Pediatric Obesity

Debljina u djece i adolescenata postaje važan javnozdravstveni problem koji ugrožava njihovo zdravlje i duljinu života u odrasloj dobi. Nastaje kao rezultat kronične kalorijske neravnoteže u kojoj je svakodnevni kalorijski unos veći od potrošnje. Nasljedni faktori, okoliš, metabolizam, navike, kulturna obilježja i socioekonomski faktori imaju važnu ulogu u nastanku debljine. Endokrini uzroci debljine rijetki su i obično praćeni zaostajanjem u rastu. Genetički probir (skrining) rijetkih sindroma potreban je samo ako su prisutni specifični simptomi i znakovi koji upućuju na određeni sindrom. Komplikacije debljine započinju već u dječjoj dobi tako da je potrebno provoditi skrining za njihovo rano otkrivanje radi prevencije nastanka teških posljedica. Debljina utječe na kvalitetu života i psihosocijalno funkcioniranje osobe pa su psihološka procjena i savjetovanje djece i njihovih obitelji važan dio liječenja. Pristup liječenju debljine trebao bi biti multidisciplinaran te uključivati dijetu, fizičku aktivnost i bihevioralnu terapiju, a najučinkovitiji je ako su intervencije usmjerene prema cijeloj obitelji. Prevencija debljine u dječjoj dobi promjenom životnih navika djeteta i njegove obitelji, ali i težnja promjeni životnih navika populacije koje pogoduju debljanju ključne su pri sprječavanju epidemije debljine.Pediatric and adolescent obesity is becoming a serious public health concern and is threatening both the adult health and longevity. Obesity is a result of chronic caloric imbalance in which daily caloric intake is greater than its consumption. Genetic susceptibility, permissive environment, metabolic features, habits, and cultural and socioeconomic factors play a crucial role in the development of obesity. Endocrine etiologies of obesity are rare and usually accompanied by attenuated growth patterns. Genetic screening for rare syndromes is indicated only in the presence of specific historical or physical features. Obesity-related complications start in childhood, so screening for early identification should be carried out for the purpose of preventing serious consequences from ensuing. Obesity affects the quality of life and psychosocial development which makes individual and family screening for mental health issues, as well as counselling an indispensable part of prevention and treatment. Thus multidisciplinary approach to the treatment of childhood obesity should include diet, physical activity and behavioural therapy, and is most effective if the whole family is included. The prevention of pediatric obesity by promoting healthy diet and physical activity, as well as lifestyle modifications, should be essential in preventing the epidemic of obesity

Sindrom akutnog respiracijskog distresa u četvorogodišnjeg dječaka s dijabetičnom ketoacidozom - prikaz slučaja

Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management.Među poznatim inicijatorima sindroma akutnog respiracijskog distresa (ARDS) dijabetična ketoacidoza (DKA) je najrjeđi. U ovom radu prikazujemo 4-godišnjeg dječaka s DKA kao prvom manifestacijom o inzulinu ovisne šećerne bolesti u kojega se razvio ARDS te je zahtijevao mehaničku ventilaciju i preživio bez značajnijih posljedica. Kako bi se unaprijedilo preživljenje bolesnika s ARDS kao komplikacijom DKA liječnici trebaju biti upoznati s ovom rijetkom plućnom komplikacijom i njezinim pravilnim liječenjem

Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome

Abstract Wolcott-Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population. Conclusion: We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells

Are kidney malformations an additional feature of MEN2B syndrome? – Case report and literature review

