Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
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Projekt bude zaměřen na studium metabolických pochodů u pacientů s Alzheimerovou nemocí (AD) ve srovnání se změnami u zdravých seniorů. Z opakovaného vyšetření seniorů v 5-ti letém intervalu určíme, které změny námi sledovaných neuroaktivních biomarkerů doprovází přirozené stárnutí a které charakterizují patologické stárnutí. Cílem projektu bude zpřesnit prediktivní model pro identifikaci osob v riziku AD, zjednodušit a klinické praxi přiblížit dostupnost tohoto modelu. Náš přístup otevírá možnosti včasné farmakologické nebo preventivní intervence zacílené na konkrétní metabolickou dráhu. Význam plánovaného modelu spočívá v možnosti využít pro predikci onemocnění dostupnou tkáň - periferní krev. Projekt je naplánován jako pokračování předešlého projektu "Studium společných patogenetických faktorů Alzheimerovy choroby a diabetes mellitus 2. typu" (IGA MZČR NT13543-4). Projekt naváže na průběžné výsledky prokazující rozdíly v glukózové toleranci, v hladinách cirkulujících neuroaktivních steroidů a v hladinách některých cytokinů, adipokinů a inkretinů u AD oproti zdravým kontrolám.; The project will focus on metabolic processes in patients with Alzheimer’s disease (AD) compared to healthy seniors. Repeated examination of the subjects at 5-year interval should reveal which changes of the examined neuroactive biomarkers accompany natural aging, and which are associated with pathological aging. The aim of the study is to make a prediction model able to identify persons at risk of AD more precisely, to simplify the prediction model and make it applicable to clinical practice, thanks to detection of neuroactive biomarkers in peripheral blood. This approach opens the opportunity of early pharmacologic or preventive intervention focused on certain metabolic pathway. The project is proposed as continuation and completion of previous project “Study of Common Pathogenetic Factors in Alzheimer’s Disease and Type 2 Diabetes Mellitus” (IGA MZ ČR NT13543-4). It will build on the current results proving differences in glucose tolerance, concentrations of circulating neuroactive steroids, some cytokines, adipokines and incretins in AD compared to healthy subjects.
- Klíčová slova
- cytokiny, cytokines, inkretiny, adipokiny, incretins, adipokines, Alzheimerova nemoc, neurosteroidy, vícerozměrná regrese, Alzheimer's disease, neurosteroids, multidimensional regression,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
- MeSH
- hromadné sdělovací prostředky MeSH
- orální zdraví * MeSH
- vzdělávání pacientů jako téma MeSH
- Publikační typ
- rozhovory MeSH
Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.
In order to understand the pathological changes associated with glucose homeostasis in old age, it is necessary to know the natural changes in the processing of proinsulin to mature insulin. While there is abundant information about insulin production and function in diabetics, the situation in healthy adults and the elderly has surprisingly rarely been investigated. The aim of the study was to determine how proinsulin secretion changes in individuals with normal glucose tolerance during the process of natural aging. A total of 761 individuals (539 women, 222 men) aged 18-90 years with normal fasting glycemia (less than 5.6 mmol/l) were divided into five groups according to age. Body composition and levels of fasting blood glucose, proinsulin, insulin, and C-peptide were determined, and the ratios of proinsulin to both insulin and C-peptide were calculated. The homeostasis model of ?-cell function (HOMA F) and peripheral insulin resistance (HOMA R) were calculated. The effect of age was assessed using an ANOVA model consisting of the factors sex, age, and sex × age interaction. Statgraphics Centurion v. XVIII statistical software was used. Glycemia, insulin, C-peptide and HOMA R increased in both sexes up to 75 years. On the contrary, proinsulin levels as well as proinsulin/insulin and proinsulin/C-peptide ratios decreased with age up to 75 years. In normoglycemic and normotolerant people, both women and men, the aging process is associated with decreased insulin sensitivity compensated by potentiation of insulin production. In older age, there is also a gradual decrease in circulating proinsulin, which can be explained by its more efficient processing into active insulin by matured healthy beta cells.
- MeSH
- C-peptid MeSH
- dospělí MeSH
- inzulinová rezistence * fyziologie MeSH
- krevní glukóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- proinsulin * krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Adiponektin hraje důležitou roli v regulaci metabolismu glukózy a lipidů, zvyšuje citlivost na inzulin, potlačuje chronický zánět nízkého stupně, apoptózu, oxidační stres a aterosklerotické procesy. Nedávno však byly publikovány studie, které popisují spíše zvýšené hladiny cirkulujícího adiponektinu u pacientů s některými metabolickými, kardiovaskulárními a neurologickými onemocněními. Dokonce vysoké hladiny adiponektinu asociovaly s vyšší mírou úmrtnosti u těchto onemocnění. Situace, kdy se vyšší hladiny adiponektinu nepromítají do lepší inzulinové senzitivity, případně do dalších zdravotních přínosů, je označována jako „paradox adiponektinu“. Cílem tohoto článku je na základě nejnovějších poznatků ukázat možná vysvětlení tohoto jevu.
Adiponectin plays an important role in the regulation of glucose and lipid metabolism, increases insulin sensitivity, and suppresses low-grade chronic inflammation, apoptosis, oxidative stress, and atherosclerotic processes. However, studies have recently been published that describe rather elevated levels of circulating adiponectin in patients with some metabolic, cardiovascular, and neurological diseases. High levels of adiponectin were even associated with a higher mortality rate in these diseases. The situation in which higher levels of adiponectin do not translate into better insulin sensitivity or other health benefits is referred to as the „adiponectin paradox“. The aim of this article is to show possible explanations for this phenomenon based on the latest findings.
- MeSH
- adiponektin * agonisté farmakologie fyziologie škodlivé účinky MeSH
- inzulinová rezistence MeSH
- kardiovaskulární nemoci etiologie patofyziologie MeSH
- lidé MeSH
- metabolické nemoci etiologie patofyziologie MeSH
- neurodegenerativní nemoci etiologie patofyziologie MeSH
- rizikové faktory MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- Alzheimerova nemoc * etiologie patofyziologie MeSH
- lidé MeSH
- neurozánětlivé nemoci komplikace MeSH
- Check Tag
- lidé MeSH
Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer's disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine "breaking point" that leads to the pathogenesis of overt AD.
- MeSH
- adiponektin krev MeSH
- Alzheimerova nemoc krev patologie MeSH
- biologické markery krev MeSH
- komplement - faktor D analýza MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
