Background and Objectives: The key pathogenetic mechanism of glucose metabolism disorders, insulin resistance (IR), can be assessed using the Homeostasis Model Assessment of IR (HOMA-IR). However, its application in clinical practice is limited due to the absence of cut-offs. In this study, we aimed to define the cut-offs for the Czech population. Methods: After undergoing anthropometric and biochemical studies, the sample of 3539 individuals was divided into either nondiabetics, including both subjects with normal glucose tolerance (NGT, n = 1947) and prediabetics (n = 1459), or diabetics (n = 133). The optimal HOMA-IR cut-offs between subgroups were determined to maximize the sum of the sensitivity and specificity for diagnosing type 2 diabetes mellitus (T2DM) or prediabetes. The predictive accuracy was illustrated using receiver operating characteristic (ROC) curves. Logistic regression was performed to assess the association between a target variable (presence/absence of T2DM) depending on the HOMA-IR score as well as on the age and sex. Results: The HOMA-IR cut-off between nondiabetics and diabetics for both sexes together was 3.63, with a sensitivity of 0.56 and a specificity of 0.86. The area under the ROC curve was 0.73 for T2DM diagnosing in both sexes. The HOMA-IR cut-off between the NGT subjects and prediabetics was 1.82, with a sensitivity of 0.60 and a specificity of 0.66. Logistic regression showed that increased HOMA-IR is a risk factor for the presence of T2DM (odds ratio (OR) 1.2, 95% confidence interval (CI) 1.14-1.28, p < 0.0001). The predictive ability of HOMA-IR in diagnosing T2DM is statistically significantly lower in females (OR 0.66, 95% CI 0.44-0.98). The results are valid for middle-aged European adults. Conclusions: The results suggest the existence of HOMA-IR cut-offs signaling established IR. Introduction of the instrument into common clinical practice, together with the known cut-offs, may contribute to preventing T2DM.

• MeSH
• cholesterol analýza   krev   MeSH
• dospělí MeSH
• glukosa analýza   MeSH
• glukózový toleranční test metody   MeSH
• homeostáza účinky léků   fyziologie   MeSH
• inzulin analýza   krev   MeSH
• inzulinová rezistence fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• odds ratio MeSH
• odhad potřeb MeSH
• průřezové studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43-0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31-0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003-0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

• Publikační typ
• časopisecké články MeSH

The aim of the study was to investigate whether routine clinical parameters, including visceral adiposity index (VAI) and atherogenic index of plasma (AIP), could become widely applicable predictors of insulin resistance (IR), evaluated using homeostasis model assessment (HOMA-IR, HOMA-ß), with regard to presence of metabolic syndrome (MS). The study comprised 188 individuals identified to meet the MS criteria during regular health examinations and an equal number of age, sex-matched controls without MS. The strongest correlations were noted between HOMA-IR and waist circumference (WC) in the MS group (r=0.57) as well as between HOMA-IR and alanine aminotransferase (ALT, r=0.57) or aspartate aminotransferase (r=0.56) in the controls, with a statistical significance of p<0.001. In a multivariate linear regression model, the predictors of HOMA-IR were WC (linear coefficient ß=0.1, p<0.001), ALT (ß=2.28, p<0.001) and systolic blood pressure (ß=0.04, p<0.001). HOMA-ß was determined by WC (ß=1.97, p=0.032) and ALT (ß=99.49, p=0.004) and inversely associated with age (ß=-1.31, p=0.004). Neither VAI nor AIP were significant predictors. The presence of MS was significantly associated with both HOMA-IR and HOMA-ß. These results indicate that WC and ALT appear to be reliable predictors of IR. Comprehensive assessment of these parameters may serve for estimating the level of IR.

• MeSH
• adipozita MeSH
• homeostáza MeSH
• inzulinová rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom krev   MeSH
• regresní analýza 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

