Surrogate Of Insulin Resistance Research Articles

Triglyceride Glucose Index is an Independent Predictor for Cardiac Allograft Vasculopathy and Cardiovascular Mortality Following Heart Transplantation

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). The triglyceride glucose (TyG) index, the product of plasma glucose and triglycerides, a surrogate of insulin resistance, has been demonstrated to predict cardiovascular morbidity and mortality in the non-transplant population. We investigated the association between TyG index and cardiovascular outcomes following HT. <h3>Methods</h3> A total of 215 HT patients were assessed for TyG index using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Patients were divided into high and low TyG index groups according to the median value (8.91) at 3-month post HT. Endpoints included CAV, cardiovascular (CV) mortality, treated rejection (TR), and non-fatal major adverse cardiac events (NF-MACE). <h3>Results</h3> Baseline patient and donor clinical and demographic characteristics were similar for the two groups. Kaplan-Meier analyses showed that at 8 years after HT (median follow-up time), high TyG index was associated with lower freedom from CAV (69 vs. 87%, log-rank p = 0.003, Figure), lower freedom from the combined endpoint of CAV/CV mortality (64 vs. 82%, log-rank p=0.004), and lower freedom from NF-MACE (79 vs. 92%, log-rank p=0.009). There were no significant differences in freedom from TR. Multivariable analyses consistently demonstrated that a high TyG index was independently associated with a significant 3.2-fold increased risk of CAV and 2.40-fold increased risk of CAV/CV mortality (95%CI 1.51 to 6.88, p = 0.003, Figure; 95%CI 1.21 to 4.75, p = 0.02, respectively). <h3>Conclusion</h3> The study supports the strong association between the TyG index and HT outcomes. A high TyG index was an independent predictor of CAV and CV mortality. Further studies are needed to determine whether interventions for the TyG index have a positive impact on improving CAV outcomes.

Association between hypertension and insulin resistance in non-diabetic adult populations: a community-based study from the Iran

Background and objectives: High blood pressure increases the probability of insulin resistance and hyperinsulinemia. Also, insulin resistance can be defined as a risk factor for hypertension. The present study investigated the relationship between hypertension and insulin resistance in non-diabetic participants who were referred to Qazvin Metabolic Diseases Center. Material and methods: In this cross sectional study, 1103 participants (111 non-diabetic with newly diagnosed hypertension and 992 normotensive subjects aged ≥ 20 years) were enrolled from September 2014 to April 2016 in Qazvin (Iran). Systolic and diastolic blood pressure, insulin resistance, waist circumference, body mass index, triglycerides, cholesterol, LDL-cholesterol, fasting blood glucose (FBG) were measured. Fasting triglyceride to highdensity lipoprotein cholesterol ratio (TG/HDL-C) was used as a surrogate of insulin resistance. Data were analyzed using SPSS software and p < 0.05 was assumed as significant level. Results: Ten percent of all participants had hypertension. TG/HDL-C was 3.78 ± 3.28 in non-HTN and 5.76 ± 5.35 in HTN participants (p < 0.001). The frequency of all cardio-metabolic risk factors (except HDL cholesterol level) was higher in hypertensive group, after adjusting for age and gender (p < 0.001). Conclusion: Based on these results, essential hypertension is associated with a higher prevalence of hyperinsulinemia and insulin resistance in the non-diabetic community in Iran.

Association Between Triglyceride Glucose Index and Risk of New-Onset Diabetes Among Chinese Adults: Findings From the China Health and Retirement Longitudinal Study.