Sindrom multiple endokrine neoplazije 2B (MEN2B) rijetka je autosomno dominatno nasljedna bolest uzrokovana mutacijama protoonkogena RET. Karakteriziran je pojavom medularnog karcinoma štitnjače već od rane, nerijetko dojenačke dobi, feokromocitoma koji je najčešće obostran, sluzničkim neuromima te drugim ekstraendokrinim manifestacijama i specifičnim fenotipskim značajkama koje mogu pomoći u prepoznavanju ovih bolesnika. Prikazujemo pacijenta sa sindromom MEN2B, dijabetesom melitusom tipa 1, inverznim položajem organa te prirođenim malformacijama bubrega i mokraćnog sustava. Pregledom literature uočeno je da se malformacije mokraćnog sustava opisuju i u drugih bolesnika sa sindromom MEN2B. Prepoznata uloga gena RET u razvoju anomalija mokraćnog sustava čini moguću etiološku poveznicu sa sindromom MEN2B. Predlažemo da se malformacije bubrega razmotre kao jedno od obilježja sindroma MEN2B. Budući da se osobine bolesnika sa sindromom MEN2B postupno razvijaju s dobi, prepoznavanje prirođene mane, uz prve znakove ostalih fenotipskih značajki, moglo bi pomoći ranom postavljanju dijagnoze i liječenju ovih bolesnika.Multiple endocrine neoplasia type 2B (MEN2B) is a rare familial syndrome caused by autosomal dominant mutations in the RET proto-oncogene. The disease is characterized by aggressive, early-onset medullary thyroid carcinoma, pheochromocytoma, most often bilateral, and mucosal neuromas together with other distinctive extra-endocrine manifestations and phenotypic features that can help in recognizing the patients and diagnosing the disease. We present the patient with MEN2B syndrome, type 1 diabetes mellitus, situs inversus and congenital kidney and urinary tract malformation. Reviewing the literature revealed other reports on urinary tract malformations in patients suffering from MEN2B. The recognized role of RET gene in kidney development and urinary tract malformations suggests a possible etiological link with MEN2B syndrome. We suggest that urinary tract malformations might be a feature of MEN2B syndrome. As most of the phenotype characteristics of the syndrome develop with age, recognizing congenital malformation might help in early diagnosing and treating the patients

Plasma fucosylated glycans and C-reactive protein as biomarkers of HNF1A-MODY in young adult–onset nonautoimmune diabetes

OBJECTIVE Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the commonest type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and hs-CRP are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes. RESEARCH DESIGN AND METHODS We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed. RESULTS We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L). CONCLUSIONS Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele

The association of HLA class II, CTLA-4 and PTPN22 genetic polymorphisms and autoantibodies to beta Langerhans islet cells in development of type I diabetes in patients with autoimmune thyroid disease

