scholarly journals Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

2009 ◽  
Vol 161 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Susanne R de Rooij ◽  
Jacqueline M Dekker ◽  
Michaela Kozakova ◽  
Asimina Mitrakou ◽  
Olle Melander ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Odds Ratio ◽  
Cardiometabolic Risk ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Men And Women ◽  
The Metabolic Syndrome ◽  
Preclinical Atherosclerosis

ObjectiveFasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.Design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.ResultsFasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.ConclusionsFasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.

scholarly journals Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

2013 ◽  
Vol 59 (6) ◽  
pp. 279-284
Author(s):  
Csép Katalin
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Fasting Insulin ◽  
Middle Aged ◽  
Insulin Levels ◽  
The Metabolic Syndrome ◽  
Sensitivity Indices ◽  
Increased Risk ◽  
Surrogate Measures

Abstract Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index) based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI), FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p <0.05). HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82). The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84). Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

scholarly journals High TSH Level within Normal Range Is Associated with Obesity, Dyslipidemia, Hypertension, Inflammation, Hypercoagulability, and the Metabolic Syndrome: A Novel Cardiometabolic Marker

2019 ◽  
Vol 8 (6) ◽  
pp. 817 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Shih-Che Hua ◽  
Chia-Hsuin Chang ◽  
Wei-Yi Kao ◽  
Hsiao-Lin Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Cardiometabolic Risk ◽  
Fasting Glucose ◽  
Reference Group ◽  
Elevated Blood ◽  
Normal Range ◽  
The Metabolic Syndrome

(1) Background: Overt and subclinical hypothyroidism has been associated with increased cardiometabolic risks. Here we further explore whether thyroid function within normal range is associated with cardiometabolic risk factors in a large population-based study. (2) Methods: We screened 24,765 adults participating in health examinations in Taiwan. Participants were grouped according to high-sensitive thyroid-stimulating hormone (hsTSH) level as: <50th percentile (0.47–1.48 mIU/L, the reference group), 50–60th percentile (1.49–1.68 mIU/L), 60–70th percentile (1.69–1.94 mIU/L), 70–80th percentile (1.95–2.3 mIU/L), 80–90th percentile (2.31–2.93 mIU/L), and >90th percentile (>2.93 mIU/L). Cardiometabolic traits of each percentile were compared with the reference group. (3) Results: Elevated hsTSH levels within normal range were dose-dependently associated with increased body mass index, body fat percentage, waist circumferences, blood pressure, hemoglobin A1c (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high homeostasis model of assessment of beta-cell (HOMA-β), triglycerides, total cholesterols, fibrinogen, and uric acids (p-for-trend <0.001), but not with fasting glucose levels. The association remained significant after adjustment of age, sex, and lifestyle. As compared to the reference group, subjects with the highest hsTSH percentile had significantly increased risk of being overweight (adjusted odds ratio (adjOR): 1.35), increased body fat (adjOR: 1.29), central obesity (adjOR: 1.36), elevated blood pressure (adjOR: 1.26), high HbA1c (adjOR: 1.20), hyperinsulinemia (adjOR: 1.75), increased HOMA-IR (adjOR: 1.45), increased HOMA-β (adjOR: 1.40), hypertriglyceridemia (adjOR: 1.60), hypercholesterolemia (adjOR: 1.25), elevated hsCRP (adjOR: 1.34), increased fibrinogen (adjOR: 1.45), hyperuricemia (adjOR: 1.47), and metabolic syndrome (adjOR: 1.42), but significant risk of low fasting glucose (adjOR: 0.89). Mediation analysis indicates that insulin resistance mediates the majority of the association between thyroid hormone status and the metabolic syndrome. (4) Conclusion: Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability.

scholarly journals Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P &lt; 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P &lt; 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

Analysis of candidate genes in Polish families with obesity

2004 ◽  
Vol 42 (5) ◽  
Author(s):  
Malgorzata Malczewska-Malec ◽  
Iwona Wybranska ◽  
Iwona Leszczynska-Golabek ◽  
Lukasz Partyka ◽  
Jadwiga Hartwich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
The Metabolic Syndrome

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

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.

scholarly journals Effect of the rs997509 Polymorphism on the Association between Ectonucleotide Pyrophosphatase Phosphodiesterase 1 and Metabolic Syndrome and Impaired Glucose Tolerance in Childhood Obesity

2009 ◽  
Vol 94 (1) ◽  
pp. 300-305 ◽  
Author(s):  
Nicola Santoro ◽  
Grazia Cirillo ◽  
Maria Grazia Lepore ◽  
Alfonsina Palma ◽  
Alessandra Amato ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Confidence Interval ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Odds Ratio ◽  
Rare Allele ◽  
Common Allele ◽  
Obese Children