The triglyceride glucose (TyG) index has been proposed to be a surrogate of insulin resistance. In the present study, we aimed to examine the relationship between TyG index and the risk of incident diabetes in middle-age and older adults in China using nationally representative data from the China Health and Retirement Longitudinal Study 2011–2015. Information on socio-demographics, medical background, anthropometric measurement, and laboratory information were collected. The association between TyG index and diabetes was examined by Cox proportional hazards models and restricted cubic spline regression, and the results were presented in hazard ratio (HR) with 95% confidence interval (CI). Subgroup analyses were also conducted to examine potential interactions between demographics and TyG index. Among 7,428 participants, 791 (10.6%) of them developed diabetes over 3.4 years of follow-up. The multivariate HR for every SD increment in TyG index was 1.22 (95% CI, 1.14–1.31). When comparing to the lowest quartile of TyG index, the multivariate HRs for new-onset diabetes were 1.22 (0.96–1.54) for Q2, 1.61 (1.28–2.01) for Q3, and 1.73 (1.38–2.16) for Q4 (P for trend <0.001). The restricted cubic spline regression also showed a linear association. No interaction was found between subgroup variables and the association between TyG index and the risk of diabetes. In conclusion, higher TyG index associated with the elevated risk of new-onset diabetes in middle-aged and older adults.

Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1\xa0month accelerometer measurement

The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228.

The CNIC-polypill improves atherogenic dyslipidemia markers in patients at high risk or with cardiovascular disease: Results from a real-world setting in Mexico.

BackgroundIn many patients, the risk of cardiovascular (CV) events persists despite statin treatment and attaining target LDL–c levels. This residual risk is in part attributed to atherogenic dyslipidemia (AD). We studied the clinical effectiveness of the CNIC-polypill in improving the lipid profile, and lipid ratios and indices indicative of AD that are more accurate in predicting lipid-related CV risk.MethodsPost-hoc analysis of a multicenter, observational, non-comparative, prospective registry in 533 patients in Mexico. We evaluated blood lipids at baseline (usual care) and after 12 months of treatment with the CNIC-polypill (Sincronium®), including total cholesterol (TC), triglycerides (TG), cholesterol low-density lipoproteins (LDL–c), cholesterol high-density lipoproteins (HDL–c), and cholesterol non-high-density lipoproteins (non-HDL–c). We also calculated and compared AD-related lipid ratios and indices, including remnant cholesterol (RC), Castelli's risk index-I (CRI–I), atherogenic index (AI), atherogenic coefficient (AC), a surrogate of insulin resistance (IRS), atherogenic index of plasma (AIP), and lipoprotein combined index (LCI).ResultsAt 1 year of treatment, there was a significant reduction in the levels of TC (−22.6%), TG (−29.2%), LDL–c (−13.8%), and non-HDL–c (−29.2%) (all p < 0.001). The likelihood that patients attained their corresponding target LDL–c and TG levels was almost three-fold and seven-fold higher, respectively (p < 0.001). The values of the AD-related ratios RC, CRI–I, AI, AC, AIP, and LCI were all significantly lower (p < 0.001) after one year of treatment.ConclusionsIn patients with or at high risk of CVD, one-year treatment with the CNIC-polypill significantly lowered lipid ratios indicative of AD compared to baseline.

Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications.

Background:Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS).Methods:A cross-sectional study was performed including 326 participants with MetS (55–75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT (n = 254) and TyG (n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT.Results:Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [β = 3.07 (95% confidence interval (CI) 2.28−3.86; p trend < 0.001)], ALT [β = 7.43 (95% CI 2.23−12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [β = 14.12 (95% CI 3.64−24.61; p trend = 0.008)], FGF-21 [β = 190.69 (95% CI 93.13−288.25; p trend < 0.001)], FLI [β = 18.65 (95% CI 14.97−22.23; p trend < 0.001)] and HSI [β = 3.46 (95% CI, 2.23−4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62−0.79) compared with men (AUC = 0.570; 95% CI 0.48−0.66).Conclusions:A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.

Dietary Carbohydrates and Insulin Resistance in Adolescents from Marginalized Areas of Chiapas, México.

