scholarly journals The Insulin Sensitivity Mcauley Index (Mcai) is Associated with 40-Year Cancer Mortality in a Cohort of Men and Women Free of Diabetes at Baseline

2021 ◽  
Author(s):  
Yonatan Moshkovits ◽  
David Rott ◽  
Angela Chetrit ◽  
Rachel Dankner
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cancer Mortality ◽  
Model Assessment ◽  
Cancer Death ◽  
Men And Women ◽  
Adult Men ◽  
Sensitivity Indices ◽  
Increased Risk ◽  
Homeostatic Model Assessment

Abstract Background:The association between insulin resistance and cancer mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer mortality in a cohort of adult men and women free of diabetes. We hypothesized that higher insulin resistance (Q1 of the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, and Q4 of the Homeostatic Model Assessment (HOMA), calculated by fasting plasma glucose and insulin) will be associated with greater cancer mortality risk.Methods: A cohort of 1612 men and women free of diabetes during baseline were followed since 1979 through 2016 for cause specific mortality as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). Results: Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males, and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cumulative incidence analysis using Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status (table 2), revealed an increased risk for cancer death, sub-distribution HR=1.4 (95% CI: 1.1-1.9, p=0.02) for individuals in the lower quartile of MCAi (Q1), denoting higher insulin resistance, compared with the upper quartiles (Q2-4). No statistically significant association was observed between the other insulin resistance surrogates and cancer death.Conclusion: The MCAi was found to independently associate with an increased risk for cancer mortality in adult men and women free of diabetes. The MCAi may be considered as a long-term prognostic biomarker in diabetes-free adults.

scholarly journals Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

2021 ◽  
Author(s):  
Francesca Caroppo ◽  
Alfonso Galderisi ◽  
Laura Ventura ◽  
Anna Belloni Fortina
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Model Assessment ◽  
Limited Data ◽  
Single Center ◽  
Increased Risk ◽  
High Prevalence ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

AbstractPsoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.

scholarly journals The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

2011 ◽  
Vol 57 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Greisa Vila ◽  
Michaela Riedl ◽  
Christian Anderwald ◽  
Michael Resl ◽  
Ammon Handisurya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gastric Bypass ◽  
Insulin Sensitivity ◽  
Oral Glucose ◽  
Model Assessment ◽  
Obese Patients ◽  
Growth Differentiation Factor 15 ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model ◽  
The Relationship

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

scholarly journals PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiayu Huang ◽  
Lin Liu ◽  
Chunyan Chen ◽  
Ying Gao
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Predictive Biomarker ◽  
Normal Weight ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Model Assessment ◽  
Increased Risk ◽  
Homeostatic Model Assessment ◽  
Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

scholarly journals Depression and cardiovascular risk—association among Beck Depression Inventory, PCSK9 levels and insulin resistance

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
C. Macchi ◽  
C. Favero ◽  
A. Ceresa ◽  
L. Vigna ◽  
D. M. Conti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Risk Factor ◽  
Beck Depression Inventory ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Model Assessment ◽  
Cvd Risk ◽  
Assessment Index ◽  
Increased Risk ◽  
Homeostatic Model Assessment

Abstract Background Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. Results In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. Conclusions This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

scholarly journals The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 339
Author(s):  
Manuel A. González Hernández ◽  
Emanuel E. Canfora ◽  
Kenneth Pasmans ◽  
A. Astrup ◽  
W. H. M. Saris ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Positive Association ◽  
Fat Free Mass ◽  
Model Assessment ◽  
Random Factor ◽  
Before And After ◽  
Homeostatic Model Assessment ◽  
Matsuda Index

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (stdβ 0.130, p = 0.033) in women, but not in men (stdβ −0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals

2018 ◽  
Vol 66 (6) ◽  
pp. 1019-1022 ◽  
Author(s):  
Luis Rodrigo Cataldo ◽  
Rodrigo Fernández-Verdejo ◽  
José Luis Santos ◽  
Jose Eduardo Galgani
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
High Energy ◽  
12S Rrna ◽  
Model Assessment ◽  
Metabolic Homeostasis ◽  
Reading Frame ◽  
Homeostatic Model Assessment ◽  
Matsuda Index ◽  
Insight Into

Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that attenuates weight gain and hyperinsulinemia when administered to high fat-fed mice. MOTS-c is therefore a potential regulator of metabolic homeostasis under conditions of high-energy supply. However, the effect of insulin resistance and obesity on plasma MOTS-c concentration in humans is unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c concentration and analyzed its relationship with insulin sensitivity surrogates, in lean and obese humans (n=10 per group). Obese individuals had impaired insulin sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and obese individuals (0.48±0.16 and 0.52±0.15 ng/mL; p=0.60), it was correlated with HOMA (r=0.53; p<0.05) and Matsuda index (r=−0.46; p<0.05). Notably, when the groups were analyzed separately, the associations remained only in lean individuals. We conclude that plasma MOTS-c concentration is unaltered in human obesity. However, MOTS-c associates positively with insulin resistance mostly in lean individuals, indicating that plasma MOTS-c concentration depends on the metabolic status in this population. Such dependence seems altered when obesity settles. The implications of plasma MOTS-c for human metabolic homeostasis deserve future examination.

scholarly journals Genetic and Metabolite Variability in One-Carbon Metabolism Applied to an Insulin Resistance Model in Patients With Schizophrenia Receiving Atypical Antipsychotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Kristen M. Ward ◽  
Kyle Burghardt ◽  
A. Zarina Kraal ◽  
Andrew Jaeger ◽  
Larisa Yeomans ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Carbon Metabolism ◽  
Carrier Status ◽  
Diabetes Diagnosis ◽  
Model Assessment ◽  
Least Squares Regression ◽  
Increased Risk ◽  
Homeostatic Model Assessment ◽  
One Carbon Metabolism

Background: Patients with schizophrenia are at high risk of pre-mature mortality due to cardiovascular disease (CVD). Our group has completed studies in pharmacogenomics and metabolomics that have independently identified perturbations in one-carbon metabolism as associated with risk factors for CVD in this patient population. Therefore, this study aimed to use genetic and metabolomic data to determine the relationship between folate pharmacogenomics, one-carbon metabolites, and insulin resistance as measured using the homeostatic model assessment for insulin resistance (HOMA-IR) as a marker of CVD.Methods: Participants in this pilot analysis were on a stable atypical antipsychotic regimen for at least 6 months, with no diabetes diagnosis or use of antidiabetic medications. Participant samples were genotyped for MTHFR variants rs1801131 (MTHFR A1298C) and rs1801133 (MTHFR C677T). Serum metabolite concentrations were obtained with NMR. A least squares regression model was used to predict log(HOMA-IR) values based on the following independent variables: serum glutamate, glycine, betaine, serine, and threonine concentrations, and carrier status of the variant alleles for the selected genotypes.Results: A total of 67 participants were included, with a median age of 47 years old (IQR 42–52), 39% were female, and the median BMI was 30.3 (IQR 26.3–37.1). Overall, the model demonstrated an ability to predict log(HOMA-IR) values with an adjusted R2 of 0.44 and a p-value of &lt; 0.001. Glutamate, threonine, and carrier status of the MTHFR 1298 C or MTHFR 677 T allele were positively correlated with log(HOMA-IR), whereas glycine, serine, and betaine concentrations trended inversely with log(HOMA-IR). All factors included in this final model were considered as having a possible effect on predicting log(HOMA-IR) as measured with a p-value &lt; 0.1.Conclusions: Presence of pharmacogenomic variants that decrease the functional capacity of the MTHFR enzyme are associated with increased risk for cardiovascular disease, as measured in this instance by log(HOMA-IR). Furthermore, serine, glycine, and betaine concentrations trended inversely with HOMA-IR, suggesting that increased presence of methyl-donating groups is associated with lower measures of insulin resistance. Ultimately, these results will need to be replicated in a significantly larger population.

scholarly journals Significance and role of homeostatic model assessment in the evaluation of glucose regulation mechanisms

2017 ◽  
Vol 70 (5-6) ◽  
pp. 155-161
Author(s):  
Stanislava Nikolic ◽  
Nikola Curic ◽  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Damir Benc
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Glucose Regulation ◽  
Oral Glucose ◽  
Model Assessment ◽  
Oral Glucose Tolerance ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model

