The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
- MeSH
- autoprotilátky * MeSH
- ghrelin imunologie MeSH
- inzulin imunologie MeSH
- leptin imunologie MeSH
- lidé MeSH
- melanocyty stimulující hormony imunologie MeSH
- neuropeptid Y imunologie MeSH
- poruchy příjmu potravy imunologie mikrobiologie MeSH
- střevní mikroflóra imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Pozadie: Klasifikácia diabetu (DM) so vznikom v dospelom veku nie je vždy jednoduchá a u významnej časti pacientov, u ktorých bolo ochorenie iniciálne klasifikované a liečené ako diabetes mellitus 2. typu (DM2T) sa zisťujú znaky nasvedčujúce prítomnosti autoimunitnej inzulitídy (AI), ktorá je typická pre diabetes mellitus 1. typu (DM1T), resp. latentný autoimunitný diabetes dospelých (LADA). Cieľ: Zistiť, aký podiel pacientov vedených s DM2T má znaky AI, aký podiel z nich má súčasne nízku sekréciu inzulínu a aké klinické a laboratórne prejavy by sa dali využiť na odlíšenie týchto pacientov. Súbor a metódy: Randomizovaný klinický prieskum s vopred plánovaným rozsahom hodnotených parametrov u n = 625 pacientov, ktorí boli hospitalizovaní počas prvých 6 mesiacov roku 2016 v Národnom endokrinologickom a diabetologickom ústavu (NEDU) Ľubochňa. Okrem štandardných parametrov bol u každého pacienta vyšetrený C-peptid (CP) a autoprotilátky proti dekarboxyláze kyseliny glutámovej (GADA). Pacienti s pozitivitou GADA (GADA+) boli porovnávaní s pacientmi s GADA- v nasledovných parametroch: pohlavie, vek, vek v čase zistenia DM, trvanie DM, HbA1c, výskyt hypoglykémií, lipidogram, C-peptid nalačno, BMI, obvod pása, výskyt hypoglykémií, prítomnosť mikrovaskulárnych a makrovaskulárnych komplikácií, liečba diabetu a výskyt iných endokrinopatií. GADA+ s nízkym CP boli následne porovnávaní s GADA+ s normálnou hodnotou CP. Výsledky: Spomedzi 625 pacientov pôvodne klasifikovaných a liečených pre DM2T, 13 % bolo GADA+. Spomedzi nich malo 31 % nízke hodnoty CP (< 0,2 nmol/l) a 28 % hodnoty CP v intermediárnom pásme (0,2–0,4 nmol/l). Medzi GADA+ boli častejšie zastúpené ženy, mali nižší BMI, obvod pása, CP, vyšší HDL-cholesterol, častejší výskyt hypoglykémií a nižšiu celodennú dávku inzulínu. Pacienti s GADA+ a nízkym CP sa od GADA+ s normálnym CP líšili vyššími hodnotami HDL-cholesterolu, nižšími hodnotami triglyceridov a skoršou potrebou inzulínovej terapie. Vyšetrenie GADA a CP s ohľadom na ostatné relevantné charakteristiky viedlo k preklasifikovaniu resp. pridaniu diagnózy DM1T/LADA (ako hlavnej resp. súbežnej príčiny DM) u 2,9 % pacientov z celku a klinicky významný podiel AI bolo možné predpokladať v 6,1 % pacientov. Súhrn: Výsledky našej štúdie ukazujú, že v patogenéze DM u pacientov iniciálne diagnostikovaných a vedených ako DM2T a so súčasnou prítomnosťou GADA sa paralelne uplatňujú mechanizmy typické tak pre DM2T (inzulínová rezistencia) ako aj DM1T (autoimunitná inzulitída), a to v rôznej intenzite, rôznom pomere a v rôznej časovej následnosti, ako plynulé kontinuum, čo vysvetľuje aj rozdiely medzi jednotlivými pacientmi. Znakmi zdôrazňujúcimi podiel a úlohu AI sú podľa našich výsledkov vysoké titre GADA+, nízke hodnoty CP, skorá potreba liečby inzulínom, prítomnosť ochorení štítnej žľazy, vyššie hodnoty HDL–cholesterolu a nižšie hodnoty triglyceridov. Znakmi zdôrazňujúcimi dominanciu mechanizmov typických pre DM2T (inzulínová rezistencia) bola vyššia hodnota BMI, obvodu pása, normálna hodnota CP, nízka hodnota HDL-cholesterolu, vyššie hladiny triglyceridov, vyšší krvný tlak a hraničné titre GADA.
