescents it is possible to estimate for daily use extent of insulin resistance on the basis of clinical features.

[Polymorphism I/D of the angiotensin-converting enzyme gene and disturbance of blood pressure in type 1 diabetic children and adolescents]. / Zaburzenia cisnienia tetniczego u dzieci i mlodziezy chorej na cukrzyce typu 1 a polimorfizm I/D genu enzymu konwertujacego angiotensyne.

AIM: The aim of the study was to evaluate an association between ACE genotypes and blood pressure (BP) disturbances in children and adolescents withType 1 diabetes mellitus. MATERIALS AND METHODS: 126 normo-albuminuric, type 1 diabetic children and adolescents at the age 10.5-19.7 years, and duration of diabetes 2.0-17.8 years, were included in the study. All patients were clinically normotensive and normoalbuminuric. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. The values of systolic BP, diastolic BP, mean arterial BP blood pressure and diurnal variation in BP were estimated. Prehypertension was diagnosed as BP values between 90pc or 120/80 mmHg and 95pc. ACE genotypes were assessed using polymerase chain reaction. RESULTS: In 48 individuals (38.1%) prehypertension was diagnosed. ACE genotypes distributed in patients were as follow: 31 (24.6%) genotype II, 45 (35.7%)--ID, and 50 (39.7%)--DD. Patients with DD genotype had higher nocturnal systolic BP (104 vs. 101 mmHg; p=0.029), diastolic BP (54 vs. 52 mmHg, p=0.003) and mean arterial BP (71 vs. 68 mmHg, p=0.003) as compared to carriers of the I allele (group ID + II). In the group DD in compare to the group ID + II lower nocturnal depletion in diastolic BP (18.0 vs. 20.5 mmHg, p=0.024) and mean BP (14.8 vs 16.6 mmHg, p=0.049) was observed. 14% patients of the DD group were non-dipper and 1.32% in the group ID + II (p=0.01). There was no differences in the prevalence of prehypertension between genotype groups (II+ID vs. DD: 38.2 vs. 38.0%, ns). CONCLUSIONS: Genotype DD is associated with nocturnal BP abnormalities in normotensive and normo-albuminuric children and adolescents with type 1 diabetes. There is no relationship between frequency of prehypertension and ACE gene polymorphism.

[Prehypertension risk factors in children and adolescents with type 1 diabetes]. / Czynniki ryzyka stanu przednadcisnieniowego u dzieci i mlodziezy chorej na cukrzyce typu 1.

AIM: Higher blood pressure is a marker of increased risk for development of diabetic angiopathy. The aim of the study was to evaluate the selected factors influencing the prevalence of prehypertension in T1DM children and adolescents. METHODOLOGY: 113 T1DM patients (62 male), aged 12-19 years, with diabetes duration from 0.5 to 17.3 years, without evidence of arterial hypertension during routine examination were recruited. In patients 24-hour automatic blood pressure (BP) monitoring was performed. Prehypertension was diagnosed SBP>120 mmHg and < 95pc and/or DBP>80 mmHg and < 95pc. Among metabolic factors body mass index (BMI), lipids profile, HbA1c and insulin sensitivity index glucose disposal rate (euglycemic hiperinsulinemic clamp) were estimated. As an early marker of autonomic neuropathy heart rate variation was measured. RESULTS: None of the study patients had hypertension. In 35 individuals (31%) prehypertension was diagnosed. The prehypertension group had older age (17.4 vs. 15.8 years, p<0.001), longer duration of disease (6.6 vs. 4.3 years, p=0.003), greater BMI (23.8 vs. 22.0 kg/m2, p=0.01) and lower insulin sensitivity index (5.9 vs. 7.0 mg/kg/min., p=0.04) as compared with the group with normal value of blood pressure. There were no differences between groups in lipids profile and HbA1c. In the patients with prehypertension the greater activity of sympathetic activation was observed (LF/HF--1. 0 vs. 0.82, p=0.02). CONCLUSIONS: Prehypertension is common feature in children and adolescents with type 1 diabetes. The prevalence of prehypertension is associated with older age, longer duration of disease, greater BMI, lower insulin sensitivity and the shift of the sympathovagal balance toward sympathetic activation.

Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes.

Gender and Age - Dependent effect of type 1 diabetes on obesity and altered body composition in young adults.

INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the influence of age and gender on the prevalence of overweight and obesity, body composition and fatty tissue distribution in young adults with type 1 diabetes. MATERIAL AND METHODS: 197 patients with type 1 diabetes aged 20-40 years participated in the study. The control group consisted of 138 healthy adults. Body weight, height, waist and hip circumferences were measured. Analysis of body mass composition was performed using the bioimpedance. Study groups were stratified into cohorts aged <30 and 30+ years. RESULTS: Overweight and obesity were diagnosed in 35.5% and 13.2% of diabetic patients and in 26.1% and 7.3% of the control group, respectively (p=0.016). In the whole study group, advanced age (OR=1.10; p<0.001) and diabetes mellitus (OR=2.25; p=0.001) predisposed patients to excess body weight. Women had a lower prevalence of overweight and obesity, but a trend toward excessive body mass was observed in diabetic females (OR=1.18; p=0.181). Diabetic females more often had abdominal obesity than control females (mean difference - 19.2%; p=0.020). Higher total body fat mass was found in the diabetic group (p=0.037). Diabetic females had a higher amount of absolute (p<0.001) and relative body fat mass (p=0.002), fat free mass (p=0.007), relative arm (p=0.007), leg (0<0.001) and trunk (p-=0.006) fat mass than control females. Diabetic males showed only higher relative fat mass of the lower limbs compared to control males (p=0.018). CONCLUSIONS: Patients with type 1 diabetes develop overweight and obesity in early adulthood more frequently than the general population and are characterized by higher body fat mass. Gender-related differences in body weight and composition in young type 1 diabetic adults were found.