Magnesium, zinc and iron serum levels as potential parameters significant for effective glycemic control in children with type 1 diabetes

Background. Various trace elements contribute to the development of diabetes and its complications through their roles in glucose metabolism and the oxidative stress response. The aim of this study was to ascertain the difference in serum magnesium, zinc and iron concentrations between healthy children and children with type 1 diabetes mellitus (T1DM). This study also aimed to determine whether serum concentrations of magnesium, zinc, and iron in children with T1DM correlated with the duration of the disease and the quality of glycemic control in this group. Material and methods. A total of 99 children with T1DM and 40 healthy children were included in this study. Magnesium, zinc and iron serum levels were assessed using the photometric method. Results. Significantly lower levels of magnesium and zinc (P < 0.001) were observed, between the T1DM group and the healthy control group but no statistically significant differences were found in iron levels (P = 0.13) between the two groups. While there were no statistically significant differences in serum concentrations with respect to the duration of disease, it was, however, discovered that children with poorer glycemic control had significantly lower serum zinc concentrations (P < 0.001) while magnesium and iron levels remained similar (P = 0.07 and 0.21 respectively). Conclusion. This study found that while there was no significant difference in iron serum levels in children with T1DM compared to healthy controls, children with T1DM did have more significantly decreased magnesium and zinc serum levels than the control group. Serum zinc levels in this study also directly correlated to poorer glycemic control. Further studies are required to explore whether magnesium and zinc supplementa­tion, or nutritional intake, could potentially be used to achieve better glycemic control in children with T1DM

ZINC AND B1-PROTEIN HIGH MOBILITY GROUPS IN CHILDREN WITH TYPE 1 MUMMARIES

Ciljevi: Cilj je ovog ispitivanja bio istražiti ulogu cinka i alarmina HMGB1 u razvitku šećerne bolesti tipa 1. Dokazana je uključenost proteina visoke mobilnosti iz skupine 1 (HMGB1) u raznim autoimunim i upalnim bolestima, međutim uloga ove proinflamatorne molekule kod djece sa šećernom bolesti tipa 1 (ŠBT1) nije do sada bila razjašnjena. Također je cilj bio usporediti razinu serumskog HMGB1 u djece u ranim fazama ŠBT1 (skupina 1) i onih s dužim trajanjem bolesti (skupina 2) s kontrolnom skupinom bez ŠBT1 ili drugih autoimunuh bolesti. Dizajn studije: Presječno ispitivanje Ispitanici: Ovo israživanje uključuje 141 dijete: skupina 1 (N = 28), skupina 2 (N = 73) i kontrolna skupina (N = 40). Materijali i metode: Mjerenja su uzeta iz seruma za sljedeće: HMGB1, cink, broj bijelih krvnih stanica, C-reaktivni protein, glukoza, hemoglobin A1C i β-stanična protutijela (GADA-65, IA-2, ICA). Rezultati: Djeca sa ŠBT1 imaju statistički značajno višu razinu serumskog HMGB1 (8,7 ug/L) u usporedbi s kontrolnom skupinom djece bez ŠBT1 (1,0 ug/L). Razina HMGB1 statistički je veća kod djece s dužim trajanjem bolesti (skupina 2: 8,7 ug/l, P < 0,001). Značajno nižu razinu cinka ima skupina djece sa ŠBT1 (10,7) u odnosu na kontrolnu skupinu (12,85). Usporedbom vrijednosti cinka s dužinom trajanja dijabetesa, značajno najnižu srednju vrijednost cinka (10,3 interkvartilnog raspona 9 – 11,7) imaju ispitanici kojima dijabetes traje duže od dvije godine. Zaključak: Viša razina HMGB1 u djece s ŠBT1 ukazuje na to da ova proinflamatorna molekula može poslužiti kao biomarker upale kod bolesnika s dijabetesom i može biti bolji marker u usporedbi s drugim reaktantima upale.Objectives: The aim of this study was to investigate the role of zinc and HMGB1 alarmin in the development of Type 1 diabetes. The involvement of the high-mobility group box 1 pro- tein (HMGB1) in various autoimmune and inflammatory diseases has been documented be- fore. However, the role of this proinflammatory molecule in children with diabetes type 1 (T1DM) has not been clarified so far. The aim of this study was to compare the level of serum HMGB1 in children within the early (Group 1) and late (Group 2) stages of T1DM, with the control group of children without T1DM or any other autoimmune disease. Study design: A cross-sectional study. Participants: The study included 141 children: Group 1 (N=28), Group 2 (N=73) and Con- trol group (N=40). Materials and Methods: The measurements were made on serum samples for: HMGB1, zinc, white blood cell count, C-reactive protein, glucose, haemoglobin A1C, and β-cells autoanti- bodies (GADA-65, IA-2, ICA). Results: The children with T1DM had a statistically significant higher serum levels of HMGB1 (experimental group: 8.7 µg/l) compared to the children without T1DM (control group: 1.0). The HMGB1 level was statistically higher in children with a longer disease dura- tion (Group 1: 4.9 µg/l; Group 2: 8.7 µg/l, P <0.001). The children with T1DM had signifi- cantly lower zinc levels (10.7) compared to the control group (12.85). Comparing the zinc values according to the duration of diabetes, the subjects with diabetes which lasts for more than two years have the significantly lowest mean zinc levels (10.3 of the interquartile range 9 – 11.7). Conclusion: The higher level of HMGB1 in children with T1DM indicates that this proin- flammatory molecule can serve as an inflammatory biomarker in patients with diabetes and may be a better marker compared to other inflammatory reactants

