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.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.

Monogenic diabetes prevalence among Polish children-Summary of 11 years-long nationwide genetic screening program.

BACKGROUND: Estimated monogenic diabetes (MD) prevalence increases as screening programs proceeds. OBJECTIVE: To estimate prevalence of MD among Polish children. SUBJECTS: Patients and their family members suspected of suffering from MD (defined as causative mutation in one of the Maturity Onset Diabetes of the Young or permanent neonatal diabetes mellitus genes) were recruited between January 2005 and December 2015. METHODS: Nationwide prevalence was estimated based on data from 6 administrative provinces (out of 16 in Poland) with high referral rates of patients (>10 per 100 000 children). RESULTS: During the analysis, probands from 322 of 788 screened families tested positive yielding a total of 409 children and 299 family members with MD. An average of 70 probands/year were referred. Screening success rate reached 40% over the study period. We estimated the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence estimates increased nearly 2-fold since our report in 2011 (4.4/100 000). However, the figure reached a plateau because of screening saturation in 2014 what was also proven by lowering of the median age of diagnosis lowered in time (R = -0.73, P = .0172) along with shortening of the delay between clinical and genetic diagnosis (R = -0.65, P = .0417). CONCLUSIONS: The screening for childhood MD in Poland reached a plateau phase after 10 years showing a stable prevalence estimate. The true frequency of MD in the overall population may be higher given later onset of reportedly more frequent types of MD than GCK -MODY.

Incidence of type 1 diabetes mellitus during 26 years of observation and prevalence of diabetic ketoacidosis in the later years.

UNLABELLED: The prevalence of type 1 diabetes (T1D) varies greatly between countries. However, over the past several decades, a global rise in the incidence of T1D in the pediatric population has been noted. The aim of our study was to investigate the incidence of T1D in children living in the Lesser Poland during the period of time from January 1, 1987, to December 31, 2012, and to analyze the demographic characteristics and occurrence of diabetic ketoacidosis (DKA) in patients with newly diagnosed T1D in the second part of the study (2006-2012). During 26 years, 636 children (331 boys, 305 girls) aged 0-14 years were newly diagnosed with T1D (0-4 years old, n = 131; 5-9 years old, n = 253, 10-14 years old, n = 252). The standardized incidence ratio (SIR) ranged significantly (p < 0.001) from 5.2/100,000/year in 1987 to 21.9/100,000/year in 2012. The highest SIR was observed in age group 5-9 years old (21.2) and the lowest in 0-4 years old (8.8). There was no association with sex or living in urban or rural area. On admission, DKA was diagnosed in 22.4 % of patients. There were no significant differences relating to the presence of DKA (p = 0.912) in subsequent years. CONCLUSIONS: The incidence of T1D among children is increasing rapidly with the highest SIR in the 5-9 years old age group. DKA is still an important problem in the pediatric population. WHAT IS KNOWN: • The incidence of pediatric type 1 diabetes mellitus in Europe is increasing. The initial manifestation of the type 1 diabetes mellitus is diabetic ketoacidosis. What is New: • This is the longest (26 years) continuous analysis of the incidence of type 1 diabetes in Poland and the first analysis focused on the incidence rate and also on presence of diabetic ketoacidosis.

The incidence and causes of acute hospitalizations and emergency room visits in adolescents with type 1 diabetes mellitus prior to and during the COVID-19 pandemic: a single-centre experience.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in childhood. Because acute glycaemic com-plications account for most concerns in the management of T1DM in children, special attention during the challenging time of the global COVID-19 pandemic is required to prevent deteriorations resulting in acute hospitalization. AIM OF THE STUDY: is to assess how the COVID-19 pandemic influenced the incidence and causes of acute hospitalizations and emergency room visits in adolescents with established type 1 diabetes mellitus, and to characterize the admitted population. MATERIAL AND METHODS: The study was conducted as a retrospective evaluation of acute hospitalizations of 39 T1DM patients between 15 and 17 years of age in the period 2018-2021. RESULTS: No difference was noted in the incidence of acute hospitalizations and DKA or the biochemical parameters of adolescents with T1DM between the pre-COVID (23 patients in 2018-2019) and COVID period (16 patients in 2020-2021). It is, howev-er, worth underlying that 6/11 (55%) patients hospitalised in 2021 experienced diabetes deterioration as a result of emo-tional distress - a phenomenon that was not present in the pre-COVID era. After excluding of the hospitalizations due to psy-chosocial causes, a significant decrease in the number of acute hospitalizations in the COVID period was observed. CONCLUSIONS: We suppose that increased parental supervision during the pandemic might have prevented some of the episodes of severe disease decompensation, but this was masked by the sharp increase in hospitalizations due to emotional distress. Our data confirmed that psycho-emotional status is an important factor in the treatment of T1DM.

