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 analysis blood MeSH
- Adult MeSH
- Glucose analysis MeSH
- Glucose Tolerance Test methods MeSH
- Homeostasis drug effects physiology MeSH
- Insulin analysis blood MeSH
- Insulin Resistance physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Odds Ratio MeSH
- Needs Assessment MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic 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
- Adiposity MeSH
- Homeostasis MeSH
- Insulin Resistance * MeSH
- Middle Aged MeSH
- Humans MeSH
- Metabolic Syndrome blood MeSH
- Regression Analysis MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article 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
- Glucose MeSH
- Homeostasis MeSH
- Body Mass Index MeSH
- Insulin Resistance * MeSH
- Humans MeSH
- Prediabetic State * metabolism MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article 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.
- Publication type
- Journal Article 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
- Alanine Transaminase blood MeSH
- Alkaline Phosphatase blood MeSH
- Aspartate Aminotransferases blood MeSH
- Bilirubin blood MeSH
- Cytokines blood MeSH
- gamma-Glutamyltransferase blood MeSH
- Homeostasis * MeSH
- Hyperbilirubinemia blood etiology MeSH
- Hypoalbuminemia blood etiology MeSH
- Liver metabolism physiopathology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Liver Diseases blood etiology MeSH
- Intestinal Diseases therapy MeSH
- Parenteral Nutrition adverse effects MeSH
- Rats, Sprague-Dawley MeSH
- Triglycerides blood MeSH
- Bile Acids and Salts blood MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
CONTENTS -- ENVIRONMENTAL HEALTH CRITERIA FOR PRINCIPLES AND METHODS FOR THE ASSESSMENT OF RISK FROM INTAKE -- FOR AN ESSENTIAL TRACE ELEMENT 16 -- 3.1 Definition of an AROI . 16 -- hi -- EHC 228: Assessment 4.7.2 Selenium and iodine 31 -- 4.8 Genetically determined human variability and -- disorders of homeostasis 31 -- 4.9 Acquired disorders of homeostasis . 32 -- 5. APPLICATION OF HOMEOSTATIC MODEL IN -- HUMAN HEALTH RISK ASSESSMENT TO EXPOSURE TO ETEs . 40 -- 6.1 Summary
Environmental health criteria, ISSN 0250-863X 228
xviii, 60 s. : grafy ; 22 cm
- MeSH
- Safety MeSH
- Nutritional Physiological Phenomena MeSH
- Risk Assessment MeSH
- Homeostasis MeSH
- Nutritional Requirements MeSH
- Trace Elements MeSH
- Conspectus
- Veřejné zdraví a hygiena
- NML Fields
- veřejné zdravotnictví
- chemie, klinická chemie
- nutriční terapie, dietoterapie a výživa
- environmentální vědy
- biochemie
- NML Publication type
- publikace WHO
Auxin concentration gradients are informative for the transduction of many developmental cues, triggering downstream gene expression and other responses. The generation of auxin gradients depends significantly on cell-to-cell auxin transport, which is supported by the activities of auxin efflux and influx carriers. However, at the level of individual plant cell, the co-ordination of auxin efflux and influx largely remains uncharacterized. We addressed this issue by analyzing the contribution of canonical PIN-FORMED (PIN) proteins to the carrier-mediated auxin efflux in Nicotiana tabacum L., cv. Bright Yellow (BY-2) tobacco cells. We show here that a majority of canonical NtPINs are transcribed in cultured cells and in planta. Cloning of NtPIN genes and their inducible overexpression in tobacco cells uncovered high auxin efflux activity of NtPIN11, accompanied by auxin starvation symptoms. Auxin transport parameters after NtPIN11 overexpression were further assessed using radiolabelled auxin accumulation and mathematical modelling. Unexpectedly, these experiments showed notable stimulation of auxin influx, which was accompanied by enhanced transcript levels of genes for a specific auxin influx carrier and by decreased transcript levels of other genes for auxin efflux carriers. A similar transcriptional response was observed upon removal of auxin from the culture medium, which resulted in decreased auxin efflux. Overall, our results revealed an auxin transport-based homeostatic mechanism for the maintenance of endogenous auxin levels. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at http://osf.io/ka97b/.
- MeSH
- Biological Transport MeSH
- Cell Line MeSH
- Phylogeny MeSH
- Homeostasis MeSH
- Indoleacetic Acids metabolism MeSH
- Membrane Transport Proteins genetics metabolism MeSH
- Arabidopsis Proteins genetics metabolism MeSH
- Plant Growth Regulators metabolism MeSH
- Plant Proteins genetics metabolism MeSH
- Nicotiana genetics physiology MeSH
- Models, Theoretical MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
