The Use of a Hybrid Closed-Loop System for Glycemic Control in Two Pediatric Patients with Type 1 Diabetes Undergoing Minor Surgery.

Technological progress in the treatment of type 1 diabetes requires doctors to use modern methods of insulin therapy in all areas of medicine that patients may come into contact with, including surgical interventions. The current guidelines indicate the possibility of using continuous subcutaneous insulin infusion in minor surgical procedures, but there are few reported cases of using a hybrid closed-loop system in perioperative insulin therapy. This case presentation focuses on two children with type 1 diabetes who were treated with an advanced hybrid closed-loop (AHCL) system during a minor surgical procedure. In the periprocedural period, the recommended mean glycemia and the time in range were maintained.

Severe malnutrition as a cause of transient carbohydrate metabolism disorders which evolved into hyperosmolar hyperglycaemic state.

The hyperosmolar hyperglycaemic state (HHS) is a very severe condition characterised by hyperosmolality, hyperglycaemia and dehydration without significant ketosis. The article presents the case of a 14.5-year-old cachectic patient with diagnosed HHS. Appropriate treatment per the ISPAD Guidelines was implemented. After metabolic stabilisation was achieved, the patient was transferred for further treatment to the Pediatric Gastroenterology Department due to her life-threatening cachexia. Normal glucose levels were observed during hospitalisation and the patient required no further insulin supplementation. Unfortunately, two months after discharge from hospital, the patient suffered sudden death at home. The patient did not live until full diabetological diagnostics could be performed. The transient hyperglycaemia may have been caused by a very early stage of type 1 diabetes (pre-diabetes), malnutrition-related diabetes mellitus (MRDM) or stress-induced hyperglycaemia (SIH). The case demonstrates that HHS can develop not only secondary to diabetes, but also be a severe complication of transient carbohydrate metabolism disorders in the course of cachexia.

Reference Ranges of Glycemic Variability in Infants after Surgery-A Prospective Cohort Study.

We aimed to define reference ranges of glycemic variability indices derived from continuous glucose monitoring data for non-diabetic infants during post-operative intensive care treatment after cardiac surgery procedures. We performed a prospective cohort intervention study in a pediatric intensive care unit (PICU). Non-diabetic infants aged 0-12 months after corrective cardiovascular surgery procedures were fitted upon arrival to the PICU with a continuous glucose monitoring system (iPro2, Medtronic, Minneapolis, MN, USA). Thirteen glycemic variability indices were calculated for each patient. Complete recordings of 65 patients were collected on the first postoperative day. During the first three postsurgical days 5%, 24% and 43% of patients experienced at least one hypoglycemia episode, and 40%, 10% and 15%-hyperglycemia episode, respectively, in each day. Due to significant differences between the first postoperative day (mean glycemia 130 ± 31 mg/dL) and the second and third day (105 ± 18 mg/dL, 101 ± 22.2 mg/dL; p < 0.0001), we proposed two separate reference ranges-for the acute and steady state patients. Thus, for individual glucose measurements, we proposed a reference range between 85 and 229 mg/dL and 69 and 149 mg/dL. For the mean daily glucose level, ranges between 122 and 137 mg/dL and 95 and 110 mg/dL were proposed. In conclusion, rt-CGM revealed a very high likelihood of hyperglycemia in the first postsurgical day. The widespread use of CGM systems in a pediatric ICU setting should be considered as a safeguard against dysglycemic episodes; however, reference ranges for those patients should be different to those used in diabetes care.

Thyroid diseases - ally or enemy of type 1 diabetes in children and adolescents?

INTRODUCTION: Autoimmune thyroid diseases (AIT) are one of the most common disorders associated with type 1 diabetes (T1D) and they are capable of influencing its course. For Hashimoto's lymphocytic thyroiditis, the incidence is 14-28%, while for Graves-Basedow hyperthyroidism it is 0.5-7%. Aim of the study: Assessment of type 1 diabetes in the pediatric population with coexisting autoimmune thyroid diseases: Hashimoto's lymphocytic thyroiditis and Graves-Basedow's disease. MATERIAL AND METHODS: Analyzing publications from the PubMed scientific database from 1990 to May 2020. RESULTS: Among pediatric patients with T1D and coexisting thyroid autoimmunity insufficient glycemic control is usually observed. Reported average increase in glycated hemoglobin concentration ranges from 7.9 to 9.2%. In children with T1D and subclinical hypothyroidism, an increased number of episodes of hypoglycemia was noted - 5 vs. 2 episodes per year among children with euthyroidism. In hyperthyroidism patients the number of episodes of hypoglycemia was 34.4 vs. 17.2 per 100 incidents in euthyroidism patients. An increased occurrence of diabetic ketoacidosis events may also be observed - 18.1 vs. 7.7 per 100 patients with euthyroidism per year. The risk of developing chronic complications in the form of cardiovascular diseases is also higher. However, basing on the available literature, this subject is still debatable. CONCLUSIONS: Autoimmune thyroid diseases often accompany and interfere with type 1 diabetes in children and adolescents. Paying special attention to the different course of diabetes in the presence of thyroid disorders is an important and essential element of diabetes care.