Evidence of the role that dietary carbohydrates (total carbohydrates, dietary fiber, total sugars, dietary glycemic index (GI) and glycemic load (GL)) exerts on insulin levels in adolescents is controversial. Thus, the aim of this study was to assess the association between dietary carbohydrates and insulin resistance in adolescents from Chiapas, México. A cross-sectional study was conducted in 217 adolescents. Sociodemographic, anthropometric, dietary and biochemical data were obtained. Total carbohydrates, dietary fiber, total sugars, dietary GI and GL were calculated from 24 h recalls. Two validated cut-off points for the homeostasis model assessment of insulin resistance (HOMA-IR) were used as surrogates of insulin resistance. Fasting insulin levels ≥ 14.38 μU/mL were considered as abnormal. Multivariate logistic regression models were fitted to assess the association between tertiles of dietary carbohydrates and insulin resistance or hyperinsulinemia. In our study, adolescents with the highest dietary fiber intake had lower odds of HOMA-IR > 2.97 (OR = 0.34; 95% CI: 0.13–0.93) when adjusted for sex, age, body fat percentage and saturated fatty acids intake. No significant associations were found for the rest of the carbohydrate variables. In summary, high-fiber diets reduce the probability of insulin resistance in adolescents from marginalized areas of Chiapas, México.

Low birth weight, a risk factor for diseases in later life, is a surrogate of insulin resistance at birth.

: Low birth weight (LBW) is associated with diseases in adulthood. The birthweight attributed risk is independent of confounding such as gestational age, sex of the newborn but also social factors. The birthweight attributed risk for diseases in later life holds for the whole spectrum of birthweight. This raises the question what pathophysiological principle is actually behind the association. In this review, we provide evidence that LBW is a surrogate of insulin resistance. Insulin resistance has been identified as a key factor leading to type 2 diabetes, cardiovascular disease as well as kidney diseases. We first provide evidence linking LBW to insulin resistance during intrauterine life. This might be caused by both genetic (genetic variations of genes controlling glucose homeostasis) and/or environmental factors (due to alterations of macronutrition and micronutrition of the mother during pregnancy, but also effects of paternal nutrition prior to conception) leading via epigenetic modifications to early life insulin resistance and alterations of intrauterine growth, as insulin is a growth factor in early life. LBW is rather a surrogate of insulin resistance in early life - either due to inborn genetic or environmental reasons - rather than a player on its own.

Comparison of various steady state surrogate insulin resistance indices in diagnosing metabolic syndrome

BackgroundInsulin resistance is core cause of metabolic syndrome. Determining insulin resistance is one of the foremost requirements imperative to understanding the pathophysiology of disease. The gold standard “Euglycaemic clamp test” is cumbersome, long and non-feasible in routine clinical setups to diagnose metabolic syndrome. Various continuous and steady state insulin resistance indices are now available in literature. We plan to evaluate commonly utilized steady state insulin resistance indices directly and Homeostasis Model Assessment for Insulin Resistance (HOMAIR) with added triglyceride (HOMA-TG index).MethodsThe cross-sectional study was carried from Jan-2016 to Dec-2018 at PNS HAFEEZ and department of chemical pathology, AFIP with following objectives: (1) To evaluate steady state insulin resistance markers for diagnosing metabolic syndrome as per IDF defined criteria by ROC curve analysis, (2) to measure Kendal Concordance between various insulin resistance indices and (3) to correlate steady state insulin resistance markers with anthropometric and lipid indices. After several exclusions we selected 224 subjects based upon “non-probability convenience sampling” for inclusion in study. Clinical history, anthropometric measures were calculated and sampling was done for insulin, glucose and other biochemical parameters. Metabolic syndrome was diagnosed as per IDF criteria, while HbA1c was utilized to diagnose diabetes mellitus. Pearson correlation was used to correlate various steady state insulin resistance indices including HOMAIR, HOMA2 index, QUICKI, G/I ratio, HOMA-TG index and serum insulin. AUC was calculated by ROC analysis for all surrogate insulin measures in diagnosis of metabolic syndrome.Results“HOMA-TG index” has shown the highest AUC for diagnosing metabolic syndrome along with higher correlation with lipid markers and anthropometric indices in comparison to other steady-state insulin resistance markers. Furthermore, QUICKI and G/I ratio showed the lowest AUC for detection of metabolic syndrome.Conclusion“HOMA-TG index” has shown highest AUC for metabolic syndrome diagnosis. However, QUICKI and G/I ration showed the lowest AUC for detection of metabolic syndrome. It is hoped that the potential “HOMA-TG index” may provide better diagnostic efficiency for diagnosing metabolic syndrome.