Abstract Context: Variants on the nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1) gene have been associated with obesity and insulin resistance. Because insulin resistance is a pivotal factor in the development of metabolic syndrome (MS) and impaired glucose tolerance (IGT), we aimed to test the association between the K121Q and rs997509 ENPP-1 variants with obesity, MS and IGT in obese children and adolescents. Methods: We screened 809 children, 409 obese and 400 lean controls. Obese subjects underwent a standard oral glucose tolerance test, whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) were calculated. Results: No difference in prevalence for K121Q and rs997509 polymorphisms between obese and controls (P &gt; 0.05) were observed. Obese children carrying the rs997509 rare allele showed higher insulin (P = 0.001), HOMA (P &lt; .001) and lower WBISI values (P = 0.04) compared with common allele homozygous. A similar observation was done for K121Q variant, with 121Q allele carriers showing higher insulin (P = 0.03) and HOMA (P = 0.04) values than 121K homozygotes. Moreover, subjects carrying the rs997509 rare allele had higher risk of MS (odds ratio 2.4, 95% confidence interval: 1.3–4.3) and IGT (odds ratio 4.7, 95% confidence interval: 1.9–11.4) than common allele homozygotes. Evaluating combined effects of both polymorphisms, which are in strong linkage disequilibrium, we showed that the effect on insulin sensitivity was due to the rs997509 T variant. Conclusion: We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.

The effects of pioglitazone treatment on pancreatic cancer-related insulin resistance.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 329-329
Author(s):  
Jennifer Stern ◽  
Yull Edwin Arriaga ◽  
Arjun Gupta ◽  
Udit Verma ◽  
Sirisha Karri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pancreatic Cancer ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Post Treatment ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Fasting Insulin ◽  
Diabetes Status ◽  
Pioglitazone Treatment

329 Background: Insulin resistance (IR) in pancreatic cancer (PC) patients is associated with cachexia and poor outcome. Pioglitazone (PIO) improves insulin sensitivity via activation of peroxisome proliferator-activated receptor (PPAR gamma). Effects of PIO on insulin sensitivity, glucose homeostasis, and circulating adipokine levels in PC have not been examined. Methods: Patients with metastatic PC were administered PIO 45mg/day orally for 8 weeks concurrent with chemotherapy. Patients with known DM at enrollment were identified Fasting plasma was collected at baseline, weeks 2, 4, 6, 8 of pioglitazone treatment and at 2 weeks-post treatment. The primary objective was to describe changes in indicators of IR, including glucoregulatory hormone levels, glucose tolerance, and inflammatory cytokines. Results: Fourteen patients (age 64y), with a mean BMI of 28 were enrolled. Mean adiponectin increased from baseline to week 8 of treatment (14.2± 3.3 and 46.9±11.4µg/ml, respectively, P ≤ 0.01), and returned to baseline levels at 2 weeks post-treatment (15.1±1.9 µg/ml). Markers of IR (serum glucose, insulin, glucagon, and response to an oral glucose bolus) did not correlate with tumor size, inflammatory cytokine levels, GM-CSF, or CA19-9. A dichotomous response to PIO treatment was observed between non-diabetic and T2DM patients. Fasting insulin increased 70.6±31.3% from baseline to treatment week 8 in patients with T2DM. In contrast, treatment of non-diabetic patients decreased fasting insulin by 40.2±6.3%, demonstrating a significant, P ≤ 0.01, difference in treatment response between PC patients with or without T2DM. Conclusions: We have demonstrated that PC patients respond to 8 weeks of PIO treatment with a significant rise in the insulin sensitizing adipokine, Adiponectin, with a complete wash-out after 2 weeks of cessation. PIO results in opposing fasting insulin responses in non-diabetic and DM patients suggests that diabetes status plays a significant role in the glucoregulatory effects of PIO treatment in PC patients. Clinical trial information: NCT01838317.

scholarly journals Decreased insulin sensitivity in small for gestational age males treated with GH and preterm untreated males: a study in young adults.

2008 ◽  
Vol 158 (6) ◽  
pp. 899-904 ◽  
Author(s):  
J Rotteveel ◽  
M M van Weissenbruch ◽  
H A Delemarre-Van de Waal
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Gh Therapy ◽  
The Metabolic Syndrome ◽  
Preterm Born

BackgroundLow birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short.MethodsWe investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome.ResultsInsulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups.ConclusionInsulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.

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