UVOD: Zajedniĉko pojavljivanje dijabetesa melitusa tip 1 (DMT1) i autoimune bolesti štitnjaĉe (AITD) u iste osobe klasificira se kao varijanta autoimunog poliglandularnog sindroma tip 3 (APS3v). Do sada su poznata najmanje 3 podloţna gena za nastanak APS3v i to geni HLA razreda II, gen CTLA-4 i gen PTPN22, a svi su ukljuĉeni u prezentaciju antigena T stanicama. ISPITANICI I METODE: U studiju je ukljuĉeno 323 nesrodnih bolesnika, 165 s DMT1 (94 s DMT1 bez AITD, 71 s APS3v), u dobi od 1.5-16.7 godina, i 158 s AITD (127 s autoimunim tiroiditisom, AT i 31 s Gravesovom bolešću, GB) u dobi od 4.3-25.9 godina. Kontrolna skupina ĉini 94 zdravih, nesrodnih ispitanika u dobi od 4.7-21.5 godina. Titrovi antitijela na citoplazmu β-stanice (ICA), glutamiĉku kiselu fosfatazu (GAD) i tirozin fosfatazu (IA-2), genotip HLA-DRB1, DQB1, polimorfizmi A49G i C60T gena CTLA4 te mutacija R620W gena PTPN22 ispitani su u svim skupinama ispitanika. RESULTATI: Uĉestalost autoimunosti na β-stanice Langerhansovih otoĉića u bolesnika s AITD bila je 10.76% (17/158), statistiĉki znaĉajno viša nego u kontrolnoj skupini ispitanika (0%, 0/94; p=0.001). Viša je uĉestalost naĊena u bolesnika s AT (11.81%, 15/127) nego s GB (6.45%, 2/31). Povišeni titrovi sva tri antitijela na β-stanice Langerhansovih otoĉića naĊeni su u 3 bolesnika s AITD, a troje je imalo pozitivna dva od ta tri antitijela. Svih šestero bolesnika razvilo je DMT1 tijekom razdoblja istraţivanja od 2 i pol godine. Nije naĊena statistiĉki znaĉajna razlika u uĉestalosti haplotipa HLA visokog i srednjeg rizika za razvoj DMT1 u bolesnika s AITD i pozitivnom β-staniĉnom autoimunosti u odnosu na kontrolnu skupinu ispitanika. Haplotipovi HLA niskog rizika za razvoj DMT1 statistiĉki su znaĉajno rjeĊe prisutni u bolesnika s AITD (31,3%) u odnosu na kontrolne ispitanike (69,9%; p=0,003). Riziĉni G/G genotip polimorfizma A49G gena CTLA4 statistiĉki je znaĉajno ĉešći u bolesnika s AITD i β-staniĉnom autoimunosti u odnosu na one bez (p=0.024). ZAKLJUČAK: Rezultati ove studije upućuju da su bolesnici s AITD, posebno s AT skloni razvoju β-staniĉne autoimunosti i DMT1, osobito oni u kojih su naĊeni povišeni titrovi više antitijela na β-stanice Langerhansovih otoĉića.BACKGROUND: Co-occurrence of type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) in the same patient is classified as variant of autoimmune polyglandular syndrome type 3 (APS3v). At least three susceptibility genes for this syndrome have been identified, HLA class II, CTLA-4 and PTPN22 gene, all involved in T-cells antigen presentation. SUBJECTS AND METHODS: The study comprised of 323 unrelated patients, 165 with T1D (94 with T1D alone, 71 with APS3v), aged 1.5-16.7 years, and 158 with AITD (127 with autoimmune thyroiditis, AT and 31 with Graves disease, GD), aged 4.3-25.9 years. The control group consisted of 94 unrelated healthy subjects, aged 4.7-21.5 years. Islet cell cytoplasmic (ICA), glutamic acid decarboxylase (GADA) and thyrosin phosphatase islet (IA-2) autoantibodies as well as HLA-DRB1, DQB1 genotypes, A49G and C60T polymorphisms of CTLA4 gene and R620W mutation of PTPN22 gene were analysed in all groups. RESULTS: The prevalence of β-cell autoimmunity in patients with AITD was 10.76% (17/158), significantly higher than in control subjects (0%, 0/94; p=0.001). Higher prevalence was found in patients with AT (11.81%, 15/127) than GD (6.45%, 2/31). All three β-cell autoantibodies were found in 3 patients, and three patients were positive to two autoantibodies. All six of them developed T1D during the investigation period of 2.5 years. No difference in frequency of high or moderate risk HLA haplotypes for development of T1D in patients with AITD and β-cell autoimmunity and control subjects was found. Low risk HLA haplotypes for development of T1D were found more frequently in control subjects than in patients with AITD and islet autoimmunity (69.9% vs 31.3%, p=0.003). Disease associated G/G genotype of CTLA4 gene A49G polymorphism was significantly more common in AITD patient with islet autoimmunity than in ones without (p=0.024). CONCLUSION: Our results indicate that patients with AITD, and in particular AT, are prone to develop β-cell autoimmunity and T1D, especially those with positive multiple islet cell autoantibodies

The association of HLA class II, CTLA-4 and PTPN22 genetic polymorphisms and autoantibodies to beta Langerhans islet cells in development of type I diabetes in patients with autoimmune thyroid disease