[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.

Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes.

BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 106/kg b.w. of autologous expanded CD3+CD4+CD25highCD127- Tregs. RESULTS: The disease progressed and all patients were insulin-dependent 2 years after inclusion. The ß-cell function measured by c-peptide levels and the use of insulin were the best preserved in patients treated with two doses of Tregs (3/6 in remission), less so after one dose (1/6 in remission) and the worst in untreated controls (no remissions). Increased levels of Tregs could be seen in peripheral blood after their adoptive transfer together with the shift from naïve CD62L+CD45RA+ to memory CD62L+CD45RA- Tregs. Increasing serum levels of proinflammatory cytokines were found: IL6 increased in all subjects, while IL1 and TNFα increased only in untreated group. Therapeutic Tregs were dependent on IL2, and their survival could be improved by other lymphocytes. CONCLUSIONS: The disease progression was associated with changing proportions of naïve and memory Tregs and slowly increasing proinflammatory activity, which was only partially controlled by the administered Tregs. The therapeutic cells were highly dependent on IL2. We conclude that the therapy should be administered at the earliest to protect the highest possible mass of islets and also to utilize the preserved content of Tregs in the earlier phases of T1DM. Trial registration http://www.controlled-trials.com/ISRCTN06128462 ; registered retrospectively.

Differential regulation of serum microRNA expression by HNF1ß and HNF1α transcription factors.

AIMS/HYPOTHESIS: We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1ß transcription factor, and investigate whether its effect manifests in serum. METHODS: The Polish cohort (N = 60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 with GCK-MODY, an HbA1c-matched type 1 diabetic group (n = 9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort. The Polish cohort underwent miRNA serum level profiling with quantitative real-time PCR (qPCR) arrays to identify differentially expressed miRNAs. Validation was performed using qPCR. To determine whether serum content reflects alterations at a cellular level, we quantified miRNA levels in a human hepatocyte cell line (HepG2) with small interfering RNA knockdowns of HNF1α or HNF1ß. RESULTS: Significant differences (adjusted p < 0.05) were noted for 11 miRNAs. Five of them differed between HNF1A-MODY and HNF1B-MODY, and, amongst those, four (miR-24, miR-27b, miR-223 and miR-199a) showed HNF1B-MODY-specific expression levels in the replication group. In all four cases the miRNA expression level was lower in HNF1B-MODY than in all other tested groups. Areas under the receiver operating characteristic curves ranged from 0.79 to 0.86, with sensitivity and specificity reaching 91.7% (miR-24) and 82.1% (miR-199a), respectively. The cellular expression pattern of miRNA was consistent with serum levels, as all were significantly higher in HNF1α- than in HNF1ß-deficient HepG2 cells. CONCLUSIONS/INTERPRETATION: We have shown that expression of specific miRNAs depends on HNF1ß function. The impact of HNF1ß deficiency was evidenced at serum level, making HNF1ß-dependent miRNAs potentially applicable in the diagnosis of HNF1B-MODY.

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management?

INTRODUCTION: Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient's characteristics and response to pharmacotherapy. MATERIAL AND METHODS: Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30). RESULTS: CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed. CONCLUSIONS: Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications.

How does autoimmune thyroiditis in children with type 1 diabetes mellitus influence glycemic control, lipid profile and thyroid volume?

AIM: To investigate whether autoimmune thyroiditis (AIT) in children with type 1 diabetes mellitus (DM1) has any influence on glycemic control, lipid profile or thyroid volume. METHODS: A total of 330 patients with DM1 and AIT (DM1+AIT group) were compared with 309 children with DM1 without AIT (control group). Patients were treated in four Polish academic pediatric diabetes centers from 2008 to 2012: Warsaw, Lodz, Katowice and Gdansk. All patients underwent measurements of thyroid-stimulating hormone (TSH), free thyroxine, anti-thyroid peroxidase (anti-TPO) antibody, anti-thyroglobulin (anti-TG) antibody and HbA1c levels, and thyroid ultrasound examination. RESULTS: Among AIT+DM1 patients, 62% (n=205) were female, whereas in the control group 60.8% (n=188) were male (p<0.0001). Children with AIT+DM1 had lower a BMI-SDS (mean difference of -0.5, 95% CI -0.68 to -0.33; p<0.0001), had a higher SDS thyroid volume (0.27, 95% CI 0.03-0.51; p=0.014) and needed less insulin (-0.15, 95% CI -0.20 to -0.11 U/kg body weight per day; p<0.0001) in comparison with the control group. AIT patients had higher HbA1c levels (0.66, 95% CI 0.36%-0.96%, p<0.0001), lower HDL-cholesterol levels (-3.68, 95% CI -1.41 to -5.94 mg/dL, p=0.002) and higher triglyceride levels (7.16, 95% CI 1.22-13.10 mg/dL, p=0.02). Patients with positive anti-TPO and anti-TG antibodies were older (by 1.95 years, 95% CI 0.98-2.92 years, p=0.006) and had longer DM1 duration (by 1.64 years, 95% CI 0.76-2.52 years, p=0.006). Presence of anti-TPO antibodies was associated with higher TSH levels (odds ratio 2.34, 95% CI 1.36-4.04; p=0.007). CONCLUSION: AIT accompanying DM1 is associated with worse glycemic control and lipid profile as well as a lower daily insulin requirement. The female gender is more likely to develop AIT and hypothyroidism.

