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.

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.

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.

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.

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.

[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.

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.

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.

The Pro12Ala PPARg2 gene polymorphism involves residual C-peptide secretionand BMI in type 1 diabetes.

INTRODUCTION AND AIM: Since insulin resistance is genetically determined and observed in type 1 diabetes, the study was designed to elucidate an involvement of Ala 12 Pro PPARg2 gene polymorphism in residual C-peptide secretion and BMI variation in children with type 1 diabetes. MATERIAL AND METHODS: In 103 patients with type 1 diabetes genetic analysis of PPARg2 polymorphism, C-peptide measurements and evaluation of BMI and clinical parameters were performed. Control group consisted of 109 healthy subjects. RESULTS: In diabetic patients, only three individuals exhibited Ala 12 Ala genotype (2.9%) and 29 patients were heterozygous Ala 12 Pro (28.2%). Interestingly, Ala12+ variants were associated with higher C-peptide levels in 6 th , 12 th and 24 th months after the onset than Pro 12 Pro genotype (0.39±0.24 pmol/mL vs. 0.22±0.14 pmol/mL, P=0.007 and 0.19±0.09 vs. 0.11±0.07, P=0.01 and 0.13±0.09 vs. 0.07±0.05, P=0.021, respectively). Similarly, C-peptide was also significantly increased in patients with history of type 2 diabetes in the first-degree relatives. The observation was even more evident when Ala12+ variants were taken together with family history of type 2 diabetes. Besides, in 24 th and 36 th months after the onset, Ala12+ variants revealed to be associated with higher BMI normalized by age and sex as compared to Pro 12 Pro (0.557±0.84 vs. -0.119±0.73, P=0.001 and 0.589±0.919 vs. 0.066±0.630, P=0.016, respectively). CONCLUSIONS: Thus, it is likely that PPARg2 gene polymorphism and/or the genetically determined insulin resistance may be associated with residual C-peptide secretion and involve excessive BMI in type 1 diabetes.

The impact of having siblings - analysis of "hygiene theory" of chronic diseases in patients with type 1 diabetes in population of the Lódz region Hygiene theory and type 1 diabetes.

INTRODUCTION: In the recent years there has been a significant increase in the incidence of the type 1 diabetes mellitus. Therefore, numerous studies are underway to evaluate the possible factors underlying this trend. Some studies suggest that better sanitary conditions and lack of contact with microorganisms might be important, thus increasing the risk of disease in firstborns. Moreover, siblings could play an important role in the transmission of pathogens, which, by stimulating the immune system, may prevent the development of atopic and autoimmune diseases including such as type 1 diabetes. Current data, however, are still inconclusive. PURPOSE: The aim of the study was to evaluate the effect of having siblings on the incidence of type 1 diabetes among children and adults. MATERIALS AND METHODS: A group of 469 patients with type 1 diabetes was selected. The study population was composed of 245 adults and 224 youth patients. Information from Outpatient Diabetologic Departments database was gathered. Data such as age at the diagnosis of diabetes, sex of siblings, number and birth order were analyzed. RESULTS: In the studied population, 4.5% were only children, and 30.3% patients came from large families. In the group of type 1 diabetic patients 39.7% were firstborns and this proportion was comparable to the group of healthy subject. The highest proportion of firstborns was noted in the group that was diagnosed after 18 years of age (45,1%) compared to the group that was diagnosed between 10 and 14 (29,1%) (p<0.05). Type 1 diabetic patients that were not firstborns much more often had older siblings of the opposite sex than the same sex. CONCLUSIONS: he firstborns in the population of type 1 diabetes from the Lódz region did not outnumber the healthy subjects. Significantly higher proportion of firstborns in the group that was diagnosed after 18 years of age compared to the group that was diagnosed between 10 an 14 years was noted.

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.

Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion.

OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.

[Epidemiology and clinical course of diabetic ketoacidosis in children and adolescents with type 1 diabetes mellitus]. / Epidemiologia i obraz kliniczny cukrzycowej kwasicy ketonowej u dzieci i mlodziezy chorujacej na cukrzyce typu 1.

INTRODUCTION: Despite the progress in diagnosis and treatment of type 1 diabetes, diabetic ketoacidosis (DKA) is still a serious clinical problem. The aim of the study was too describe the epidemiology and clinical characteristic of DKA in children and adolescents with type 1 diabetes. MATERIAL AND METHODS: Medical records of 650 patients with type 1 diabetes who were under care of the Outpatient Clinic for Diabetic Children of the Medical University of Lodz from 1st January 2007 till 31 December 2009 were analysed. RESULTS: 101 cases of DKA were reported; the incidence of DKA was 5.2/100 patients /year. Episodes of DKA occurred in 89 patients (39 girls and 50 boys). In 82 patients 1 episode of DKA was recorded, in 3 patients - 2 episodes, in 3 patients - 3 episodes and in 1 patient - 4 episodes. 58.4% (59/101) of DKA episodes occurred in patients with newly diagnosed diabetes (mean age: 8.04-4.78 years) and 41.6% (42/101) - in children with established type 1 diabetes (mean age: 13.3-3.37). DKA was diagnosed in 26,1% of children with new onset of the disease. The most frequent causes of DKA in patients with established type 1 diabetes were noncompliance (22/42) and acute infectious diseases (12/42). Severe DKA was diagnosed in 19/101 episodes, moderate - in 36/101 and mild - in 46/101. No lethal complication of DKA was recorded. The following complications of DKA were observed: dyselectrolitemia (68/101), acute pancreatitis (5/101), gastrorrhagia (1/101), insulin oedema (1/101). Mean duration of hospitalization was 12.03-5.58 days. CONCLUSIONS: Newly diagnosed type 1 diabetes is the main cause of DKA in children and adolescents.In established type 1 diabetes the most frequent cause of DKA is poor quality of self-management. Dyselectrolitemia is the most frequent complication of DKA in children. Acute pancreatitis should be considered in a young patient with DKA.