UVOD: Zajedniĉko pojavljivanje dijabetesa melitusa tip 1 (DMT1) i autoimune bolesti štitnjaĉe (AITD) u iste osobe klasificira se kao varijanta autoimunog poliglandularnog sindroma tip 3 (APS3v). Do sada su poznata najmanje 3 podloţna gena za nastanak APS3v i to geni HLA razreda II, gen CTLA-4 i gen PTPN22, a svi su ukljuĉeni u prezentaciju antigena T stanicama. ISPITANICI I METODE: U studiju je ukljuĉeno 323 nesrodnih bolesnika, 165 s DMT1 (94 s DMT1 bez AITD, 71 s APS3v), u dobi od 1.5-16.7 godina, i 158 s AITD (127 s autoimunim tiroiditisom, AT i 31 s Gravesovom bolešću, GB) u dobi od 4.3-25.9 godina. Kontrolna skupina ĉini 94 zdravih, nesrodnih ispitanika u dobi od 4.7-21.5 godina. Titrovi antitijela na citoplazmu β-stanice (ICA), glutamiĉku kiselu fosfatazu (GAD) i tirozin fosfatazu (IA-2), genotip HLA-DRB1, DQB1, polimorfizmi A49G i C60T gena CTLA4 te mutacija R620W gena PTPN22 ispitani su u svim skupinama ispitanika. RESULTATI: Uĉestalost autoimunosti na β-stanice Langerhansovih otoĉića u bolesnika s AITD bila je 10.76% (17/158), statistiĉki znaĉajno viša nego u kontrolnoj skupini ispitanika (0%, 0/94; p=0.001). Viša je uĉestalost naĊena u bolesnika s AT (11.81%, 15/127) nego s GB (6.45%, 2/31). Povišeni titrovi sva tri antitijela na β-stanice Langerhansovih otoĉića naĊeni su u 3 bolesnika s AITD, a troje je imalo pozitivna dva od ta tri antitijela. Svih šestero bolesnika razvilo je DMT1 tijekom razdoblja istraţivanja od 2 i pol godine. Nije naĊena statistiĉki znaĉajna razlika u uĉestalosti haplotipa HLA visokog i srednjeg rizika za razvoj DMT1 u bolesnika s AITD i pozitivnom β-staniĉnom autoimunosti u odnosu na kontrolnu skupinu ispitanika. Haplotipovi HLA niskog rizika za razvoj DMT1 statistiĉki su znaĉajno rjeĊe prisutni u bolesnika s AITD (31,3%) u odnosu na kontrolne ispitanike (69,9%; p=0,003). Riziĉni G/G genotip polimorfizma A49G gena CTLA4 statistiĉki je znaĉajno ĉešći u bolesnika s AITD i β-staniĉnom autoimunosti u odnosu na one bez (p=0.024). ZAKLJUČAK: Rezultati ove studije upućuju da su bolesnici s AITD, posebno s AT skloni razvoju β-staniĉne autoimunosti i DMT1, osobito oni u kojih su naĊeni povišeni titrovi više antitijela na β-stanice Langerhansovih otoĉića.BACKGROUND: Co-occurrence of type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) in the same patient is classified as variant of autoimmune polyglandular syndrome type 3 (APS3v). At least three susceptibility genes for this syndrome have been identified, HLA class II, CTLA-4 and PTPN22 gene, all involved in T-cells antigen presentation. SUBJECTS AND METHODS: The study comprised of 323 unrelated patients, 165 with T1D (94 with T1D alone, 71 with APS3v), aged 1.5-16.7 years, and 158 with AITD (127 with autoimmune thyroiditis, AT and 31 with Graves disease, GD), aged 4.3-25.9 years. The control group consisted of 94 unrelated healthy subjects, aged 4.7-21.5 years. Islet cell cytoplasmic (ICA), glutamic acid decarboxylase (GADA) and thyrosin phosphatase islet (IA-2) autoantibodies as well as HLA-DRB1, DQB1 genotypes, A49G and C60T polymorphisms of CTLA4 gene and R620W mutation of PTPN22 gene were analysed in all groups. RESULTS: The prevalence of β-cell autoimmunity in patients with AITD was 10.76% (17/158), significantly higher than in control subjects (0%, 0/94; p=0.001). Higher prevalence was found in patients with AT (11.81%, 15/127) than GD (6.45%, 2/31). All three β-cell autoantibodies were found in 3 patients, and three patients were positive to two autoantibodies. All six of them developed T1D during the investigation period of 2.5 years. No difference in frequency of high or moderate risk HLA haplotypes for development of T1D in patients with AITD and β-cell autoimmunity and control subjects was found. Low risk HLA haplotypes for development of T1D were found more frequently in control subjects than in patients with AITD and islet autoimmunity (69.9% vs 31.3%, p=0.003). Disease associated G/G genotype of CTLA4 gene A49G polymorphism was significantly more common in AITD patient with islet autoimmunity than in ones without (p=0.024). CONCLUSION: Our results indicate that patients with AITD, and in particular AT, are prone to develop β-cell autoimmunity and T1D, especially those with positive multiple islet cell autoantibodies