Introduction. Mathematical formulas, such as homeostatic model assessment indexes, proved to be useful for the estimation of insulin resistance. Nevertheless, numerous published results point to a considerable variability of their reference values. The aim of this study was to use homeostatic model assessment indexes and evaluate levels of insulin resistance in nondiabetic patients. Material and Methods. The study included 486 individuals (mean age 36.84 ? 12.86; 17% of males and 83% of females). Blood sampling was performed in order to determine glucose and insulin plasma levels, at the 0th and 120th minute of the oral glucose tolerance test. The indexes were calculated by the use of homeostatic model assessment 2 calculator, homeostatic model assessment of insulin resistance, homeostatic model assessment of insulin sensitivity, and homeostatic model assessment of ?-cells function. The results were statistically analyzed using a Data Analysis programme. Results. In the examined population, the average glycemic values of the oral glucose tolerance test were within the euglycemic scope (Gluc 0 = 4.76 ? 0.45 mmol/L; Gluc 120 = 5.24 ? 1.17 mmol/L), while the average values of calculated homeostatic model assessment indexes were: insulin resistance - 1.41 ? 0.82; ?-cells function - 131.54 ? 49.41%, and insulin sensitivity - 91.94 ? 47.32%. According to study cut-off values, homeostatic model assessment of insulin resistance was less than 2. We found 84 (17.28%) individuals with increased insulin resistance. Also, we set the lowest reference value for homeostatic model assessment of insulin sensitivity at less than 50%. With the probability of 66.67% (x? ? 1SD), basal insulin level under 11.9 mIU/L can be considered to correspond to physiologic level of insulin resistance. Conclusion. The follow-up of increased insulin resistance and altered secretion of pancreatic ?-cells, at early stages of glucose regulation disturbances, may be useful in assessing dynamics and level of glucose regulation disturbances and their appropriate treatment. <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/MPNS1708202E">10.2298/MPNS1708202E</a><u></b></font>

scholarly journals The biochemical assessment of insulin resistance

2007 ◽  
Vol 44 (4) ◽  
pp. 324-342 ◽  
Author(s):  
Anwar Borai ◽  
Callum Livingstone ◽  
Gordon A A Ferns
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Gold Standard Method ◽  
The Metabolic Syndrome ◽  
Increased Risk

Insulin resistance is a common condition, recognized to be a central feature of the metabolic syndrome, and strongly associated with an increased risk of cardiovascular disease and diabetes. The quantitative assessment of insulin sensitivity is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, aetiology and consequences. The gold standard method for the determination of insulin sensitivity is the euglycaemic hyperinsulinaemic clamp from which indices of insulin sensitivity can be derived. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. Indices can also be derived from measurements made during a standard oral glucose tolerance test and from one-off fasting specimens (e.g. homeostasis model assessment and quantitative insulin sensitivity check index). These indices lend themselves for use in large population studies where a relatively simple, inexpensive assessment is necessary. However, these tests all suffer from important limitations, including poor precision. Insulin resistance is increasingly being assessed in clinical situations, where relatively simple markers are required. Insulin-like growth factor binding protein-1 is an emerging marker which may be useful in this context.

scholarly journals Insulin sensitivity in critically ill patients: are women more insulin resistant?

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vincent Uyttendaele ◽  
J. Geoffrey Chase ◽  
Jennifer L. Knopp ◽  
Rebecca Gottlieb ◽  
Geoffrey M. Shaw ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Sex Differences ◽  
Insulin Sensitivity ◽  
Metabolic Response ◽  
Demographic Data ◽  
Randomised Trial ◽  
Preterm Neonates ◽  
Men And Women ◽  
Increased Risk ◽  
Significant Difference

Abstract Background Glycaemic control (GC) in intensive care unit is challenging due to significant inter- and intra-patient variability, leading to increased risk of hypoglycaemia. Recent work showed higher insulin resistance in female preterm neonates. This study aims to determine if there are differences in inter- and intra-patient metabolic variability between sexes in adults, to gain in insight into any differences in metabolic response to injury. Any significant difference would suggest GC and randomised trial design should consider sex differences to personalise care. Methods Insulin sensitivity (SI) levels and variability are identified from retrospective clinical data for men and women. Data are divided using 6-h blocks to capture metabolic evolution over time. In total, 91 male and 54 female patient GC episodes of minimum 24 h are analysed. Hypothesis testing is used to determine whether differences are significant (P < 0.05), and equivalence testing is used to assess whether these differences can be considered equivalent at a clinical level. Data are assessed for the raw cohort and in 100 Monte Carlo simulations analyses where the number of men and women are equal. Results Demographic data between females and males were all similar, including GC outcomes (safety from hypoglycaemia and high (> 50%) time in target band). Females had consistently significantly lower SI levels than males, and this difference was not clinically equivalent. However, metabolic variability between sexes was never significantly different and always clinically equivalent. Thus, inter-patient variability was significantly different between males and females, but intra-patient variability was equivalent. Conclusion Given equivalent intra-patient variability and significantly greater insulin resistance, females can receive the same benefit from safe, effective GC as males, but may require higher insulin doses to achieve the same glycaemia. Clinical trials should consider sex differences in protocol design and outcome analyses.

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