Background: It is not always easy to classify diabetes (DM) diagnosed in adults, with a significant group of patients initially classified and treated for type 2 diabetes mellitus (DM2T) presenting signs indicating the presence of autoimmune insulitis (AI), which is characteristic of type 1 diabetes mellitus (DM1T), or latent autoimmune diabetes mellitus in adults (LADA). Goal: Identify the proportion of patients entered with DM2T who present AI signs, and the number of patients of that proportion, who at the same time present low insulin secretion, and what clinical and laboratory manifestations could be used to differentiate between these patients. Cohort and methods: A randomized clinical trial with a pre-determined set of assessed parameters for n = 625 patients, who were hospitalized during the first 6 months of 2016 at the National Endocrinology and Diabetology Institute (NEDU), Lubochna. Apart from the standard parameters, C-peptide (CP) and autoantibodies to glutamic acid decarboxylase (GADA) were examined for each patient. GADA positive (GADA+) patients were compared to GADA negative (GADA-) patients in the following parameters: gender, age, age at the time of diagnosing DM, duration of DM, HbA1c, incidence of hypoglycemia, lipidogram, fasting C-peptide levels, BMI, waist circumference, incidence of hypoglycemias, presence of microvascular and macrovascular complications, treatment of diabetes and incidence of other endocrinopathies. GADA+ with low CP were subsequently compared to GADA+ patients with normal CP. Results: Of 625 patients originally classified and treated as DM2T, 13 % were GADA+. 31 % of them had low CP (< 0.2 nmol/l) and 28 % had CP levels within the intermediary range (0.2–0.4 nmol/l). Females made up a larger proportion of GADA+ patients, with a lower BMI, smaller waist circumference, lower CP, higher HDL cholesterol levels, a greater incidence of hypoglycemias and lower total daily dose of insulin. GADA+ patients with low CP differed from GADA+ patients with normal CP in higher HDL cholesterol levels, lower triglyceride levels and earlier need of insulin therapy. The testing for GADA and CP levels with regard to the other relevant characteristics led to re-classification, or more precisely adding of DM1T/LADA (as the main, or parallel cause of DM) for 2.9 % of all the patients included and a clinically significant proportion of AI could be assumed in 6.1 % of the patients. Summary: The results of our study show that the pathogenesis of DM in patients initially diagnosed and registered with DM2T and with concurrent presence of GADA includes mechanisms characteristic of both DM2T (insulin resistance) and DM1T (autoimmune insulitis) acting in parallel, with different intensity, in differing proportions and time sequence as a fluid continuum, which also accounts for the differences between individual patients. The characteristics highlighting the presence and role of AI based on our results include high titre of GADA+, low CP levels, early need of insulin therapy, presence of thyroid disorder, higher HDL cholesterol levels and lower triglyceride levels. The characteristics highlighting the dominance of mechanisms characteristic of DM2T (insulin resistance) included higher BMI and waist circumference values, normal CP levels, low HDL cholesterol levels, higher triglyceride levels, higher blood pressure and borderline titre of GADA.