INTRODUCTION: Insulin resistance (IR), a key pathogenesis mechanism of metabolic disorders, can be tested using homeostatic model assessment (HOMA). HOMA-IR quantifies peripheral tissue IR, whereas HOMA-β determines insulin secretion. The cross-sectional study aimed to examine non-linear associations of HOMA indices with age when adjusting for body mass index (BMI), and thus to investigate the indices' ability to reflect the real development of glucose metabolism disorders over time. MATERIAL AND METHODS: The sample comprised 3406 individuals without diabetes mellitus (DM) divided into those with normal glucose metabolism (NGT, n = 1947) and prediabetes (n = 1459) after undergoing biochemical analyses. Polynomial multiple multivariate regression was applied to objectify associations of HOMA with both age and BMI. RESULTS: Mean values of HOMA-IR and HOMA-β in individuals with NGT were 1.5 and 82.8, respectively, while in prediabetics they were 2.2 and 74.3, respectively. The regression proved an inverse non-linear dependence of pancreatic b dysfunction, expressed by HOMA-β, on age, but did not prove a dependence on age for HOMA-IR. Both indices were positively, statistically significantly related to BMI, with a unit increase in BMI representing an increase in HOMA-IR by 0.1 and in HOMA-β by 3.2. CONCLUSIONS: The mean values of HOMA indices showed that, compared with NGT, prediabetes is associated with more developed IR but lower insulin secretion. Both HOMA-IR and HOMA-b are predicted by BMI, but only HOMA-β is predicted by age. HOMA indices can reflect non-linear, closer-to-reality dependencies on age, which in many epidemiological studies are simplified to linear ones. The assessment of glucose metabolism using HOMA indices is beneficial for the primary prevention of IR and thus DM.

• MeSH
• glukosa MeSH
• homeostáza MeSH
• index tělesné hmotnosti MeSH
• inzulinová rezistence * MeSH
• lidé MeSH
• prediabetes * metabolismus   MeSH
• průřezové studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bezpečnost MeSH
• fyziologie výživy MeSH
• hodnocení rizik MeSH
• homeostáza MeSH
• nutriční nároky MeSH
• stopové prvky MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví
• chemie, klinická chemie
• nutriční terapie, dietoterapie a výživa
• environmentální vědy
• biochemie
• NLK Publikační typ
• publikace WHO

Low vitamin D status has been frequently associated with impaired glucose metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and several parameters of glucose homeostasis in virtually healthy subjects, and explored possible interaction with vitamin D receptor (VDR) polymorphism. Nondiabetic subjects without chronic medication or any known significant manifest disease were selected from large general-population based population survey. Insulin sensitivity and β cell secretion were calculated by homeostasis model assessment (HOMA) and soluble isoform of receptor for advanced glycation end-products (sRAGE) using commercial ELISA. Subjects were also genotyped for rs2228570 polymorphism of VDR. After adjustment for potential confounders, we observed a significant relationship between 25-OH-D and fasting glycemia (β coefficient=-5.904; p=0.002) or insulin sensitivity (β=0.042; p=0.001), but not with β cell secretion or sRAGE. We found also an interaction with VDR polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower insulin sensitivity than those with GG genotype plus highest 25-OH-D concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status was in virtually healthy subjects associated with decreased insulin sensitivity, namely in those with GG genotype of rs2228570 VDR polymorphism.

• MeSH
• dospělí MeSH
• glukosa metabolismus   MeSH
• homeostáza * MeSH
• inzulinová rezistence genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• průřezové studie MeSH
• receptory kalcitriolu genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• vitamin D analogy a deriváty   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biologické modely MeSH
• krysa rodu rattus MeSH
• mozek účinky léků   MeSH
• neurotoxiny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

BACKGROUND: The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. METHODS AND RESULTS: In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (P=0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L-1, 68-101 mg·dL-1) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L-1, 108-142 mg·dL-1; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P=0.002). CONCLUSIONS: Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dysfunkce pravé srdeční komory krev   diagnóza   patofyziologie   MeSH
• funkce pravé komory srdeční MeSH
• glukagon krev   MeSH
• glukózový toleranční test MeSH
• homeostáza MeSH
• inzulin krev   MeSH
• kachexie krev   diagnóza   patofyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• krevní glukóza metabolismus   MeSH
• Langerhansovy ostrůvky metabolismus   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční selhání krev   diagnóza   patofyziologie   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• centrální nervový systém MeSH
• degenerace nervu MeSH

BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. METHODS: Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. RESULTS: PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. CONCLUSIONS: This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This animal model serves as an experimental model to further investigate the pathogenesis of PNALD inflicted by steatosis and cholestasis.

• MeSH
• alanintransaminasa krev   MeSH
• alkalická fosfatasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• bilirubin krev   MeSH
• cytokiny krev   MeSH
• gama-glutamyltransferasa krev   MeSH
• homeostáza * MeSH
• hyperbilirubinemie krev   etiologie   MeSH
• hypoalbuminemie krev   etiologie   MeSH
• játra metabolismus   patofyziologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• nemoci jater krev   etiologie   MeSH
• nemoci střev terapie   MeSH
• parenterální výživa škodlivé účinky   MeSH
• potkani Sprague-Dawley MeSH
• triglyceridy krev   MeSH
• žlučové kyseliny a soli krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH