"The obesity pandemic" in the COVID-19 pandemic - new treatment for an old problem.

Obesity is a worldwide problem, and the fact that it increasingly affects children and adolescents is worrying. The COVID-19 pandemic and the restrictions introduced affected the physical activity of children and adolescents, and changed their lifestyle and the amount of time spent in front of screens, which are significant factors correlated with weight gain. Due to the scale of the problem of obesity and overweight, much attention is currently paid to seeking effective forms of therapy in these different, difficult circumstances. Interventions promoting a healthy lifestyle among obese children after the COVID-19 pandemic are particularly important and necessary. This article provides a review of the literature on the recent worsening of obesity in the paediatric population, with particular emphasis on the importance of the COVID-19 pandemic. New methods of fighting obesity with the use of telemedicine and current methods of pharmacotherapy, including new drugs, are presented.

Psychiatric Comorbidities in Pediatric Monogenic Diabetes due to GCK Mutation: Impact on Diabetes-Related Quality of Life.

BACKGROUND: Monogenic diabetes caused by mutation in the glucokinase gene (GCK-MD) is a rare disorder manifesting in childhood as mild, prevalent hyperglycemia. By consensus, it is managed by dietary supervision and infrequent consultations. However, its impact on the mental health of the affected children is largely unknown. OBJECTIVE: To estimate the prevalence of psychiatric comorbidities in children with monogenic glucokinase-related diabetes (GCK-MD) and evaluate their association with quality of life (QoL). METHODS: The study invited children with GCK-MD aged 5-18 years identified in the Central National Registry and treated in 3 pediatric diabetes centers in Poland. The control group comprised children with type 1 diabetes (T1D, the most common diabetes type in youth) matched for age and family history of diabetes. Participants underwent a semistructured clinical interview diagnostic for psychiatric comorbidities, questionnaires assessing behavioral problems, depressive symptoms, parental stress, and measuring general and diabetes-related QoL (PedsQl). RESULTS: We included 35 patients with GCK-MDMD and 199 with T1D. Eight (22.9%) GCK-MD patients were diagnosed with psychiatric disorder in their lifetime, compared with 16 (8.1%) in the T1D group (odds ratio 3.4 [95% confidence interval: 1.3-8.7]). Patients with GCK-MD showed better parent-reported general QoL (87.1 ± 11.9 vs 82.0 ± 14.0, P = 0.0060) and higher diabetes-related QoL in both parental (84.5 ± 13.8 vs 74.1 ± 15.2, P < 0.0001) and child's perspective (87.6 ± 10.9 vs 77.3 ± 13.9, P < 0.0001). Psychiatric disorders (+P) were associated with worse child-reported diabetes QoL (T1D+P 66.6 ± 16.7, T1D-P 78.2 ± 13.3, GCK-MD+P 79.6 ± 16.3, GCK-MD-P 90.1 ± 7.5, P = 0.0002). CONCLUSIONS: High prevalence of psychiatric disorders in children with GCK-MD and lower QoL emphasizes the need for psychologic surveillance in those otherwise mildly-treated patients.

The usefulness of the nutrition apps in self-control of diabetes mellitus - the review of literature and own experience.

Intensive technology development as well as the COVID-19 pandemic has contributed to the increased interest in the telemedicine and mHealth sector. Increasing availability and use of mobile devices as well as the constantly growing number of nutritional mobile applications, resulted in creating new tools for food and meals nutrients calculation which can be used by patients with diabetes. Variety of mobile applications and multiple functions included in them enable finding applications focused on individual patients' needs. The scientific data coming from research conducted so far suggest that the regular use of mobile nutritional applications contributes to improving metabolic control of diabetes and the reduction of the value of glycated hemoglobin in patients with diabetes. Innovative solutions bring hope also for a significant improvement in the quality of life of patients. The aim of this article was to summarize the EBM knowledge about the use of mHealth in self-control and diet of patients with diabetes, especially type 1 and to present and assess the nutrition mobile applications available in polish language according to their functionality in diabetic self-control.

The Association between Treatment Modality, Lipid Profile, Metabolic Control in Children with Type 1 Diabetes and Celiac Disease-Data from the International Sweet Registry.