Increased prevalence of celiac disease and its clinical picture among patients with diabetes mellitus type 1 - observations from a single pediatric center in Central Europe.

INTRODUCTION: The aim of our study was to analyze the incidence and the clinical characteristic of celiac disease (CD) in pediatric population with type 1 diabetes mellitus (T1DM). MATERIAL AND METHODS: The data of 880 patients with T1DM, 429 girls, mean age 12.14 ±4.0 years was retrospectively retrieved from medical records. Patients with T1DM and CD were selected and a detailed analysis of CD prevalence and its clinical characteristic at the time of CD diagnosis was performed. The data were compared with the previous data from our center published a decade ago. RESULTS: CD was suspected in 85/880 patients (9.65%) on the base of results of serological tests, but finally CD was diagnosed in 73/880 patients with T1DM (8.3%), in 53/429 girls (12.3%) and in 20/451 boys (4.4%). Most patients (71%) had CD diagnosed after T1DM onset. The majority of CD patients (72%) was asymptomatic. The CD diagnosis was not associated with inappropriate metabolic control of diabetes. The onset age of diabetes in children with CD was significantly lower than in those without CD (5.8 ±3.6 years vs. 7.56 ±4.0 years, p = 0.04). The prevalence of CD is significantly higher than a decade ago in our center (8.3% vs. 5.7%, p = 0.001). CONCLUSIONS: In light of increasing prevalence of mainly asymptomatic CD in patients with T1DM, CD screening is necessary. However positive serological tests, which are currently used in screening, and are the first step of diagnostics, in some patients allow only to suspect the CD and further diagnostic steps should be performed.

[Disorders of lipid metabolism in adolescents with simple obesity]. / Zaburzenia metabolizmu lipidów u mlodziezy z otyloscia prosta.

BACKGROUND: Obesity affects approximately 45 millions of children worldwide. Some of them present with secondary dyslipidemia that leads to premature atherosclerosis. AIM OF THE STUDY: 1) Assessment of the frequency and type of dyslipidemia in obese adolescents. 2) An attempt at defining risk factors of atherogenic lipid profile in obese adolescents. MATERIAL AND METHODS: In 146 (84 girls/62 boys) obese (mean BMI SDS 4.95, 95% CI 4.62-5.29) adolescents (age 10-18, mean 14.7 years), the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglicerydes (TG) were measured. Atherogenic dyslipidemia was defined as a high TG level with a concomitant low HDLc level. Standard oral glucose tolerance test was performed with the assessment of fasting and after 120' post-load of 75 g of glucose and insulin levels; the insulin resistance index HOMA-IR was calculated. RESULTS: The mean values of the lipid fractions were in normal ranges: TC 4.64 mmol/L (95% CI 4.48-4.8), LDLc 2.86 mmol/L (95% CI 2.73-2.99), TG 1.4 mmol/L (95% CI 1.3-1.5), and HDLc 1.16 (95% CI 1.1-1.2). However, in 50.69% of the patients (45.24% girls and 58.06% boys), elevated levels of TC, LDLc, and TG were observed respectively in 23.29%, 17.81% and 37.67%, and low HDLc in 15.07% of patients. A total of 10.96% of the patients presented with coexistence of a low HDLc and a high TG. In 26.7%, dyslipidemia was followed by arterial hypertension. There was a reverse correlation between a low HDLc value and BMI SDS [R (-) 0.22, p < 0.05] and not with TC, LDLc, and TG. The relative risk of abnormal lipid profile occurrence was higher in obese patients with insulin resistance (OR 1.72; 95% CI 0.8-3.4; p = 0.12), being significant only for boys (OR 3.67; 95% CI 1.1-12.1; p = 0.03). There was a reverse correlation between fasting insulin level, HOMA-IR and HDLc [R (-) 0.2; p < 0.05; R (-) 0.2; p < 0.05) respectively], as well as TG (R 0.26 ; p < 0.05; R 0.26; p < 0.05, respectively), and between post-load insulin level and TG (R 0.24; p < 0.05). CONCLUSIONS: 1) Lipid disorders occur in about one-half of obese adolescents, of which 10% presents with atherogenic lipid profile. 2) One of the most important risk factors of atherogenic lipid profile occurrence is insulin resistance, especially in boys. The severity of the obesity (BMI-SDS) is of lesser importance.

Increased Incidence of Type 1 Diabetes in Children and No Change in the Age of Diagnosis and BMI-SDS at the Onset - is the Accelerator Hypothesis not Working?

Objective: One of the hypothesized reasons for the observed increase in type 1 diabetes incidence in children is weight gain, causing accelerated disease development in predisposed individuals. This so-called accelerator hypothesis is, however, controversial. The aim was to analyze whether, in the ethnically homogeneous population of Lesser Poland, an increase in the number of cases of diabetes among children was associated with younger age and higher body mass index-standard deviation score (BMI-SDS) at the time of diagnosis. Methods: Retrospective data analysis from medical records of all patients <14 years (n=559; 50.6% male), with newly diagnosed type 1 diabetes, in Lesser Poland between 1st January 2006 and 31st December 2017 (11 years). Results: The incidence ratio ranged significantly (p<0.001) from the lowest in 2006 (11.2/100,000/year) to the highest in 2012 (21.9/100,000/year). The mean age of diagnosis was 8.2±3.5 years. There was no trend in decreasing diagnosis age (p=0.43). The mean BMI-SDS was -0.4±1.2. Almost all children (91.6%) presented with BMI-SDS within the normal range at the time of diagnosis, with only 2.7% of cases being obese and 5.7% underweight at the moment of diagnosis. There was no clear trend at all in BMI-SDS over the study period. Conclusion: These results do not corroborate an increase of type 1 incidence in paediatric population being associated with younger age of diagnosis and higher BMI-SDS. This implies that the accelerator hypothesis does not hold true in the study population.

[Obesity in children and adolescents and diabetes]. / Otylosc w wieku rozwojowym a cukrzyca.

The significant increase in the prevalence of obesity in children and adolescents over past decades caused the concomitant rise in the incidence of glucose intolerance and diabetes. Impaired glucose tolerance is present in 10-27% of obese children, while type 2 diabetes accounts for more than 10% of all cases of diabetes in Caucasian adolescents. Obesity may also accelerate the onset of type 1 diabetes. Insulin resistance with visceral and intramyocellular lipid accumulation, reduced adiponectin level and elevation of inflammatory cytokines play an important role in the pathogenesis of glucose metabolism disturbances. This article presented the influence of obesity on the development and clinical presentation of different types of diabetes and addresses the problems of differential diagnosis of diabetes type in obese children and adolescents. The recommendations for case finding and the treatment options taking into account the pathophysiology underlying hyperglycemia were discussed.

[Does the metabolic syndrome in children and youth exist?]. / Czy istnieje zespól metaboliczny u dzieci i mlodziezy.

There is an increasing incidence rate of overweight and obesity in last years. It concerns approximately 20% of children 7 to 11 years in our country, and even 30% in high developed countries. There is also simultaneous increase in frequency of the disturbances, that are dependent from obesity and insulin resistance, such as glucose and fats metabolism disorders, and arterial hypertension. They cause complications of cardiovascular system detected in the youngest children, such as thickening of the carotid wall and atherosclerotic lesions in the arteries. The metabolic syndrome (MS) may be recognized on the basis of appearance of these disorders in approximately 1-10% children in that group of age in general population, and in 10-67% in obese children. The differences depend on applied criteria (Cook, 2003; de Ferranti, 2004; Cruz, 2004; Weiss, 2004; Ford, 2005; IDF 2007), patients' age, and obesity duration, and may lead to non-recognition of MS in approximately 10-25% of obese children (using IDF 2007 criteria). The lack of recognition can lead to postponement of the treatment of each individual component of the syndrome, while every of them, and especially visceral obesity, is the independent risk factor of cardiovascular disorders, as well as preterm mortality. With passed regards, an attempt to establish or exclude the MS diagnosis is pointless, and even harmful, as well as searching for and specifying criteria of its recognition. The next arguments against MS recognizing are showed in adults: i) the weaker correlation between the MS recognized in patients using recently recommended IDF 2005 criteria and later cardiovascular complications, in contrary to earlier criteria (ATP III) ii) no proof for higher risk of complications development in cases with three components of the MS, in comparison to cases with only two criteria (ATP III), and iii) the lack of influence of MS diagnosis on the way of treatment of each component. It is necessary to start the treatment in case of revealing of any risk factor, as well as to look for other disorders. They can be recognized on the basis of specific for sex and age MS diagnostic criteria. However it has to be considered, that in IDF 2007 criteria the value of upper limit of normal arterial pressure in children (> or =130/85 mmHg) has been settled arbitrarily, without taking into account the age nor the sex, and the waist circumference, as the indicator of visceral obesity, does not correlate in children, contrary to subcutaneous fat tissue content, with the degree of insulin resistance. The basis of the therapy of metabolic disorders in MS, is the treatment of obesity, and especially its prophylaxis. The settlement of the pharmacological treatment modality and the age of its beginning needs further investigations.

Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects.

Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive K(+) channel (K(ATP) channel), are a common cause of neonatal diabetes. We identified a novel KCNJ11 mutation, R50Q, that causes permanent neonatal diabetes (PNDM) without neurological problems. We investigated the functional effects this mutation and another at the same residue (R50P) that led to PNDM in association with developmental delay. Wild-type or mutant Kir6.2/SUR1 channels were examined by heterologous expression in Xenopus oocytes. Both mutations increased resting whole-cell currents through homomeric and heterozygous K(ATP) channels by reducing channel inhibition by ATP, an effect that was larger in the presence of Mg(2+). However the magnitude of the reduction in ATP sensitivity (and the increase in the whole-cell current) was substantially larger for the R50P mutation. This is consistent with the more severe phenotype. Single-R50P channel kinetics (in the absence of ATP) did not differ from wild type, indicating that the mutation primarily affects ATP binding and/or transduction. This supports the idea that R50 lies in the ATP-binding site of Kir6.2. The sulfonylurea tolbutamide blocked heterozygous R50Q (89%) and R50P (84%) channels only slightly less than wild-type channels (98%), suggesting that sulfonylurea therapy may be of benefit for patients with either mutation.

[The usage of the personal insulin pump for treatment of a 7 week infant with neonatal diabetes mellitus]. / Zastosowanie osobistej pompy insulinowej u 7-tygodniowego niemowlecia z cukrzyca noworodkowa.

UNLABELLED: Etiology and the course of diabetes mellitus type 1 diagnosed in infancy remains the subject of intensive investigations, nonetheless the diagnosis of hyperglycemia in this period obliges prompt start of the insulin therapy. The treatment of newborns and infants is challenging because of the necessity to use very low doses of insulin. CASE REPORT: A boy was transferred from the neonatal ward on the 8th day of life with the diagnosis of diabetes mellitus. He was born of young healthy parents (mother: 27, father: 30 years old), with no family history of diabetes or other autoimmune disorders. The course of the pregnancy remained normal until 37th week of gestation when due to alterations in the fetal heart rate the cesarean section was done. In spite of precise i.v. insulin therapy fluctuations in glucose levels persisted. Additionally the achievement of the metabolic compliance was complicated by generalized infections caused by hospital pathogens that required broad-spectrum i. v. antibiotic therapy. At the age of 7 weeks personal insulin pump Pradigm 712 for the delivery of NovoRapid insulin was introduced. Already on the 3rd day of such treatment, the daily insulin dose could be decreased from 0.7 unit/kg/24 hrs down to 0.5 unit/kg/24 hrs, and glucose levels normalized. In the course of this treatment the patient weighed 6300 g at the age of 6 months, and his psychomotoric development reached the milestones adequate for the age. The biochemical examinations revealed C-peptide levels both fasting and after glucagon stimulation <0.5 ng/ml. Additionally, the analyzed immunologic markers of type 1 diabetes are negative. The genetic testing for Kir6.2 mutation gave negative results. CONCLUSIONS: The presented case shows that the insulin therapy carried out via personal insulin pump is the possible and effective treatment in children diagnosed with diabetes mellitus during infancy.

Noninsulinoma pancreatogenous hypoglycaemia in adults--a spotlight on its genetics.

Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as "nesidioblastosis". Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic ß-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations.

[Thyroid peroxidase antibodies and thyroid diseases in children and adolescents with newly diagnosed type I diabetes]. / Wystepowanie przeciwcial przeciw peroksydazie tarczycowej i chorób tarczycy u dzieci i mlodziezy ze swiezo rozpoznana cukrzyca typu 1.

The objective of the authors was to evaluate the prevalence of TPO Ab and thyroid diseases in children with newly diagnosed type 1 diabetes. The examination included 153 patients (85/55.6% girls) from southeast Poland aged 11 months to do 17.4 years (mean age 9.5 +/- 3.9 years). Apart from clinical assessment, all children had determinations made of serum TPO Ab, FT4 and TSH, while thyroid ultra sound was performed in each patients with abnormal thyroid morphology and/or positive TPO Ab titter. Positive TPO Ab was detected in 45 patients (29.4%). In this group 26 had isolated serum TPO Ab elevation, 18 had Hashimoto's disease, 1 Graves's disease. Another 12 children (7.8%) were demonstrated to have euthyroid goiter. Thyroid abnormalities were thus seen in 37.2% children with newly diagnosed type 1 diabetes. No association was demonstrated between the prevalence of thyroid abnormalities and sex. Children with subclinical stage of autoimmune thyreoiditis were significantly younger in comparison to patients with Hashimoto's disease (8.9 +/- 4.2 vs. 12.0 +/- 3.1 years) and had significantly lower serum TPO Ab and TSH levels (314.2 +/- 232.4 vs. 2076.8 +/- 1300.8 U/ml, 1.7 +/- 0.82 vs. 4.1 +/- 2.9 ulU/ml, respectively). Thyroid dysfunction was detected in 7 (4.6%) children with newly diagnosed type 1 diabetes. In comparison to the entire group with positive serum TPO Ab titer in these 7 children the percentage of patients with thyroid dysfunction was significantly higher (15.5%). Six patients were hypothyroid and 1 had hyperthyreosis. The present results justify the need for comprehensive screening for thyroid disorders in all children with newly diagnosed type 1 diabetes.

[Thyroid peroxidase antibodies and thyroid diseases in children and adolescents with type 1 diabetes mellitus from Southeast Poland]. / Przeciwciala przeciw peroksydazie tarczycowej i choroby tarczycy u dzieci i mlodziezy z cukrzyca typu 1 z Polski poludniowo-wschodniej.

The authors evaluated the prevalence of TPO Ab and thyroid disorders in 219 children and adolescents (119/54% girls) with type 1 diabetes from southeast Poland aged 3.2-22.3 years (mean age-13.7 +/- 3.9 years). Their age upon diagnosis ranged from 1.6 to 17.2 years (mean age--8.1 +/- 3.6 years), while diabetes duration was between 1 and 18.7 years (mean, 6.4 +/- 3.7 years). In addition to clinical assessment of all patients, determinations were made of serum TPO Ab, FT4 and TSH; thyroid ultrasound was performed in each patient with abnormal thyroid morphology and/or positive TPO Ab titer. Positive TPO Ab titer was demonstrated in 76 (34.7%) patients with type 1 diabetes; in this group 49 showed no other overt thyroid pathological symptoms. Hashimoto's disease was detected in 26 children, Graves's disease in 1 girl. Twenty children (9.1%) with negative TPO Ab titter were shown to have euthyrotic goiter. Thus, thyroid abnormalities were demonstrated in 43.8% of the patients and were seen twice as often in girls than in boys (+ n = 69 > n = 27). Thyroid dysfunction was detected in 11 (5.05%) patients. These 11 patients with thyroid dysfunction constituted 14.5% of the entire group of children with both type 1 diabetes and positive TPO Ab titer (n = 76). Ten patients were hypothyroid (including 8 with previously undiagnosed disease) and 1 girls had hyperthyroidism. The present results indicate that in each child with type 1 diabetes--apart from diabetes control--thyreologic assessment should be done, and the frequency and type of examinations should depend on the comprehensive preliminary evaluation.