ZINC AND B1-PROTEIN HIGH MOBILITY GROUPS IN CHILDREN WITH TYPE 1 MUMMARIES

Ciljevi: Cilj je ovog ispitivanja bio istražiti ulogu cinka i alarmina HMGB1 u razvitku šećerne bolesti tipa 1. Dokazana je uključenost proteina visoke mobilnosti iz skupine 1 (HMGB1) u raznim autoimunim i upalnim bolestima, međutim uloga ove proinflamatorne molekule kod djece sa šećernom bolesti tipa 1 (ŠBT1) nije do sada bila razjašnjena. Također je cilj bio usporediti razinu serumskog HMGB1 u djece u ranim fazama ŠBT1 (skupina 1) i onih s dužim trajanjem bolesti (skupina 2) s kontrolnom skupinom bez ŠBT1 ili drugih autoimunuh bolesti. Dizajn studije: Presječno ispitivanje Ispitanici: Ovo israživanje uključuje 141 dijete: skupina 1 (N = 28), skupina 2 (N = 73) i kontrolna skupina (N = 40). Materijali i metode: Mjerenja su uzeta iz seruma za sljedeće: HMGB1, cink, broj bijelih krvnih stanica, C-reaktivni protein, glukoza, hemoglobin A1C i β-stanična protutijela (GADA-65, IA-2, ICA). Rezultati: Djeca sa ŠBT1 imaju statistički značajno višu razinu serumskog HMGB1 (8,7 ug/L) u usporedbi s kontrolnom skupinom djece bez ŠBT1 (1,0 ug/L). Razina HMGB1 statistički je veća kod djece s dužim trajanjem bolesti (skupina 2: 8,7 ug/l, P < 0,001). Značajno nižu razinu cinka ima skupina djece sa ŠBT1 (10,7) u odnosu na kontrolnu skupinu (12,85). Usporedbom vrijednosti cinka s dužinom trajanja dijabetesa, značajno najnižu srednju vrijednost cinka (10,3 interkvartilnog raspona 9 – 11,7) imaju ispitanici kojima dijabetes traje duže od dvije godine. Zaključak: Viša razina HMGB1 u djece s ŠBT1 ukazuje na to da ova proinflamatorna molekula može poslužiti kao biomarker upale kod bolesnika s dijabetesom i može biti bolji marker u usporedbi s drugim reaktantima upale.Objectives: The aim of this study was to investigate the role of zinc and HMGB1 alarmin in the development of Type 1 diabetes. The involvement of the high-mobility group box 1 pro- tein (HMGB1) in various autoimmune and inflammatory diseases has been documented be- fore. However, the role of this proinflammatory molecule in children with diabetes type 1 (T1DM) has not been clarified so far. The aim of this study was to compare the level of serum HMGB1 in children within the early (Group 1) and late (Group 2) stages of T1DM, with the control group of children without T1DM or any other autoimmune disease. Study design: A cross-sectional study. Participants: The study included 141 children: Group 1 (N=28), Group 2 (N=73) and Con- trol group (N=40). Materials and Methods: The measurements were made on serum samples for: HMGB1, zinc, white blood cell count, C-reactive protein, glucose, haemoglobin A1C, and β-cells autoanti- bodies (GADA-65, IA-2, ICA). Results: The children with T1DM had a statistically significant higher serum levels of HMGB1 (experimental group: 8.7 µg/l) compared to the children without T1DM (control group: 1.0). The HMGB1 level was statistically higher in children with a longer disease dura- tion (Group 1: 4.9 µg/l; Group 2: 8.7 µg/l, P <0.001). The children with T1DM had signifi- cantly lower zinc levels (10.7) compared to the control group (12.85). Comparing the zinc values according to the duration of diabetes, the subjects with diabetes which lasts for more than two years have the significantly lowest mean zinc levels (10.3 of the interquartile range 9 – 11.7). Conclusion: The higher level of HMGB1 in children with T1DM indicates that this proin- flammatory molecule can serve as an inflammatory biomarker in patients with diabetes and may be a better marker compared to other inflammatory reactants

Serum Levels of the High-mobility Group box 1 Protein (HMGB1) in Children with Type 1 Diabetes Mellitus: Case-control Study

INTRODUCTION: The involvement of the high-mobility group box 1 protein (HMGB1) in various autoimmune and inflammatory diseases has been documented; however, the role of this proinflammatory molecule in children with diabetes type 1 (T1DM) has not been addressed. The aim of this case-control study is to compare the serum level of HMGB1 in children with newly diagnosed T1DM (group 1) and a control group composed of healthy children. MATERIAL AND METHODS: This case-control study included 136 children: group 1 (n = 96) and a control group (n = 40). Measurements were taken from serum for the following: HMGB1, white blood cell count, C-reactive protein, glucose, haemoglobin A1C, and β-cell autoantibodies (GADA-65, IA-2, ICA). HMGB1 was determined using enzyme-linked immunosorbent assay on a Labsystems iEMS Reader MF analyser (Labsystems Diagnostics Oy, Helsinki, Finland). RESULTS: The level (median and interquartile range) of HMGB1 was statistically higher (p < 0.001) in children with T1DM: 8.7 (5.0-9.8) µg/l, in comparison with the control group: 1.0 (0.6-1.4) µg/l. No correlation was found between HMGB1 and HbA1c in group 1, or between HMGB1 and BMI. A statistically higher percentage of positive children for autoantibodies were present in group 1 compared to the control group (p ≤ 0.001). HMGB1 serum levels were also tested and the presence of autoantibodies, and none of those antibodies correlated with the level of HMGB1. CONCLUSIONS: The higher level of HMGB1 in children with T1DM, compared to the control group, indicates that this proinflammatory molecule is a good candidate marker of inflammation in children with T1DM

Stężenia magnezu, cynku i żelaza w surowicy jako parametry mogące mieć istotne znaczenie w skutecznej kontroli cukrzycy typu 1 u dzieci

Wstęp. Pierwiastki śladowe przyczyniają się do rozwoju cukrzycy i jej powikłań w związku z ich rolą w metabolizmie glukozy i reakcji na stres oksydacyjny. Celem niniejszego badania było ustalenie różnicy w stężeniach magnezu, cynku i żelaza w surowicy między zdrowymi dziećmi a dziećmi z cukrzycą typu 1 (T1DM). Badanie to miało również na celu ustalenie, czy stężenia magnezu, cynku i żelaza w surowicy u dzieci z T1DM są skorelowane z czasem trwania choroby i jakością kontroli glikemii w tej grupie. Materiał i metody. W badaniu wzięło udział 99 dzieci chorych na T1DM i 40 dzieci zdrowych. Stężenia mag­nezu, cynku i żelaza w surowicy oceniono za pomocą metody fotometrycznej. Wyniki. W grupie dzieci z T1DM stężenia magnezu i cynku (p &lt; 0,001) były istotnie niższe niż w grupie kontrolnej, ale nie stwierdzono statystycznie istotnych różnic między grupami w stężeniach żelaza (p = 0,13). Mimo że stężenia badanych pierwiastków w surowicy nie różniły się istotnie w zależności od czasu trwania choroby, odkryto, że u dzieci z gorszą kontrolą glikemii stężenia cynku w surowicy były znacznie niższe (p &lt; 0,001), podczas gdy stężenia magnezu i żelaza pozostawały zbliżone (p = odpowiednio 0,07 i 0,21). Wnioski. W badaniu wykazano, że chociaż nie było istotnej różnicy w stężeniach żelaza w surowicy między dziećmi z T1DM a zdrową grupą kontrolną, u dzieci z T1DM stężenia magnezu i cynku w surowicy były istotnie niższe niż w grupie kontrolnej. Stężenia cynku w surowicy bezpośrednio korelowały również z gorszą kontrolą glikemii. Konieczne są dalsze badania w celu ustalenia, czy można wykorzystać suplementację magnezu i cynku lub ich spożycie w diecie do uzyskania lepszej kontroli glikemii u dzieci z T1DM