BACKGROUND AND AIMS: A higher frequency of dyslipidemia is reported in children with type 1 diabetes (T1D) and celiac disease (CD). Recently, continuous subcutaneous insulin infusion (CSII) has been associated with better lipid profiles in patients with T1D. The aim of this study was to investigate the association between treatment modality and lipid profile, metabolic control, and body mass index (BMI)-SDS in children with both T1D and CD. METHODS: Cross-sectional study in children registered in the international SWEET database in November 2020. Inclusion criteria were children (2-18 years) with T1D and CD with available data on treatment modality (CSII and injections therapy, IT), triglyceride, total cholesterol, HDL, LDL, dyslipidemia, HbA1c, and BMI-SDS. Overweight/obesity was defined as > +1 BMI-SDS for age. Data were analyzed by linear and logistical regression models with adjustment for age, gender, and diabetes duration. RESULTS: In total 1009 children with T1D and CD (female 54%, CSII 54%, age 13.9 years ±3.6, diabetes duration 7.2 years ±4.1, HbA1c 7.9% ±1.4) were included. Significant differences between children treated with CSII vs. IT were respectively found; HDL 60.0 mg/dL vs. 57.8 mg/dL, LDL 89.4 mg/dL vs. 94.2 mg/dL, HbA1c 7.7 vs. 8.1%, BMI-SDS 0.4 vs. 0.6, overweight and obesity 17% vs. 26% (all p < 0.05). CONCLUSIONS: CSII is associated with higher HDL and lower LDL, HbA1c, BMI-SDS, and percentage of overweight and obesity compared with IT in this study. Further prospective studies are required to determine whether CSII improves lipid profile, metabolic control and normalize body weight in children with both T1D and CD.

The Usefulness of Genotyping of Celiac Disease-Specific HLA among Children with Type 1 Diabetes in Various Clinical Situations.

Aim: The aim of the study was to determine the usefulness of HLA DQ2/DQ8 genotyping in children with T1D in various clinical situations: as a screening test at the diabetes onset, as a verification of the diagnosis in doubtful situations, and as a test estimating the risk of CD in the future. Materials and methods. Three groups of patients with T1D were included: newly diagnosed (n = 92), with CD and villous atrophy (n = 92), with CD and villous atrophy (n = 92), with CD and villous atrophy (n = 30), and with potential CD (n = 23). Genetic tests were performed (commercial test, PCR, and REX), and clinical data were collected. Results: The results of genetic tests confirmed the presence of DQ2/DQ8 in 94% of children with diabetes (group I) and in 100% of children with diabetes and CD (groups II and III, respectively). Comparative analysis of the HLA DQ2/DQ8 distribution did not show any differences. Allele DRB1∗04 (linked with HLA DQ8) was significantly less common in children with diabetes and CD (group I versus groups II and III, 56.5% vs. 24.5%; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529. Conclusions: Genotyping HLA DQ2/DQ8 as a negative screening has limited use in assessing the risk of CD at the diabetes onset and does not allow to verify the diagnosis of CD in doubtful situations. The presence of the DRB1∗04 allele modulates the risk of CD and significantly reduces it and can predict a potential form.

How does a predictive low glucose suspend (PLGS) system tackle pediatric lifespan challenges in diabetes treatment? Real world data analysis.

OBJECTIVES: The aim of the study was to assess the benefits of a predictive low glucose suspend (PLGS) system in real-life in children and adolescents with type 1 diabetes of different age and age-related clinical challenges. METHODS: Real life retrospective and descriptive analysis included 44 children (26 girls) with type 1 diabetes who were introduced to PLGS system. We divided them in three age groups: I (3-6 years old, n = 12), II (7-10 y/o, n = 16), III (11-19 y/o, n = 16). All children and their caregivers received unified training in self-management during PLGS therapy. Patients' data included: age, HbA1C levels, sex. While from the CGM metric, we obtained: time of sensor use (SENSuse), time in range (TiR): in, below and over target range and average blood glycemia (AVG), insulin suspension time (INSsusp). RESULTS: SENSuse was 93% in total, with 92%, 94%, and 87% in age groups I, II, III, respectively. In total the reduction of mean HbA1C from 7.61% to 6.88% (P < .05), while for the I, II, and III it was 7.46% to 6.72%, 6.91% to 6.41%, and 8.46 to 7.44%, respectively (P < .05). Although we observed a significant reduction of HbA1C, the time below target range was minimal. Specific findings included: group I-longest INSsusp (17%), group II-lowest glycemic variability (CV) (36%), and group III-highest AVG (169 mg/dL). There was a reverse correlation between suspend before low and age (-0.32, P < .05). In group I CV reduced TiR in target range (TiRin) (-0.82, P < .05), in group II use of complex boluses increased TiRin (0.52, P < .05). In group III higher CV increased HbA1C (0.64, P < .05) while reducing TiRin (-0.72, P < .05). CONCLUSIONS: PLGS is a suitable and safe therapeutic option for children with diabetes of all age and it is effective in addressing age-specific challenges. PLGS improves glycemic control in children of all age, positively affecting its different parameters.

Remission phase in children diagnosed with type 1 diabetes in years 2012 to 2013 in Silesia, Poland: An observational study.

BACKGROUND/OBJECTIVE: The study aimed to analyze the frequency of partial remission (PR) and its association with chosen clinical and laboratory factors among pediatric patients with newly diagnosed type 1 diabetes (T1D). The long-term effect of PR on chosen parameters was also investigated. METHODS: In 194 patients (95 girls) aged 8.1 ± 4.3 years, we analyzed data at T1D onset: glycemia, pH, C-peptide, antibodies, weight, and concomitant autoimmune diseases. Anthropometric parameters, daily insulin requirement (DIR), and HbA1c 2 and 4 years after T1D diagnosis were also analyzed. We determined PR based on HbA1c and DIR measurements at least every 3 months. RESULTS: PR occurred in 59% of patients. Remitters had significantly higher pH (7.33 vs 7.28, P = 0.03), weight SD score (SDS) (0.25 vs -0.24, P = 0.002), and body mass index SDS (0.19 vs -0.66, P = 0.02) compared with non-remitters. Concomitant diseases correlated negatively with PR. Multivariate analysis indicated only pH at onset was an independent predictor of PR. pH was the most important factor associated with the beginning of PR. There was a positive correlation between the start and duration of PR. Four years after T1D onset remitters had lower HbA1c (7.24% vs 8.05%, 53 vs 63.9 mmol/mol, P < 0.001) and DIR (0.81 vs 1.08, P = 0.005). CONCLUSIONS: PR occurred quite often and developed more frequently in children with higher: weight and BMI SDS, but the main factor influencing PR presence and duration was higher pH at T1D onset. There was a beneficial impact of PR on HbA1c and DIR after 4 years of treatment.

The usefulness of the FlashStyle Libre system in glycemic control in children with type 1 diabetes during summer camp.

THE AIM OF THE STUDY: was to evaluate the usefulness of Flash FreeStyle Libre in glycemic control in children during summer camp on the basis of the participants' completed questionnaire and on the basis of the assessment o the suitability of the system performed by medical staff based on a comparative analysis: glycemia by sensor and glucometer. MATERIAL AND METHODS: A study using the new Flash FreeStyle Libre glycemic control system was conducted at a seaside summer camp for children with diabetes at the seaside. The study included 75 children (32 boys and 43 girls), in mean 13.4 (SD 4.6) years old, with an average duration of diabetes of 6.5 (SD 4.5) years and mean HbA1c of 7.81% (SD 2.05). All camp participants were provided with Libre sensors, however, routine glucose control measurements with therapeutic decisions was made using traditional glucose meters. On the last day of the camp, after the removal of the sensors, a satisfaction survey was conducted to assess with a new self-monitoring method and a comparative analysis of the glucose results from the sensor with the personal glucose meters - MARD, MAD, and clinical errors on the Clarke Error Grid were calculated. RESULTS: In the Libre user's survey, wearing comfort and ease of installation were described as very good / good by 86% and 94% of the respondends, respectively. Ease of reading blood glucose by scan was positively evaluated by 92% of the respondents, 95% of the subjects did not report any side effects. The sensor remained intact for 14 days in 46 children (62%), which value was the basis for the statistical calculations. Comparative analysis of glucose results obtained from Libre measurements performed with glucose meters (3143 measurements) showed a relatively good MARD index - 18.22% on average, with a large individual variation (6.36-29.51%). Clarke Error Grid showed that 75.2% (2309) of the results were in Zone A (Acceptable Errors) and 95.81% (3012) in Zone A and B (Non-Negative Errors). CONCLUSION: Libre user's satisfaction survey revealed that most of the respondents rated the cooperation with Flash FreeStyle Libre positively. The relatively good results of Libre in comparison with glucose meters have confirmed the usefulness of this method of monitoring glucose in summer camps for children with diabetes.