Metabolic control and its variability are major risk factors for microalbuminuria in children with type 1 diabetes.

INTRODUCTION: To assess in a prospective study the course and the predictors of microalbuminuria in children and adolescents with type 1 diabetes. MATERIAL AND METHODS: 438 children and adolescents who developed diabetes in the years 1985-2004 were followed for 9.2 ± 3.4 years from the diagnosis. Microalbuminuria was assessed on the basis of timed overnight urine collections performed once per year. Variability of glycated haemoglobin was expressed as a coefficient of variation (%) calculated by dividing standard deviation (adjusted for the number of measurements) by mean of HbA1c. RESULTS: Microalbuminuria was noted in 99 patients (22.6%) after 8.27 ± 3.3 years of diabetes. In 29 individuals (6.6%), microalbuminuria was persistent. The prevalence of microalbuminuria was not dependent on the period of diabetes diagnosis. During followup, 17 (58.6%) patients with persistent MA reverted to normoalbuminuria. Children without any episodes of microalbuminuria had significantly lower HbA1c variability (8.44%; 95% CI 7.81-9.08%) than those with one (10.28% 95% CI 9.10-11.47%; p = 0.007). The difference of HbA1c variability between patients with and without microalbuminuria persisted after correction by mean HbA1c (p = 0.04). Risk factors for ever developing microalbuminuria during the observation period in multivariate analysis included: mean HbA1c (HR [95% CI]: 1.17 [1.00-1.37; p = 0.05]) and its variability (1.04 [1.00-1.07]; p = 0.05), insulin dose (HR per 0.1 unit*kg- 1*day-1: 0.87 [0.79-0.96]; p = 0.005), presence of arterial hypertension (1.63 [1.07-2.49]; p = 0.02), and age at onset of diabetes (1.15 [1.08-1.21]; p < 0.0001). CONCLUSIONS: Children who develop microalbuminuria are characterised by poorer and more variable metabolic control, hinting at the importance of interventions aimed at both improvement and stabilisation of HbA1c levels.

[Quality of treatment in children with type 1 diabetes based on the Polish Prospective Pump Programme]. / Jakosc leczenia dzieci z cukrzyca typu 1 w oparciu o ogolnopolski prospektywny program leczenia przy uzyciu pomp insulinowych.

BACKGROUND: In pediatric patients with type 1 diabetes mellitus, the value of HbA1c is a predictor of the risk of late systemic complications in adulthood. In the last years significant changes in the method of treatment in pre-pubertal children with T1DM have taken place. However, there is lack of precise data concerning the results of metabolic control of this group of patients. THE AIM: was to assess the impact of the Polish Prospective Insulin Pump Programme (OPPLP) on the quality of metabolic control in prepubertal children with T1DM. The OPPLP included also education for diabetological staff (HPC) from the Polish Diabetic Centres as well as standardization of continuous subcutaneous insulin infusion (CSII) implementation procedures. MATERIAL AND METHODS: Population studies were conducted in the years: 2005-2008. 920 patients were enrolled at age from 1.2 to 14.6 years (median 8.5 years). 71.75 % of patients were in pre-pubertal age. 734 patients received CSII therapy. The cross sectional, prospective study, conducted according to the protocol of the OPPLP with clinical data collection from 2005 to 2008. We analyzed the data obtained during 1657 visits and assessed 1657 blood samples for HbA1c value in the Central Laboratory. The clinical data were recorded in the electronic net-database. RESULTS: In whole group the median of HbA1c was 7.46 % (min. 5% - max. 12.1%); 60.1% patients has HbA1c below 7.5%. The quality of treatment was comparable among the centres: med. HbA1c ranged from min. 6.5% to max. 8.0%. During the period from 2005 to 2008 effective results were obtained in glycemic control: med. HbA1c: 2005 - 7.6%, 2006 - 7.2%, 2007 - 7.0% and 2008 - 7.5%. Slightly higher HbA1c was observed in children with longer duration of diabetes (r=0.17, p<0.005). CONCLUSIONS: The OPPLP, including HCP education, enabled optimalization of metabolic control in the prepubertal children switched pump therapy. Moreover, the programme brought about an even level of treatment between the Polish Diabetic Centres irrespective of their size. It is important to continue the programme and to develop a country level register of children with T1DM.

Equal metabolic control but superior caregiver treatment satisfaction with insulin aspart in preschool children.

BACKGROUND: The aim of this study was to compare the metabolic outcomes, safety, and caregiver treatment satisfaction of basal-bolus multiple daily injection (MDI) therapy with mealtime insulin aspart (IAsp) or human insulin (HI) (both with basal NPH insulin), or of continuous subcutaneous infusion (CSII) with IAsp in preschool-age children with type 1 diabetes mellitus. METHODS: After a 3-week HI MDI run-in, 61 children <7 years old were randomized to IAsp MDI or HI MDI or allocated to IAsp CSII for 26 weeks. Efficacy measures were glycated hemoglobin (A1C) and overall metabolic control at study end point. Safety evaluation included hypoglycemia and adverse events. Caregiver treatment satisfaction was evaluated using a World Health Organization questionnaire with 7-point scale answers. RESULTS: A1C level and overall metabolic control remained unchanged in all groups. Minor hypoglycemic episodes were equivalent between groups; few major hypoglycemic events occurred. Caregivers of children receiving IAsp CSII documented a greater increase in treatment satisfaction total scores (P = 0.04 vs. HI MDI and IAsp MDI group) and expressed satisfaction with the frequency of hypoglycemic events. CONCLUSIONS: After 26 weeks of treatment with IAsp CSII, IAsp MDI, or HI MDI, all metabolic control parameters remained unchanged and equivalent. Caregiver treatment satisfaction was higher in parents who chose IAsp CSII pump therapy for their children.

Efficacy and safety of sulfonylurea use in permanent neonatal diabetes due to KCNJ11 gene mutations: 34-month median follow-up.

BACKGROUND: Recently, many patients with Kir6.2-related permanent neonatal diabetes mellitus (PNDM) have been successfully transferred from insulin therapy to sulfonylurea (SU) treatment. The long-term efficacy and safety of SU treatment in PNDM patients, however, have not yet been determined. METHODS: We monitored glycemic control and the occurrence of potential side effects in 14 Kir6.2-related PNDM patients from Poland (median age, 12.0 years; range, 5-50 years) who were transferred to SU therapy at least 2 years ago. Three of the 14 patients were lost to follow-up, whereas for the remaining 11 individuals the median follow-up was 34 months (range, 27-51 months). RESULTS: The initial reduction of glycated hemoglobin (HbA1c) after the switch to SU (approximately 3-6 months post-transfer) was 1.68% (range, 0.3-3.7%), and good metabolic control was maintained over the entire period of observation with an average HbA1c level of 6.0% (range, 5.3-6.7%) at the last visit. This was accompanied by a substantial drop in SU dose by 0.24 mg/kg, which constituted a 38.0% decrease. A rapid progression of retinal changes was observed in one patient, a 34-year-old woman at the beginning of the observation, with preexisting proliferative diabetic retinopathy. No causal relationship between these changes and SU treatment could be proven. Neither serious side effects nor progression of diabetes complications was observed in any other patients. No detrimental effect on growth in the observed minors was recorded. CONCLUSIONS: In summary, the switch from insulin therapy to SU treatment in PNDM related to KCNJ11 mutations was found to be an efficient and safe therapeutic method over a period of 34-month median follow-up. Although no serious side effects were associated with SU treatment, their use in Kir6.2 PNDM requires further attention, particularly in children, adolescents, and patients with advanced chronic diabetes complications.