Severe Cranio-Cervical Stenosis in a Child with Saul-Wilson Syndrome: A Case Report

Introduction: Saul Wilson syndrome (SWS) is a rare congenital syndrome characterized by a variety of symptoms, mostly skeletal changes. Saul and Wilson were the first to describe children with extremely short stature and craniofacial dysmorphism. Case report: We present a case of a 15-years-old boy with clinical and radiological characteristics of SWS. Genetic examination identified a pathogenic heterozygous variant in the COG4 gene. Magnetic resonance imaging revealed a critical stenosis of the cranio-cervical junction (CCJ) which required surgical treatment to attempt sufficient neurological decompression. The patient underwent decompression of CCJ under general anesthesia. There was no significant radiological and clinical improvement during the postoperative period. Conclusions: SWS is presented as an extremely rare congenital disease in children. The clinical condition of our patient confined surgical possibilities, therefore further treatment in such patients should be appropriately evaluated

Severe Cranio-Cervical Stenosis in a Child with Saul-Wilson Syndrome: A Case Report

Introduction: Saul Wilson syndrome (SWS) is a rare congenital syndrome characterized by a variety of symptoms, mostly skeletal changes. Saul and Wilson were the first to describe children with extremely short stature and craniofacial dysmorphism. Case report: We present a case of a 15-years-old boy with clinical and radiological characteristics of SWS. Genetic examination identified a pathogenic heterozygous variant in the COG4 gene. Magnetic resonance imaging revealed a critical stenosis of the cranio-cervical junction (CCJ) which required surgical treatment to attempt sufficient neurological decompression. The patient underwent decompression of CCJ under general anesthesia. There was no significant radiological and clinical improvement during the postoperative period. Conclusions: SWS is presented as an extremely rare congenital disease in children. The clinical condition of our patient confined surgical possibilities, therefore further treatment in such patients should be appropriately evaluated

IL12RB2 Gene is Associated with the age of Type 1 Diabetes Onset in Croatian Family Trios

BACKGROUND: Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus. METHODS AND FINDINGS: We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation. CONCLUSIONS: Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset

Incidence of Type 1 Diabetes Mellitus in 0 to 14-yr-old Children in Croatia – 2004 to 2012 Study

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) among children and adolescents increased during the last 50 yr. The T1DM incidence in Croatia was 8.87/100.000/yr over 1995-2003, with an annual increase of 9%, which placed Croatia among countries with moderate risk for T1DM. AIM: To investigate incidence rates and trends of T1DM from 2004 to 2012 in 0 to 14-yr-old Croatian children, and to compare the results with previous studies in Croatia and other European countries. METHODS: T1DM crude incidence rates are estimated for the entire group and three subgroups: 0-4, 5-9, and 10-14 yr. Standardized incidence is calculated using the method of direct standardization according to World Health Organization (WHO) standard world population. The incidence rates by gender, age groups, seasonality, and calendar year, and their interactions were analyzed using Poisson regression model. RESULTS: A total of 1066 cases were ascertained over 2004-2012. The standardized incidence was 17.23/100.000/yr (95% CI: 16.19-18.26), with no significant differences in incidence rates or trends between boys and girls. Statistically significant annual increase of 5.87% (p < 0.001) was found for the whole group, and for the subgroups 5-9 yr (6.82%; p < 0.001) and 10-14 yr (7.47%; p < 0.001). In the youngest subgroup (0-4 yr), annual increase was lower (2.43%; p = 0338) and not statistically significant. CONCLUSION: The incidence of childhood T1DM is increasing in Croatia, thus placing Croatia among countries with high risk for T1DM. The annual increment of 5.87% is considerably lower than 9.0% reported earlier, but still higher than the European average (3.9%). The increase in incidence ceased in youngest children

Quantitative transmission disequilibrium analysis (Abecasis’s orthogonal test) in 262 family trios with age of T1DM onset as a quantitative variable.

*<p>Nominal p values are shown uncorrected for multiple testing. The Bonferroni-corrected significance threshold was p = 0.0125.</p>**<p>Empirical p-values were obtained using 10000 Monte Carlo permutations. Empirical significance threshold of 0.05 corresponded to a p-value of <0.0128.</p