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.

How modern technologies improve daily diabetic control.

INTRODUCTION: Diabetic children who live surrounded by modern technologies such as Facebook, Google, and GPS want their treatment to stand up to the times, especially if it accompanies them for their whole life. AIM OF THE STUDY: In this review we aim to analyse which technologies help diabetics in their everyday struggle to keep up with diabetes as well as whether those inventions catch up to the reality of 21st century. MATERIAL AND METHODS: We decided to discuss the most outstanding inventions in the field of diabetology. We chose insulin pumps, constant glucose monitoring (CGM) systems, mobile apps, and, last but not least, social media and the Internet as the most promising and fastest developing areas. Thanks to all of these technologies and devices we are now able to monitor patients all time. We have to take into account that the limitations of technology, the possibility of technical malfunction, and human error might prove to be fatal. CONCLUSIONS: To sum up, technology simplifies treatment and aids patients in daily diabetic control.

[Myasthenia gravis, Graves-Basedow disease and other autoimmune diseases in patient with diabetes type 1 - APS-3 case report, therapeutic complications]. / Miastenia, ch. Gravesa-Basedowa i inne zaburzenia autoimmunizacyjneu pacjentki z cukrzyca typu 1 ­ prezentacja przypadku APS-3, trudnosciterapeutyczne.

Diabetes type 1(T1D) is the most frequent form of diabetes in children and young people, which essence is autoimmune destruction of pancreatic B cells islet. Co-occurrence of other autoimmune diseases is observed in children with T1D, the most often are: Hashimoto disease or coeliac disease. We report the case of the patient, who presents coincidence of T1D with other rare autoimmune diseases such as: Graves - Basedow disease, myasthenia gravis, vitiligo and IgA deficiency. All mentioned diseases significantly complicated both endocrine and diabetic treatment of our patient and they negatively contributed her quality of life. The clinical picture of the case allows to recognize one of the autoimmune polyendocrine syndromes: APS-3 and is associated with still high risk of developing another autoimmune disease.

Lipid Profile in Adolescent Girls with Type 1 Diabetes Mellitus and Hyperandrogenemia.

Study Objectives. The study aim was to evaluate whether hyperandrogenemia in adolescent girls with type 1 diabetes mellitus (T1DM) may adversely influence lipid profile. Design and Participants. Lipid levels in 16 diabetic girls with biochemical hyperandrogenemia (T1DM-H) aged 16.3 ± 1.2 years were compared to 38 diabetic girls with normal androgen levels (T1DM-N) aged 15.8 ± 1.2 years. 15 healthy girls served as controls (CG). In all patients, anthropometric measurements were done, and androgens and SHBG were assessed. Results. In T1DM-H, total cholesterol (TC) and low density cholesterol (LDL-ch) were significantly higher than in CG (196.1 ± 41.2 versus 162.7 ± 31.7 mg/dL, p = 0.01; 117.3 ± 33.1 versus 91.3 ± 27.8 mg/dL, p = 0.01, resp.). Their LDL-ch, non-high density cholesterol (non-HDL-ch) concentrations, and LDL/HDL ratio were also significantly higher than in T1DM-N (117.3 ± 33.1 versus 97.7 ± 26.7 mg/dL, p = 0.03; 137.3 ± 42.9 versus 113.3 ± 40.4 mg/dL, p = 0.04; 2.8 ± 3.7 versus 1.6 ± 0.5, p = 0.04, resp.). In stepwise multiple linear regression, free androgen index (FAI) and waist-to-hip ratio (WHR) were associated with TC (R (2) = 0.4, p < 0.0006), non-HDL-ch (R (2) = 0.4, p < 0.0003), and LDL-ch (R (2) = 0.4, p < 0.0008). Triglycerides and LDL/HDL ratio were (R (2) = 0.7, p < 0.0001, R (2) = 0.6, p < 0.0003 resp.) related to testosterone, FAI, WHR, and mean HbA1c. Conclusion. Lipid profile in diabetic adolescent girls is adversely influenced by the androgens level, particularly in the group with higher WHR and poorer glycemic control.