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.

Free fatty acids level may effect a residual insulin secretion in type 1 diabetes.

INTRODUCTION: Recent studies on the pathogenesis of type 1 diabetes (T1DM) show that autoimmune activity in human pancreatic 1-cells is accompanied by abnormalities of fatty tissue metabolism, which is the underlying process in type 2 diabetes.The aim of the study was to determine the correlation between C-peptide concentration, indicating residual insulin secretion, and free fatty acids (FFA) level in children with T1DM. MATERIAL AND METHODS: We recruited 178 diabetic patients (mean age 10.8 years; M/F 99/79). In all individuals the fasting C-peptide by a radioimmunological method and FFA serum levels using an enzymatic colorimetric method were measured at the onset and after 6 months of the diabetes duration. RESULTS: Thirty four (19.1%) of the patients had the C-peptide level above the lower limit of normal range (>0.28 pmol/ml) at both time points. FFA level at onset was significantly higher as compared to the level after 6 months of follow-up (38.4+29.4 vs. 28.9 ± 23.1 mg/dl; p=0.0003). However, both values were positively correlated (r=0.31; p=0.0008). Interestingly, a negative correlation was found between FFA and C-peptide measurements at onset (r=-0.19; p=0.01) and at 6th month of the disease (r=-0.18; p=0.02). Moreover, when the C-peptide level was treated as a binominal variable(above and below 0.28 pmol/ml) higher levels of FFA were observed in children with C-peptide deficiency at onset of diabetes (41.1 vs. 29.9 mg/dl; p=0.03) and a similar trend was noticed at 6th month of the disease (31.0 vs. 23.7 mg/dl; p=0.1). No relation of FFA with age at onset, gender,insulin requirement and HbA1c were revealed. CONCLUSIONS: The obtained results, which link the FFA level with residual insulin secretion in T1DM,may serve as further evidence supporting the contribution of fatty tissue metabolism in the patho-genesis of T1DM.

[One-year variability of HbA1c in children and adolescents with type 1 diabetes - preliminary results]. / Zmiennosc stezen HbA1c w populacji dzieci i mlodziezy chorych na cukrzyce typu 1 - doniesienie wstepne.

INTRODUCTION: The glycated A1c hemoglobin (HbA(1)c) is an accepted marker of glycemic control in patients with type 1 diabetes (T1DM) and a predictor of long-term microvascular diabetic complications. There have been reports of seasonal fluctuations of HbA(1)c levels in type 1 and type 2 diabetic patients of different age. AIM OF THE STUDY: The aim of the study was to investigate retrospectively investigate seasonal variations of HbA(1)c levels in a pediatric population of T1DM patients over a one-year period. MATERIALS AND METHODS: The study group included 473 patients aged 2.4 -18 years (mean 13.3 ± 3.7) with T1DM duration of at least 6 months in whom HbA(1) c levels were tested between November 1, 2008 and October 31, 2009. HbA(1)c was measured by high performance liquid chromatography (HPLC). RESULTS: The total number of 1417 HbA(1)c tests were performed (mean 3.0 tests/patient/year). Mean HbA(1)c level was (mean ± SD) 7.7 ± 1.5% (range 5.2 -15.7%; median 7.4%; 25-75% range: 6.7 -8.2%). Statistically significant differences in monthly HbA(1)c levels were found (analysis of variance; p < 0.001). The lowest HbA(1)c levels, observed in August and September, were significantly lower than in February, March, April and December. Relative HbA(1)c levels, expressed as percentages of individual patient's mean value for twelve months, showed similar seasonal fluctuations: the lowest values were observed in August and September and the highest were noted in February, March, April, November and December. CONCLUSIONS: 1. HbA(1)c levels in young T1DM patients show seasonal variability. 2. Considering seasonal HbA(1)c fluctuations in patients education and management schedules could improve glycemic control. 3. Seasonal changes of HbA(1)c levels should be considered in short-term(lasting several months) clinical study designs.

Neonatal diabetes in a child positive for islet cell antibodies at onset and Kir6.2 activating mutation.

In contrast to the autoimmune type 1 diabetes, patients with monogenic diabetes due to KCNJ11 mutations do not have pancreatic auto-antibodies at onset. Here we describe a patient diagnosed at the age of 12 weeks that showed ICA at diagnosis, yet has been tested with positive result for KCNJ11 mutation.