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

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

Download Full-text

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

Acta Endocrinologica ◽

10.1530/eje-09-0058 ◽

2009 ◽

Vol 161 (2) ◽

pp. 223-230 ◽

Cited By ~ 15

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.

Download Full-text

Cut-off values of surrogate indices of insulin resistance as risk predictors for metabolic syndrome

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.813 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

P Pikó ◽

S z Fiatal ◽

Z s Kósa ◽

J Sándor ◽

R Ádány

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Roc Curve ◽

Youden Index ◽

Model Assessment ◽

Roc Curve Analysis ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Significant Difference ◽

Surrogate Measures

Abstract Background The metabolic syndrome (MS) based on insulin resistance (IR) is a cluster of conditions indicating an increased risk of cardiometabolic diseases. This study aimed to define valid cut-off values for surrogate measures for IR to predicting the risk for the development of MS in the Hungarian general (HG) and Roma (HR) populations. Methods This study included 397 HG and 368 HR subjects aged 20-64 years from a complex health survey in 2018/2019. Four surrogate measures, namely the homeostasis model assessment-IR (HOMA-IR), McAuley index (McA), TG to HDL-cholesterol ratio (TG/HDL-C) and TG and glucose index (TyG) were calculated for all participants. The cut-off values were determined as the value with the highest Youden index (YI) on the basis of results obtained by receiver operating characteristic (ROC) curve analysis for the development of MS on separate and combined populations. Results Since no significant difference could be detected between the results obtained on separate populations, cut-off values defined on the combined one are proposed to use for risk prediction. The area under the ROC curve was 0.753 (95%CI: 0.718-0.787) for HOMA-IR, 0.827 (95%CI: 0.797-0.856) for McA, 0.843 (95%CI: 0.814-0.872) for TG/HDL-C ratio and 0.862 (95%CI: 0.835-0.889) for TyG. The cut-off value was 2.32 (sensitivity (sens.) 70.9%; specificity (spec.) 69.0%; YI: 0.399) for HOMA-IR, 5.989 (sens. 69.7%; spec. 82.7%; YI: 0.524) for McA, 1.274 (sens. 73.4; spec. 84.3%; YI: 0.574) for TG/HDL-C ratio and 4.694 (sens. 77.2%; spec. 84.3%; YI: 0.615) for TyG. Concerning the fact, that the TyG has the best indicative power for predicting IR to the estimation of MS risk in both populations the IR/MS prevalence was defined by using TyG and found to be as high as 42.3% and 40.5% in the HG and HR populations, respectively. Conclusions Based on our results the TyG index could be a useful supplementary method for identifying individuals at risk for MS. Key messages The optimal cut-off points’ four surrogate indices of insulin resistance for the prediction of metabolic syndrome did not differ significantly between the Hungarian general and Roma populations. The triglyceride and glucose index proved to be the strongest predictor for the risk of metabolic syndrome in the Hungarian general and Roma populations.

Download Full-text

Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

Author(s):

Sezcan Mumusoglu ◽

Bulent Okan Yildiz

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Central Obesity ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Natural Menopause ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

Download Full-text

Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2373 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4899-4907 ◽

Cited By ~ 235

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 < .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 < .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.

Download Full-text

Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome

Food & Function ◽

10.1039/c6fo00339g ◽

2016 ◽

Vol 7 (8) ◽

pp. 3390-3401 ◽

Cited By ~ 13

Author(s):

Damiana D. Rosa ◽

Łukasz M. Grześkowiak ◽

Célia L. L. F. Ferreira ◽

Ana Carolina M. Fonseca ◽

Sandra A. Reis ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Animal Model ◽

Inflammatory Cytokine ◽

Fasting Glucose ◽

Cytokine Expression ◽

Fasting Insulin ◽

Insulin Levels ◽

Reduce Insulin Resistance

Kefir supplementation in rats with induced metabolic syndrome was able to lower fasting glucose, fasting insulin levels, and reduce insulin resistance.

Download Full-text

Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0371 ◽

2018 ◽

Vol 96 (1) ◽

pp. 97-102 ◽

Cited By ~ 1

Author(s):

Hanin Aburasayn ◽

Rami Al Batran ◽

Keshav Gopal ◽

Malak Almutairi ◽

Amina Eshreif ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Female Offspring ◽

Metabolic Dysfunction ◽

Insulin Resistant ◽

The Metabolic Syndrome ◽

Rate Versus ◽

Increased Risk ◽

Study Completion ◽

Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

Download Full-text

Abstract P437: Early Insulin Resistance Responds To Lifestyle Interventions: The Premier Study

Circulation ◽

10.1161/circ.141.suppl_1.p437 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

David P Cistola ◽

Jamy D Ard ◽

M. H Brenner ◽

Alok K Dwivedi

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Young Adults ◽

Controlled Trial ◽

Analysis Of Covariance ◽

Screening Tests ◽

Lifestyle Interventions ◽

Fasting Insulin ◽

Insulin Levels ◽

The Mean

Introduction: Compensatory hyperinsulinemia (CH) is the metabolic response to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintaining normal fasting glucose and lipid levels. Therefore, CH is undetected by conventional screening tests for diabetes and cardiovascular risk. Our prior work showed that CH is prevalent in the U.S., especially in teenagers, young adults and Hispanic populations. Moreover, CH in young adults doubles the risk for diabetes later in life, independent of other known risk factors. The current study tested the hypothesis that markers of early insulin resistance improve with behavioral lifestyle interventions. Methods: The parent PREMIER study was a randomized controlled trial to evaluate the effect of lifestyle interventions on blood pressure. Many subjects also had insulin resistance, prediabetes (PreD) and/or metabolic syndrome (MetS). The interventions included increased physical activity, weight loss, reduced sodium and alcohol intake, and the DASH diet (Dietary Approaches to Stop Hypertension). A total of 810 subjects were randomized into three intervention arms: “established”, “established plus DASH” and “advice only”. Established refers to the above interventions, except for DASH. The subjects were 62% women and 34% African Americans; the mean age was 50.0±8.9 years. Inclusion criteria were age ≥25, elevated BP and BMI of 18.5-45.0 kg/m 2 . Exclusion criteria were diabetes, history of cardiovascular event, heart failure, cancer or psychiatric hospitalization within the last 2 years. Here, the analysis of covariance method was used to determine whether markers of insulin resistance at 6 months improved in the established or established plus DASH arms compared with the advice-only arm, after adjusting for baseline values. The results are reported as geometric means and 95% confidence intervals (CI). Results: Subjects in the lifestyle intervention arms showed reduced fasting insulin and increased insulin sensitivity compared with the advice-only arm. The mean fasting insulin levels after 6 months of the established and established plus DASH interventions were 9.8 μIU/mL (95% CI: 9.3, 10.3) and 10.1 (9.6, 10.7), respectively, compared with 12.0 (11.4, 12.6) for advice only. After excluding subjects with PreD and/or MetS at baseline, insulin levels for established and established plus DASH were 8.0 (7.3, 8.7) and 8.3 (7.3, 9.0), respectively, as compared with 9.8 (9.1, 10.6) for advice only. Likewise, HOMA2 %S increased to 101.2 (92.5, 110.6) and 93.3 (85.6, 101.8), respectively, compared with 79.0 (73.0, 85.5) in the advice-only arm. Conclusion: Markers of insulin resistance improved with the PREMIER lifestyle interventions, even in subjects who did not meet the clinical criteria for prediabetes or metabolic syndrome. Early screening and intervention may improve diabetes prevention outcomes.

Download Full-text