Dysglycemia in critically ill children.

Stress hyperglycemia remains a significant and unsolved medical condition in critically ill children. Treatment for hyperglycemia is controversial and, to date, no recommendations exist from pediatric professional society regarding the management of hyperglycemia in critically ill children. This review summarizes recent work investigating the pathogenesis of stress hyperglycemia, the importance of hypoglycemic episodes and glycemic variability among critically ill patients.

[Humoral response markers in GCK MODY]. / Markery reakcji humoralnej w cukrzycy GCK MODY.

BACKGROUND: The prevalence of antibodies to pancreatic islets in monogenic diabetes remains unknown and the incidence estimation is difficult as the occurrence of autoantibodies in patient is one of the well-known exclusion criteria for further genetic diagnostics. They has been found not only among patients with type 1 diabetes, but also in other types of diabetes: Type 2 diabetes, Latent Autoimmune Diabetes in Adults (LADA) (16) and monogenic diabetes (MD). AIM: Immunological characteristic of GCK MODY patients. METHODS: The study group included families of 27 adolescent patients with GCK MODY (39 parents and 19 siblings) monitored in the Department of Pediatrics, Endocrinology and Diabetes and in the Diabetes Clinic of John Paul II Upper Silesian Child Health Centre in Katowice in the years 2007-2012. All patients and family members with GCK MODY underwent a blood sample drawing for immunological (classic humoral response markers: ICA, GAD, IA-2, IAA) and biochemical diagnostics. Pediatric, diabetes and family medical history was collected from the subjects and parents. RESULTS: Immunological diagnostics was performed in all patients except 1 (96.3%). Immunological diagnostics included 17 (89.5%) parents and 7 (87.5%) siblings with diagnosed GCK MODY. 8 (30.8%) adolescent patients with GCK MODY, 3 subjects (17.64%) among parents (with GCK MODY), as well as 2 subjects (28.57%) among siblings (with GCK MODY) showed a positive antibodies screen. CONCLUSION: The results of our study in children with GCK MODY and their family members suggest that the occurrence of classic antibodies directed against pancreatic islets antigens is fairly common in patients with GCK MODY. Despite various observations and many legitimate discussions, it is difficult to clarify the pathogenesis of the occurrence of autoantibodies in monogenic diabetes.

Genetic counseling in monogenic diabetes GCK MODY.

INTRODUCTION: Genetic testing in families with monogenic GCK MODY has predictive, diagnostic, and preventive utility. Predictive tests relate to people who have no features of the disorder themselves at the time of testing. Diagnostic tests relate to family members who have been previously diagnosed with diabetes mellitus or glucose metabolism disturbances. The preventive value of genetic testing for families is to raise awareness of the circumstances leading to glucose metabolism disorders. AIM: The detection of mutation carriers among family members of patients with GCK MODY and the determination of the clinical significance of the genetic test result. METHODS: The study group included 27 families of adolescent patients with GCK MODY (39 (75%) of parents and 19 (73.08%) of siblings) monitored in the Department of Pediatrics, Endocrinology and Diabetes and in the Diabetes Clinic of John Paul II Upper Silesian Child Health Centre in Katowice in the years 2007-2012. Subjects underwent a blood sample drawing for genetic and biochemical testing. RESULTS: Through the genetic diagnostics we diagnosed GCK MODY in 14 (63.64%) mothers, 6 (35.29%) fathers and in 7 (36,84%) siblings. Genetic testing has contributed to the detection of 7 (26.92%) asymptomatic carriers of GCK gene mutation among parents and 3 (15,79%) asymptomatic carriers among siblings declaring no carbohydrate metabolism disturbances (before genetic testing there were no indications suggesting carbohydrate metabolism disturbances; OGTT were performed after positive genetic testing). CONCLUSIONS: Each case of mutation detection, which is the cause of monogenic diabetes in a patient, justifies the genetic testing in other members of his/her family. Awareness of the genetic status may allow sick family member to confirm the diagnosis, while asymptomatic mutation carriers could benefit from an early clinical observation. Consequently, in each case it gives an opportunity to take diagnostic and therapeutic measures in accordance with the current state of knowledge.

Differential sequential patterns supporting insulin therapy of new-onset type 1 diabetes.

BACKGROUND: In spite of numerous research efforts on supporting the therapy of diabetes mellitus, the subject still involves challenges and creates active interest among researchers. In this paper, a decision support tool is presented for setting insulin therapy in new-onset type 1 diabetes. METHODS: The concept of differential sequential patterns (DSPs) is introduced with the aim of representing deviations in the patient's blood glucose level (BGL) and the amount of insulin injections administered. The decision support tool is created using data mining algorithms for discovering sequential patterns. RESULTS: By using the DSPs, it is possible to support the physician's decisionmaking concerning changing the treatment (i.e., whether to increase or decrease the insulin dosage). The other contributions of the paper are an algorithm for generating DSPs and a new method for evaluating nocturnal glycaemia. The proposed qualitative evaluation of nocturnal glycaemia improves the generalization capabilities of the DSPs. CONCLUSIONS: The usefulness of the proposed approach was evident in the results of experiments in which juvenile diabetic patients actual data were used. It was confirmed that the proposed DSPs can be used to guide the therapy of numerous juvenile patients with type 1 diabetes.

Incidence of type 1 diabetes among Polish children ages 0-14 years from 1989-2012.

AIMS: The incidence of pediatric type 1 diabetes mellitus (T1DM) in Poland is intermediate relative to the rest of the world. T1DM prevalence in the region of Silesia approximates national estimates for all of Poland. This epidemiologic study aimed to analyze the changes in incidence rates of T1DM among children ages 0-14 years from 1989 to 2012 in this region. METHODS: Data collection methods for the registry followed EURODIAB criteria. To estimate overall population size, data from the Central and regional Statistical Office in Katowice were used. T1DM incidence rates/100,000 children ages 0-14 years/annum and their 95 % CI were calculated for all children and in age subgroups (0-4, 5-9, 10-14 years). For comparative analysis incidence rates were age and sex standardized to the population of Poland in 2005. For statistical analyses open source R Bioconductor software was used. RESULTS: During this 24-year period, 2,215 new cases (1,146 boys) were diagnosed. The standardized incidence rate rose about 7 % annually. The mean standardized incidence rates estimated in four 6-year time periods (1989-1994, 1995-2000, 2001-2006, 2007-2012) separately showed significant increases from 5.80/100,000/year (1989-1994) through 10.44/100,000/year (1995-2000) and 15.05/100,000/year (2001-2006) to 18.94/100,000/year (2007-2012). From 1989 to 2012, the greatest relative rise in annual incidence (/100,000/year) was among the very young: 2.58-14.00 (0-4 years); 4.96-19.43 (5-9 years); 8.84-22.15 (10-14 years). The highest average annual increment of the incidence rate was in the middle age subgroup (5-9 years). No significant sex difference was observed. CONCLUSIONS: The overall incidence rate increased 3.8 times, suggesting an epidemic of pediatric T1DM in Silesia, Poland. These temporal changes confirm that Poland currently has one of the highest incidence rates of pediatric T1DM in Europe.

GATA4 mutations are a cause of neonatal and childhood-onset diabetes.

The GATA family zinc finger transcription factors GATA4 and GATA6 are known to play important roles in the development of the pancreas. In mice, both Gata4 and Gata6 are required for pancreatic development. In humans, GATA6 haploinsufficiency can cause pancreatic agenesis and heart defects. Congenital heart defects also are common in patients with GATA4 mutations and deletions, but the role of GATA4 in the developing human pancreas is unproven. We report five patients with deletions (n = 4) or mutations of the GATA4 gene who have diabetes and a variable exocrine phenotype. In four cases, diabetes presented in the neonatal period (age at diagnosis 1-7 days). A de novo GATA4 missense mutation (p.N273K) was identified in a patient with complete absence of the pancreas confirmed at postmortem. This mutation affects a highly conserved residue located in the second zinc finger domain of the GATA4 protein. In vitro studies showed reduced DNA binding and transactivational activity of the mutant protein. We show that GATA4 mutations/deletions are a cause of neonatal or childhood-onset diabetes with or without exocrine insufficiency. These results confirm a role for GATA4 in normal development of the human pancreas.

Hyperandrogenism in adolescent girls with type 1 diabetes mellitus treated with intensive and continuous subcutaneous insulin therapy.

INTRODUCTION: Women with type 1 diabetes mellitus (T1DM) experience high prevalence of hyperandrogenic disorders. The aim of this study was to evaluate hormonal profile with respect to hyperandrogenic disorders in adolescents with T1DM. MATERIAL AND METHODS: Forty seven adolescent girls with T1DM were evaluated and compared to 19 healthy and 21 non-diabetic girls with polycystic ovary syndrome (PCOS). In all subjects, basal and GnRH analogue stimulated androgens, gonadotropins and SHBG were measured and ultrasonography of ovaries was performed. RESULTS: Girls with T1DM experienced first menses significantly later than healthy controls [13.1 (12.0-14.0) v. 12.0 (11.0-12.0) years, p = 0.02]. Nine (19.2%) of them fulfilled PCOS criteria (T1DM+PCOS). They had significantly mean HbA1c from the diagnosis of T1DM than T1DM girls with no PCOS [6.7 (6.6-7.2) v. 7.3(6.4-7.8)%, p = 0.049]. Hormonal profile, hirsutism score and ovarian volume did not differ significantly between the two groups. HbA1c at the study point and mean HbA1c for the last 12 months correlated negatively with SHBG level (r = -0.5, p = 0.006; r = -0.04, p = 0.02). T1DM+PCOS girls had significantly lower FAI [3.0 (2.6-4.3) v. 8.6 (6.5-10.8), p = 0.04] and ovarian volume than non-diabetic PCOS girls [4.6 (2.7-5.2) v. 7.4 (4.3-10.0) mL, p = 0.007]. CONCLUSIONS: Clinical symptoms of PCOS in adolescent girls with T1DM are milder than in non-diabetic peers, probably due to the protective role of higher SHBG resulting in lower free androgen level.

Quantitative ultrasound bone measurements in pre-pubertal children with type 1 diabetes.

This case-control study aimed to assess bone status in children with type 1 diabetes mellitus (T1DM). Fifty-seven pre-pubertal patients (37 boys, aged 7.9 ± 2.5 years, T1DM duration 3.1 ± 1.6 years) and 171 age-matched healthy controls (111 boys) were studied. Quantitative ultrasound (QUS) was used to measure amplitude dependent speed of sound (Ad-SoS) at hand phalanges (expressed as standard deviation score [SDS]). Anthropometric and disease-related data (including mean HbA(1c) from whole T1DM duration [T], last year [Y], examination day [D]) were collected. Mean Ad-SoS SDS in patients -0.13 ± 1.32 (95% confidence interval [CI] -0.48, 0.22) was similar to that of controls. Subgroups discriminated according to HbA(1c) D, Y and T (cut-off 7.0%) did not differ regarding analyzed parameters. In patients, Ad-SoS SDS was comparable for both genders. Multivariable stepwise regression analysis showed significant negative influence of diabetes duration on Ad-SoS SDS. QUS findings in pre-pubertal children with T1DM do not differ from those in healthy children. Disease duration seems to affect negatively Ad-SoS SDS. However, independent prospective studies are needed to elucidate the true associations.