- MeSH
- autoprotilátky * imunologie krev MeSH
- biologické markery krev MeSH
- C-peptid imunologie MeSH
- časové faktory MeSH
- cholesterol krev MeSH
- diabetes mellitus 1. typu * diagnóza farmakoterapie imunologie MeSH
- diabetes mellitus 2. typu * diagnóza farmakoterapie imunologie MeSH
- diabetes mellitus imunologie klasifikace MeSH
- dospělí MeSH
- glutamát dekarboxyláza imunologie MeSH
- glykovaný hemoglobin MeSH
- hypoglykemie MeSH
- index tělesné hmotnosti MeSH
- inzulin imunologie sekrece terapeutické užití MeSH
- komplikace diabetu MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nemoci štítné žlázy epidemiologie MeSH
- obvod pasu MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- randomizované kontrolované studie MeSH
The aim of this study was to describe the frequency and distribution of Saffold virus in longitudinal stool samples from children, and test for association with development of persistent autoantibodies predictive of type 1 diabetes. A cohort of Norwegian children carrying the HLA genotype associated with highest risk of type 1 diabetes ("DR4-DQ8/DR3-DQ2") was followed with monthly stool samples from 3 to 35 months of age. Blood samples were tested for autoantibodies to insulin, glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27 children with ≥ 2 repeatedly positive islet autoantibodies (cases), and 53 matched controls were analysed for Saffold virus genomic RNA by semi-quantitative real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6%) samples, with similar proportions between cases (2.5%) and controls (2.6%). The probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40). Viral quantities ranged from <1 to almost 105 copies/μl. Estimated odds ratio between islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95% CI: 0.57-6.91, p = 0.29). Saffold virus had no statistically significant association with islet autoimmunity.
- MeSH
- autoprotilátky krev MeSH
- Cardiovirus izolace a purifikace MeSH
- diabetes mellitus 1. typu krev genetika imunologie MeSH
- feces virologie MeSH
- glutamát dekarboxyláza imunologie MeSH
- HLA-DQ antigeny genetika MeSH
- infekce viry z rodu Cardiovirus krev imunologie virologie MeSH
- inzulin imunologie MeSH
- kojenec MeSH
- lidé MeSH
- longitudinální studie MeSH
- předškolní dítě MeSH
- tyrosinfosfatasy receptorového typu, třída 8 imunologie MeSH
- virová nálož MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Both the human leucocyte antigen (HLA) DRB1 and the HLA DQB1 gene loci play a role in the development and progression of autoimmune diabetes mellitus (T1DM). Similarly, the insulin promoter variable number tandem repeats (INS-VNTR) polymorphism is also involved in the pathogenesis of diabetes mellitus (DM). We studied the association between each of these polymorphisms and DM diagnosed in patients older than age 35 years. Furthermore, we analysed possible interactions between HLA DRB1/DQB1 and INS-VNTR polymorphisms. Based on C-peptide and GADA levels we were able to distinguish three types of diabetes: T1DM, latent autoimmune diabetes in adults (LADA) and T2DM. INS-VNTR was genotyped indirectly by typing INS-23HphI A/T polymorphism. The genotype and allele frequencies of INS-23HphI did not differ between each of the diabetic groups and group of healthy subjects. We did, however, observe an association between the INS-23HphI alleles, genotypes and C-peptide secretion in all diabetic patients: A allele frequency was 86.2% in the C-peptide-negative group vs. 65.4% in the C-peptide-positive group (P(corr.) < 0.005); AA genotype was found to be 72.4% in the C-peptide-negative group vs. 42.6% in the C-peptide-positive groups (P(corr.) < 0.01). The HLA genotyping revealed a significantly higher frequency of HLA DRB1*03 allele in both T1DM and LADA groups when compared to healthy subjects: T1DM (25.7%) vs. control group (10.15%), odds ratio (OR) = 3.06, P < 0.05; LADA (27.6%) vs. control (10.15%), OR = 3.37, P < 0.01. The simultaneous presence of both HLA DRB1*04 and INS-23HphI AA genotype was detected in 37.5% of the T1DM group compared to only 9.2% of the healthy individuals group (OR = 5.9, P(corr.) < 0.007). We summarize that in the Central Bohemian population of the Czech Republic, the INS-23HphI A allele appears to be associated with a decrease in pancreatic beta cell secretory activity. HLA genotyping points to at least a partial difference in mechanism, which leads to T1DM and LADA development as well as a more diverse genetic predisposition in juvenile- and adult-onset diabetes. The simultaneous effect of HLA and INS-VNTR alleles/genotypes predispose individuals to an increased risk of diabetes development.
