IGF-I/IGFBP-3 ratio: a mechanistic insight into the metabolic syndrome

2009 ◽  
Vol 116 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Justo Sierra-Johnson ◽  
Abel Romero-Corral ◽  
Virend K. Somers ◽  
Francisco Lopez-Jimenez ◽  
Anders Mälarstig ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Characteristic Curve ◽  
Model Assessment ◽  
Linear Regression Models ◽  
The Metabolic Syndrome ◽  
Igf I ◽  
Definition Of ◽  
Insight Into ◽  
Igfbp 3

Recent reports suggest that IGF (insulin-like growth factor)-I and IGFBP-3 (IGF-binding protein-3) have independent and opposing mechanistic effects on insulin. The aim of the present study was to assess the relationship between the IGF-I/IGFBP-3 ratio and the metabolic syndrome. We examined 3281 subjects (1463 men and 1818 women, aged 20–49 years), otherwise healthy adults, who participated in NHANES III (Third National Health and Nutrition Examination Survey), which has released measurements of IGF-I and IGFBP-3. Insulin resistance was estimated using the computer HOMA2 (homoeostatic model assessment 2) model. The updated ATP-III (Adult Treatment Panel III) definition of the metabolic syndrome was used. We applied adjusted logistic and linear regression models. After adjusting for age and race, men and women in the lowest quartile of the IGF-I/IGFBP-3 ratio were 3-fold more likely to meet the ATP-III definition of the metabolic syndrome and twice as likely to be insulin-resistant. Mean values of the IGF-I/IGFBP-3 ratio decreased significantly as the number of metabolic syndrome components increased (P<0.0001, as determined by ANOVA). The area under the ROC (receiver operating characteristic) curve for detecting insulin resistance using the IGF-I/IGFBP-3 ratio was 0.760, significantly improving upon either protein alone (P=0.01). In conclusion, the IGF-I/IGFBP-3 ratio is significantly associated with the metabolic syndrome. Calculating the ratio of these two proteins may provide insight into the metabolic syndrome clustering phenomenon.

scholarly journals Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study

2020 ◽  
Vol 36 (8) ◽  
Author(s):  
Maria de Fátima Haueisen Sander Diniz ◽  
Alline Maria Rezende Beleigoli ◽  
Maria Inês Schmidt ◽  
Bruce B. Duncan ◽  
Antônio Luiz P. Ribeiro ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Model Assessment ◽  
Adult Health ◽  
Homeostasis Model Assessment ◽  
The Metabolic Syndrome ◽  
Brazilian Cohort ◽  
Overweight Or Obesity

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

scholarly journals Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

2013 ◽  
Vol 98 (12) ◽  
pp. 4899-4907 ◽  
Author(s):  
Kyung Hee Park ◽  
Lesya Zaichenko ◽  
Mary Brinkoetter ◽  
Bindiya Thakkar ◽  
Ayse Sahin-Efe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Body Mass ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cvd Risk ◽  
Baseline Serum ◽  
The Metabolic Syndrome ◽  
Increased Risk

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P &lt; .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P &lt; .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension

Physiology ◽  
2007 ◽  
Vol 22 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Amy M. Jonk ◽  
Alfons J. H. M. Houben ◽  
Renate T. de Jongh ◽  
Erik H. Serné ◽  
Nicoloaas C. Schaper ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Microvascular Dysfunction ◽  
Important Risk Factor ◽  
Potential Mechanism ◽  
The Metabolic Syndrome ◽  
New Treatments ◽  
Insight Into

Obesity is an important risk factor for insulin resistance and hypertension and plays a central role in the metabolic syndrome. Insight into the pathophysiology of this syndrome may lead to new treatments. This paper has reviewed the evidence for an important role for the microcirculation as a possible link between obesity, insulin resistance and hypertension.

scholarly journals The Relationship between Epicardial Adipose Tissue Thickness and Serum Interleukin-17a Level in Patients with Isolated Metabolic Syndrome

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 97 ◽  
Author(s):  
Esra Demir ◽  
Nazmiye Harmankaya ◽  
İrem Kıraç Utku ◽  
Gönül Açıksarı ◽  
Turgut Uygun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Control Group ◽  
Model Assessment ◽  
Tissue Thickness ◽  
The Metabolic Syndrome ◽  
Epicardial Adipose Tissue Thickness ◽  
The Relationship

In this study, it was aimed to investigate the relationship between the epicardial adipose tissue thickness (EATT) and serum IL-17A level insulin resistance in metabolic syndrome patients. This study enrolled a total of 160 subjects, of whom 80 were consecutive patients who applied to our outpatient clinic and were diagnosed with metabolic syndrome, and the other 80 were consecutive patients who were part of the control group with similar age and demographics in whom the metabolic syndrome was excluded. The metabolic syndrome diagnosis was made according to International Diabetes Federation (IDF)-2005 criteria. EATT was measured with transthoracic echocardiography (TTE) in the subjects. IL-17A serum levels were determined using the ELISA method. Fasting blood glucose, HDL, triglyceride, and fasting insulin levels were significantly higher in the metabolic syndrome group compared to the control group. In addition, the metabolic syndrome group had significantly higher high-sensitivity C-reactive protein (hs-CRP) and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) levels than the control group. Similarly, serum IL-17A levels were significantly elevated in the metabolic syndrome group compared to the control group statistically (p < 0.001). As well, EATT was higher in the metabolic syndrome than the control group. Conclusion: By virtue of their proinflammatory properties, EATT and IL-17 may play an important role in the pathogenesis of the metabolic syndrome.