The association of HLA class II, CTLA-4 and PTPN22 genetic polymorphisms and autoantibodies to beta Langerhans islet cells in development of type I diabetes in patients with autoimmune thyroid disease

UVOD: Zajedniĉko pojavljivanje dijabetesa melitusa tip 1 (DMT1) i autoimune bolesti štitnjaĉe (AITD) u iste osobe klasificira se kao varijanta autoimunog poliglandularnog sindroma tip 3 (APS3v). Do sada su poznata najmanje 3 podloţna gena za nastanak APS3v i to geni HLA razreda II, gen CTLA-4 i gen PTPN22, a svi su ukljuĉeni u prezentaciju antigena T stanicama. ISPITANICI I METODE: U studiju je ukljuĉeno 323 nesrodnih bolesnika, 165 s DMT1 (94 s DMT1 bez AITD, 71 s APS3v), u dobi od 1.5-16.7 godina, i 158 s AITD (127 s autoimunim tiroiditisom, AT i 31 s Gravesovom bolešću, GB) u dobi od 4.3-25.9 godina. Kontrolna skupina ĉini 94 zdravih, nesrodnih ispitanika u dobi od 4.7-21.5 godina. Titrovi antitijela na citoplazmu β-stanice (ICA), glutamiĉku kiselu fosfatazu (GAD) i tirozin fosfatazu (IA-2), genotip HLA-DRB1, DQB1, polimorfizmi A49G i C60T gena CTLA4 te mutacija R620W gena PTPN22 ispitani su u svim skupinama ispitanika. RESULTATI: Uĉestalost autoimunosti na β-stanice Langerhansovih otoĉića u bolesnika s AITD bila je 10.76% (17/158), statistiĉki znaĉajno viša nego u kontrolnoj skupini ispitanika (0%, 0/94; p=0.001). Viša je uĉestalost naĊena u bolesnika s AT (11.81%, 15/127) nego s GB (6.45%, 2/31). Povišeni titrovi sva tri antitijela na β-stanice Langerhansovih otoĉića naĊeni su u 3 bolesnika s AITD, a troje je imalo pozitivna dva od ta tri antitijela. Svih šestero bolesnika razvilo je DMT1 tijekom razdoblja istraţivanja od 2 i pol godine. Nije naĊena statistiĉki znaĉajna razlika u uĉestalosti haplotipa HLA visokog i srednjeg rizika za razvoj DMT1 u bolesnika s AITD i pozitivnom β-staniĉnom autoimunosti u odnosu na kontrolnu skupinu ispitanika. Haplotipovi HLA niskog rizika za razvoj DMT1 statistiĉki su znaĉajno rjeĊe prisutni u bolesnika s AITD (31,3%) u odnosu na kontrolne ispitanike (69,9%; p=0,003). Riziĉni G/G genotip polimorfizma A49G gena CTLA4 statistiĉki je znaĉajno ĉešći u bolesnika s AITD i β-staniĉnom autoimunosti u odnosu na one bez (p=0.024). ZAKLJUČAK: Rezultati ove studije upućuju da su bolesnici s AITD, posebno s AT skloni razvoju β-staniĉne autoimunosti i DMT1, osobito oni u kojih su naĊeni povišeni titrovi više antitijela na β-stanice Langerhansovih otoĉića.BACKGROUND: Co-occurrence of type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) in the same patient is classified as variant of autoimmune polyglandular syndrome type 3 (APS3v). At least three susceptibility genes for this syndrome have been identified, HLA class II, CTLA-4 and PTPN22 gene, all involved in T-cells antigen presentation. SUBJECTS AND METHODS: The study comprised of 323 unrelated patients, 165 with T1D (94 with T1D alone, 71 with APS3v), aged 1.5-16.7 years, and 158 with AITD (127 with autoimmune thyroiditis, AT and 31 with Graves disease, GD), aged 4.3-25.9 years. The control group consisted of 94 unrelated healthy subjects, aged 4.7-21.5 years. Islet cell cytoplasmic (ICA), glutamic acid decarboxylase (GADA) and thyrosin phosphatase islet (IA-2) autoantibodies as well as HLA-DRB1, DQB1 genotypes, A49G and C60T polymorphisms of CTLA4 gene and R620W mutation of PTPN22 gene were analysed in all groups. RESULTS: The prevalence of β-cell autoimmunity in patients with AITD was 10.76% (17/158), significantly higher than in control subjects (0%, 0/94; p=0.001). Higher prevalence was found in patients with AT (11.81%, 15/127) than GD (6.45%, 2/31). All three β-cell autoantibodies were found in 3 patients, and three patients were positive to two autoantibodies. All six of them developed T1D during the investigation period of 2.5 years. No difference in frequency of high or moderate risk HLA haplotypes for development of T1D in patients with AITD and β-cell autoimmunity and control subjects was found. Low risk HLA haplotypes for development of T1D were found more frequently in control subjects than in patients with AITD and islet autoimmunity (69.9% vs 31.3%, p=0.003). Disease associated G/G genotype of CTLA4 gene A49G polymorphism was significantly more common in AITD patient with islet autoimmunity than in ones without (p=0.024). CONCLUSION: Our results indicate that patients with AITD, and in particular AT, are prone to develop β-cell autoimmunity and T1D, especially those with positive multiple islet cell autoantibodies