- MeSH
- alely MeSH
- diabetes mellitus 1. typu genetika imunologie MeSH
- dospělí MeSH
- frekvence genu genetika imunologie MeSH
- genetická predispozice k nemoci MeSH
- HLA-DQ antigeny genetika imunologie MeSH
- HLA-DR antigeny genetika imunologie MeSH
- inzulin genetika imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- minisatelitní repetice genetika MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge.
- MeSH
- diabetes mellitus 1. typu diagnóza genetika MeSH
- finanční podpora výzkumu jako téma MeSH
- genetické nemoci vrozené diagnóza genetika MeSH
- HLA antigeny genetika imunologie izolace a purifikace MeSH
- inzulin genetika imunologie škodlivé účinky MeSH
- lidé MeSH
- receptory interleukinu-2 genetika imunologie MeSH
- regulační T-lymfocyty enzymologie fyziologie MeSH
- tyrosinfosfatasy genetika imunologie MeSH
- tyrosinkinasy genetika imunologie MeSH
- Check Tag
- lidé MeSH
V posledních letech dochází ke zvýšenému zájmu o výzkum vztahu diabetes mellitus k demenci či poklesu kognitivních funkcí. Z poměrně bohatých literárních zkušeností vyplývá, že diabetes mellitus sám o sobě způsobuje narušení kognitivních funkcí, a to bez ohledu faktoru věku či skutečnosti, zda se jedná o diabetes mellitus 1. nebo 2. typu. Diabetes mellitus 1. typu způsobuje zpomalení psychomotorického tempa, zatímco u diabetes mellitus 2. typu je spíše popisováno narušené ukládání nových informací. Přesný mechanizmus, jakým diabetes vede k narušení kognice, není však dosud dostatečně objasněn. V současnosti je však již známo několik hypotetických mechanizmů, které by mohly vysvětlovat vztah mezi diabetem a narušenou úrovní kognitivních funkcí. Další výzkum, zaměřený zejména na průběhové klinicko–zobrazovací či klinicko–patologické studie, je nezbytný k objasnění přesných etiopatogenetických mechanizmů stojících na pozadí vztahu diabetes mellitus a demence. Pro klinickou praxi je pak důležité si uvědomit, že prevence, včasná diagnostika a optimální léčba diabetu může vést ke snížení výskytu demence či narušení kognitivních funkcí.
An increased research interest in the relation between diabetes mellitus and dementia or deterioration of cognitive functions has been recently noticed. The relatively rich scientific literature in this topic shows that diabetes mellitus itself can cause an impairment of cognitive functions regardless patient's age or the fact whether he has type 1 or type 2 diabetes mellitus. Type 1 diabetes mellitus leads to a psychomotor retardation while type 2 diabetes mellitus tends to be associated with impaired storage of new information. The exact mechanism through which diabetes impairs cognition has not been explained sufficiently yet, but several hypothetical mechanisms which might explain the relation between diabetes and impaired cognition have been proposed. To explain the etiopathogenetic mechanisms underlying the relation between diabetes and dementia, further research, especially research focused on process clinical-imaging studies or clinical-pathological studies is necessary. As far as clinical practice is concerned, it is important to bear in mind that prevention, timely diagnosis and optimum treatment of diabetes may help to reduce incidence of dementia or cognitive functions' impairment.
- MeSH
- Alzheimerova nemoc etiologie komplikace patofyziologie MeSH
- diabetes mellitus diagnóza prevence a kontrola psychologie MeSH
- finanční podpora výzkumu jako téma MeSH
- inzulin genetika imunologie škodlivé účinky MeSH
- komplikace diabetu prevence a kontrola psychologie MeSH
- lidé MeSH
- neurokognitivní poruchy diagnóza epidemiologie prevence a kontrola MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- MeSH
- autoimunitní hepatitida imunologie komplikace krev MeSH
- autoprotilátky krev MeSH
- C-peptid krev MeSH
- diabetes mellitus 1. typu MeSH
- glukagon diagnostické užití MeSH
- inzulin imunologie sekrece MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- autoprotilátky krev MeSH
- diabetes mellitus 1. typu diagnóza genetika imunologie MeSH
- dítě MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DR antigeny genetika MeSH
- inzulin genetika imunologie MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- prediktivní hodnota testů MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Slovenská republika MeSH