The prevalence of Wolfram syndrome in a paediatric population with diabetes.

INTRODUCTION: Wolfram syndrome (WFS) is the most frequent syndromic form of monogenic diabetes coexisting with optic atrophy and many other disorders. The aim of this study was to estimate the prevalence of Wolfram syndrome among children with diabetes in Poland. MATERIAL AND METHODS: These calculations were performed among Polish diabetic children, aged 0-18 years, from three administrative regions between January 2005 and December 2011. Epidemiological data was obtained by matching the results from the EURO-WABBPoland Project and the PolPeDiab Registry. RESULTS: Throughout the study period, we confirmed genetic diagnosis of Wolfram syndrome in 13 patients from Poland. Three patients originated from the studied regions with complete epidemiological data on paediatric diabetes. The total number of patients with diagnosed diabetes in the study equalled 2,568 cases. The prevalence of Wolfram syndrome among Polish children with diabetes is 0.12% (95% Confidence Interval 0.04-0.34%). CONCLUSIONS: We estimate that Wolfram syndrome is: 26 to 35 times less frequent than monogenic diabetes (MODY and neonatal diabetes) in the Polish paediatric population.

Management of familial hypercholesterolemia in children and adolescents. Position paper of the Polish Lipid Expert Forum.

Familial hypercholesterolemia (FH) affects on average 1 in 500 individuals in European countries, and it is estimated that FH in Poland may affect more than 80,000 people. However, in Poland, only about 20% of the population is estimated to have been diagnosed with FH, of which only a small number receive adequate treatment. FH results in more rapid development of atherosclerosis and is associated with a high risk of cardiovascular events. Atherosclerosis develops beginning in childhood in patients with FH and reaches advanced stages before clinical manifestations develop. Inadequate diagnostics and treatment of FH in Polish children suggests a need for raising the level of awareness and understanding of the condition in both society and among health professionals. These recommendations present the current epidemiological status, guidelines for diagnosing FH in Polish children and adolescents, and effective treatment options.

L-thyroxine stabilizes autoimmune inflammatory process in euthyroid nongoitrous children with Hashimoto's thyroiditis and type 1 diabetes mellitus.

OBJECTIVE: To investigate if L-thyroxine (T4) treatment may influence the clinical course of autoimmune thyroiditis (AIT) or prevent progression to subclinical or overt hypothyroidism in euthyroid nongoitrous pediatric patients with type 1 diabetes mellitus (T1DM) and AIT. METHODS: The study was performed in four Polish pediatric diabetes centers. Of 330 children with T1DM and AIT followed between 2008 and 2012, 101 received L-T4 and 160 underwent clinical observation for 24 months. Thyroid stimulating hormone (TSH), free T4 (fT4), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG), glycosylated hemoglobin (HbA1c) levels, and lipid profile were assessed in all patients. Ultrasonographic evaluation was also performed in all children at each examination. RESULTS: Patients treated with thyroid hormones had higher TSH levels (3.99; interquantile 3.5 to 4.52 vs. 2.09 mIU/L; interquantile 1.55 to 3.06; pp<0.0001). A fall in TSH level (0.87 mIU/L 95% CI 0.43-1.30; pp<0.0001) was documented after the first year of treatment. FT4 level did not differ between the groups at baseline (p=0.7434), but rose in the treatment group and fell in the control group [mean difference 0.78 95% CI-0.22-1.53 pmol/L (p=0.02) after 12 months and 0.98 95% CI 0.04-1.76 (p=0.005) after 24 months]. Higher levels of anti-TPO were initially found in the treated patients (pp<0.0001) and significantly decreased over the 24-month period (pp<0.0001). Children in the treatment group had higher anti-TG levels (pp<0.0001), which showed a borderline decrease (p=0.08) in time. In the control group, anti-TG levels rose marginally (p=0.06) during the study. CONCLUSIONS: The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.