Povezanost biljega polimofizma gena HLA razreda II, CTLA-4 i PTPN22 te specifičnih autoantitijela protiv beta stanica Langerhansovih otočića s nastankom dijabetesa melitusa tipa 1 u bolesnika s autoimunom bolešću štitnjače [The association of HLA class II, CTLA-4 and PTPN22 genetic polymorphisms and autoantibodies to beta Langerhans islet cells in development of type I diabetes in patients with autoimmune thyroid disease]

BACKGROUND: Co-occurrence of type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) in the same patient is classified as variant of autoimmune polyglandular syndrome type 3 (APS3v). At least three susceptibility genes for this syndrome have been identified, HLA class II, CTLA-4 and PTPN22 gene, all involved in T-cells antigen presentation. SUBJECTS AND METHODS: The study comprised of 323 unrelated patients, 165 with T1D (94 with T1D alone, 71 with APS3v), aged 1.5-16.7 years, and 158 with AITD (127 with autoimmune thyroiditis, AT and 31 with Graves disease, GD), aged 4.3-25.9 years. The control group consisted of 94 unrelated healthy subjects, aged 4.7-21.5 years. Islet cell cytoplasmic (ICA), glutamic acid decarboxylase (GADA) and thyrosin phosphatase islet (IA-2) autoantibodies as well as HLA-DRB1, DQB1 genotypes, A49G and C60T polymorphisms of CTLA4 gene and R620W mutation of PTPN22 gene were analysed in all groups. RESULTS: The prevalence of β-cell autoimmunity in patients with AITD was 10.76% (17/158), significantly higher than in control subjects (0%, 0/94; p=0.001). Higher prevalence was found in patients with AT (11.81%, 15/127) than GD (6.45%, 2/31). All three β-cell autoantibodies were found in 3 patients, and three patients were positive to two autoantibodies. All six of them developed T1D during the investigation period of 2.5 years. No difference in frequency of high or moderate risk HLA haplotypes for development of T1D in patients with AITD and β-cell autoimmunity and control subjects was found. Low risk HLA haplotypes for development of T1D were found more frequently in control subjects than in patients with AITD and islet autoimmunity (69.9% vs 31.3%, p=0.003). Disease associated G/G genotype of CTLA4 gene A49G polymorphism was significantly more common in AITD patient with islet autoimmunity than in ones without (p=0.024). CONCLUSION: Our results indicate that patients with AITD, and in particular AT, are prone to develop β-cell autoimmunity and T1D, especially those with positive multiple islet cell autoantibodies

Acute Respiratory Distress Syndrome in a Four-Year-Old Boy with Diabetic Ketoacidosis – Case Report

Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management