scholarly journals Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

2020 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Cornelia Then ◽  
Christina Gar ◽  
Barbara Thorand ◽  
Cornelia Huth ◽  
Holger Then ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Vascular Complications ◽  
Model Assessment ◽  
Incident Type ◽  
The Metabolic Syndrome ◽  
Incident Type 2 Diabetes

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

scholarly journals Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

2007 ◽  
Vol 51 (7) ◽  
pp. 1128-1133 ◽  
Author(s):  
Ivana Pivatto ◽  
Patricia Bustos ◽  
Hugo Amigo ◽  
Ana Maria Acosta ◽  
Antonio Arteaga
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Resistance Index ◽  
Cross Sectional Study ◽  
Blood Levels ◽  
Model Assessment ◽  
Cross Sectional ◽  
Predictive Values ◽  
The Metabolic Syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

scholarly journals The Metabolic Syndrome Is Associated with Reduced Central Serotonergic Responsivity in Healthy Community Volunteers

2006 ◽  
Vol 91 (2) ◽  
pp. 718-721 ◽  
Author(s):  
Matthew F. Muldoon ◽  
Rachel H. Mackey ◽  
Mary T. Korytkowski ◽  
Janine D. Flory ◽  
Bruce G. Pollock ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Serum Prolactin ◽  
Model Assessment ◽  
Serotonergic Activity ◽  
The Metabolic Syndrome ◽  
Community Volunteers ◽  
Healthy Community

Context: The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism. Objective: The objective of this study was to test the hypothesis that low central serotonergic activity is associated with the metabolic syndrome. Design, Setting, Participants: This was a cross-sectional study of 345 healthy community volunteers, aged 30–55 yr, not taking medications for hypertension, lipid disorders, or diabetes. Outcome Measures: Central serotonergic responsivity was assessed with the iv citalopram challenge test. The serum prolactin area under the curve (AUC) over 150 min was calculated, and all analyses were adjusted for age, sex, plasma citalopram concentration, and baseline prolactin. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Insulin resistance was estimated by homeostasis model assessment. Results: Compared with other individuals, persons meeting either NCEP or IDF criteria for the metabolic syndrome had lower mean prolactin responses (P &lt; 0.05 for both). Using logistic regression, a decrease in prolactin AUC of 1 sd (−13.6 ng/ml·h) more than doubled the odds of having the metabolic syndrome (NCEP criteria: odds ratio, 2.38; 95% confidence interval, 1.14–4.97; P = 0.02; IDF criteria: odds ratio, 2.80; 95% confidence interval, 1.48–5.30; P = 0.002). Finally, the prolactin AUC was negatively associated with insulin resistance (β = −0.03, P = 0.02). Conclusions: Corroborating previous evidence, the metabolic syndrome was associated with diminished brain serotonergic activity as reflected in a comparative blunting of the prolactin response to a selective serotonergic challenge. This association may have implications for the etiology, prevention, and treatment of the metabolic syndrome.

Effects of pharmacological reversal of hyperuricemia on features of the metabolic syndrome in patients with gouty arthritis

2018 ◽  
Vol 66 (7) ◽  
pp. 1031-1036
Author(s):  
Mariana Marin ◽  
Naim M Maalouf
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Gouty Arthritis ◽  
Oxidase Inhibitor ◽  
Model Assessment ◽  
Urine Ph ◽  
Serum Triglycerides ◽  
Xanthine Oxidase Inhibitor ◽  
The Metabolic Syndrome

Hyperuricemia has been associated in epidemiological studies with the development of obesity, hypertension, insulin resistance and type 2 diabetes. Nevertheless, it remains unclear whether lowering of serum uric acid (UA) alters any of the features of the metabolic syndrome. In this prospective study (ClinicalTrials.gov identifier: NCT01654276), 24 patients with gouty arthritis and hyperuricemia were treated for 6 months with the xanthine oxidase inhibitor febuxostat to lower serum UA to <6 mg/dL. Measurements of 24 hours ambulatory blood pressure (ABP) and serum and urine markers of the metabolic syndrome were measured at baseline and at the end of 6 months of febuxostat. The study population consisted of 18 men and 6 women, 18 of which completed the baseline and 6 months visits. Serum UA decreased significantly from 8.7±1.5 mg/dL at baseline to 4.4±1.1 mg/dL at 6 months (P<0.0001). During that time frame, there was no significant change in body mass index, systolic or diastolic blood pressure measured by 24 hours ABP monitor, serum glucose, insulin or homeostatic model assessment for insulin resistance, serum total and high-density lipoprotein-cholesterol, serum triglycerides or urine pH (P>0.05 for all). There was no correlation between parameters of the metabolic syndrome and the decline in serum UA or serum UA achieved at study end. In conclusion, in patients with gouty arthritis, UA lowering with febuxostat below 6 mg/dL had no significant impact on features of the metabolic syndrome.

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