[Coexistance of autoimmunological diseases with type 1 diabetes mellitus in young patients based on literature and own experience]. / Wspólwystepowania chorób autoimmunologicznych z cukrzyca typu 1 u mlodocianych chorych w oparciu o dane pismiennictwa i obserwacje wlasne.

Patients with autoimmune type 1 diabetes mellitus have often, besides immune diabetic markers, also other organ-specific antibodies. In many diabetic patients autoimmune thyroid diseases, i.e. Hashimoto thyroiditis and Grave's disease, with silent clinical course can be diagnosed. Because 50% of children with diabetes and significant titres of thyroid autoantibodies (ATA) develop thyroid problems within 3-4 years, examinations of thyroid antibodies should be performed yearly. In cases of significant antibody titres, thyroid function tests and ultrasound assessment are recommended in order to minimize the risk of undiagnosed hypothyroidism in these patients. Coeliac is an other disease commonly coexisting with type 1 diabetes mellitus and autoimmune thyroid diseases. It is recommended that screening for coeliac disease should be part of the routine investigation for all patients. Potential benefits of treatment coeliac disease is more prevalent in individuals with type 1 diabetes mellitus, and when untreated is associated with a number of medical complications, including poor glycaemic control. Identification of patients with coeliac has been facilitated in recent years by serological screening. Initial normal screening does not exclude coeliac and repeated screening is indicated, a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.

The assessment of autoimmunological status and prevalence of different forms of celiac disease among children with type 1 diabetes mellitus and celiac disease.

This study aims to assess the autoimmunological status and forms of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM). The study group comprises 27 patients at the mean age of 12.30 years (+/-SD 3.12). The measurement of the level of diabetes-specific antibodies and organ-specific antibodies was gained at the T1DM-onset and repeated annually. The following risk factors influencing time of CD diagnosis were analyzed: age, sex, T1DM duration, autoantibodies, and HLA-haplotype. The prevalence of antibodies was GADA-74%, IAA-63%, IA2A-67%, ATA-11%, and ATG-4%. The intestinal biopsy revealed in 19% no changes and in 77% stage 3 (Marsh scale). In most cases, no clinical manifestation of CD was observed. The diagnosis of Hashimoto's disease was made twice. The negative correlation between the age at T1DM-onset and the interval between onset of T1DM and CD (r = -0.35, p < .05) was noted. The high-comorbidity ratio of CD and thyroiditis with T1DM demands regular screening tests especially in the first years after T1DM-onset.

[Early metabolic abnormalities--insulin resistance, hyperinsulinemia, impaired glucose tolerance and diabetes, in adolescent girls with polycystic ovarian syndrome]. / Wczesne metaboliczne nieprawidlowosci--insulinoopornosc, hiperinsulinemia, zaburzenia tolerancji glukozy i cukrzyca u dziewczat z zespolem policystycznych jajników.

Polycystic ovary syndrome (PCOS), the main androgen disorder in women. Recently, it has been suggested that the condition is hereditary and that women with PCOS have disturbances, such as hyperandrogenism and additional metabolic abnormalities as hyperinsulinaemia, increased insulin resistance, dyslipidemia. Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS are at an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility. Furthermore, the physical signs of PCOS can be detrimental to a teenage girl's self-image. Early diagnosis and treatment of PCOS in adolescents are essential in ensuring adulthood health and restoring self-esteem. Treatment for an adolescent with PCOS includes diet and exercise, metformin, and oral contraceptive pills. Still, surgery is not indicated in teenagers. Furthermore, psychological factors must be taken into consideration as well.

Is the association between TNF-alpha-308 A allele and DMT1 independent of HLA-DRB1, DQB1 alleles?

The aim of the study was to assess chosen factors of genetic susceptibility to DMT1: DRB1, DQB1, and TNF-alpha polymorphisms-308 (G/A) in children with DMT1 and their up-to-now healthy siblings. Then we tested whether the association between TNF-alpha genes and DMT1 is independent of HLA. 87 diabetic children, their 78 siblings, and 85 persons from healthy control group were followed up. The highest risk of DMT1 was connected with alleles: DRB1*0401 (OR = 3.39; CI: 1.55-7.41), DRB1*0301 (OR = 2.72; CI: 1.48-5.01), DQB1*0201 (OR = 4.04; CI: 2.17-7.52), DQB1*0302 (OR = 5.08; CI: 2.54-10.14), and TNF-alpha-308 A allele (OR = 2.59; CI: 1.23-5.44). Moreover linkage disequilibrium for TNF-alpha-308 A allele with DRB1*0301 and DQB1*0201 was observed in both diabetic children and their siblings. Diabetic children and their siblings present similar genetic risk factors for DMT1. The association between TNF-alpha-308 A allele and DMT1 is dependent of HLA-DRB1 and DQB1 alleles.