The Association Between Six Surrogate Insulin Resistance Indexes and Hypertension: A Population-Based Study.

Background: The relationship between insulin resistance and hypertension is well established, but the association of different surrogate insulin resistance indexes with the presence of hypertension is still under debate. The aim of this study was to compare the strength of the association between the presence of hypertension and six indexes: triglyceride/HDL cholesterol ratio (TG/HDL-C), Triglyceride Glucose (TyG) Index, Visceral adiposity index (VAI), Lipid accumulation product (LAP), TyG-Body mass index (TyG-BMI), and TyG-Waist circumference (TyG-WC). Methods: Data from a cross-sectional epidemiological study enrolling a sample representative for the Romanian population aged 18-80 years, excluding those with diabetes or requiring treatment for hypertriglyceridemia, were used to calculate the six indexes. The association with the presence of hypertension was examined with binomial and multinomial logistic regression. Results: In multinomial logistic models, which included age, gender, smoking, drinking, sedentary lifestyle, estimated glomerular filtration rate, urinary sodium, urinary albumin creatinine ratio, and use of medications known to influence insulin resistance as covariates, all individual components and surrogate insulin resistance indexes were independently associated with the presence of hypertension. Values of pseudo R square ranged from 0.342 for the multivariate model including TG/HDL-C to 0.357 for the model including TyG-WC, but with no clear superiority of any of the tested indexes over all others. Models including BMI and WC had a similar ability to predict the presence of hypertension as most of the surrogate indexes and they were slightly superior to TG/HDL-C and TyG. Conclusions: Although TG/HDL-C, VAI, LAP, TyG, TyG-BMI, and TyG-WC were independently associated with the presence of hypertension, no superiority could be demonstrated over the use of BMI and WC as predictors of hypertension in this cross-sectional study.

Estimate of reduced glomerular filtration rate by triglyceride-glucose index: insights from a general Chinese population

ABSTRACTObjectives: Recent studies have identified triglyceride-glucose index (TyG) as a surrogate of insulin resistance. Since insulin resistance correlates with renal damage, our study aims to investigate the impact of TyG on the risk of reduced eGFR and explore its value to improve the risk stratification and prevention of reduced eGFR.Methods: This cross-sectional study included 6466 participants (mean age:59.57 years, 60.2% females) from rural areas of northeast China between September 2017 to May 2018. TyG was calculated as ln[fasting triglyceride (mg/dL)×fasting plasma glucose (mg/dL)/2]. Reduced eGFR was defined as eGFR<60ml/min per 1.73m2.Results: The prevalence of reduced eGFR was 2.94%. After full adjustment, each SD increase of TyG caused 42.6% additional risk for reduced eGFR. When dividing TyG into quartiles, the top quartile had a 1.934 times risk than the bottom quartile. Furthermore, the risk of reduced eGFR increased linearly with the increment of TyG. Subgroup analysis also revealed the association was robust to several risk factors of renal damage. Finally, category-free net reclassification index (0.204, 95% CI: 0.060–0.349, p = 0.005) and integrated discrimination index (0.010, 95% CI: 0.005–0.016, p < 0.001) demonstrated the value of TyG to refine the risk stratification of reduced eGFR.Conclusion: Our work reveals the robust association between TyG and reduced eGFR. Moreover, the present study implicates the potential role of TyG as a risk indicator to optimize the prevention of reduced eGFR. Lastly, the findings also suggest the importance of simultaneous glycemic and lipid control to avoid the development and progression of reduced eGFR.

Usefulness of the Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C) in prediction of metabolic syndrome in Polish obese children and adolescents.

The triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) is a useful surrogate marker of insulin resistance and cardiovascular risk factors. We aimed to assess the relationship between the TG/HDL-C ratio and insulin resistance (IR) and its usefulness in prediction of the metabolic syndrome (MS). This retrospective study involved 122 obese children with the mean age of 11.6±3 years and their 58 healthy lean peers. Anthropometric measurements, blood pressure, the plasma lipid profile and oral glucose tolerance test (OGTT) were analyzed. Based on the obtained results, the TG/HDL-C ratio and surrogate insulin resistance indices (HOMA-IR, FGIR, QUICKI, OGIS, Matsuda index) were calculated. The TG/HDL-C ratio positively correlated with weight, waist circumference, waist to hip ratio (WHR), lipid profile, HOMA-IR, fasting insulin and insulin measurements during OGTT, and negatively correlated with FGIR, QUICKI, OGIS, and the Matsuda index. Obese children with the TG/HDL-C ratio≥3 (47.5%) had higher values of WHR and HOMA-IR, and lower ones of FGIR, QUICKI, OGIS, and the Matsuda index when compared to their obese peers with the TG/HDL-C<3. The area under the curve (AUC) calculated for each insulin resistance index in prediction of the metabolic syndrome was the largest for the TG/HDL-C ratio (0.8936, 95% Cl:0.809-0.977, p=0.000). For 1 unit increase in the TG/HDL-C ratio, the odds for having MS increased by 2.09 times. The TG/HDL-C ratio is a good surrogate marker of insulin resistance in obese children. When comparing the usefulness of some IR markers in prediction of the metabolic syndrome, the TG/HDL-C ratio seems to be the best one and should be used in clinical practice to identify children at risk of metabolic syndrome development.

Optimal Cut-off Points of Fasting and Post-Glucose Stimulus Surrogates of Insulin Resistance as Predictors of Metabolic Syndrome in Adolescents According to Several Definitions

Objective:The aim of this study was to determine optimal cut-off points for fasting and post-glucose stimulus surrogates of insulin resistance to predict metabolic syndrome in adolescents according to several definitions.Methods:One hundred fifty-five adolescents living in Mexico City were enrolled during 2011 and 2012. Waist circumference and blood pressure were recorded. Subjects received an oral glucose load of 1.75 g per kg up to a maximum dose of 75 g. Blood samples were drawn at baseline and 120 minutes. Concentrations of plasma glucose, triglycerides, high-density lipoprotein cholesterol and insulin were determined.Results:The frequency of metabolic syndrome showed a large variability when using a variety of published definitions; in contrast, the optimal cut-off points for fasting insulin, homeostatic model assessment of insulin resistance and two-hour oral glucose tolerance test insulin were very similar in almost all the definitions considered and had adequate diagnostic performance: area under the curve >0.869, sensitivity >0.835 and specificity >0.755. Insulin resistance surrogates had substantial agreements with Ford, Cook and Salas definitions (Kappa~0.62; agreement~82%); moderate agreement was observed for International Diabetes Federation, Cruz and Ferranti definitions (Kappa~0.41–0.59; agreement~77%).Conclusions:Insulin resistance surrogates may be a better approach for metabolic syndrome assessment in an adolescent population because of reduced variability and a higher predictive value.

The magnitude of obesity and metabolic syndrome among diabetic chronic kidney disease population: A nationwide study.

BackgroundAlthough the prevalence of obesity and metabolic syndrome (MetS) among dialysis patients has been exceeding than general population, little is known regarding obesity and MetS in non-dialysis chronic kidney disease (CKD). We aimed to find the magnitude of obesity and MetS and their associations with impaired renal function among type 2 diabetes mellitus (T2DM) patients.MethodsA national survey of T2DM patients was collected in the Thai National Health Security Office database during 2014–5. The sampling frame was designated as distinct geographic regions throughout the country. A stratified two-stage cluster sampling was used to select the study population. Anthropometry and 12-hour fasting blood samples were obtained by trained personnel. BMI of ≥25 kg/m2 was classified as obesity. MetS was defined as having elevated waist circumference (>90 and >80 cm in men and women, respectively) plus any two of the followings: triglyceride ≥150 mg/dL, HDL-C <40 in men or <50 mg/dL in women, blood pressure ≥130/85 mmHg, and fasting blood sugar ≥100 mg/dL. CKD was defined as an impaired renal function (eGFR <60 mL/min/1.73m2 according to the CKD-EPI equation). Logistic regression analysis was performed to examine the relationship between obesity and MetS with the presence of CKD.ResultsA total of 32,616 diabetic patients were finally recruited from 997 hospitals. The mean age was 61.5±10.9 years with 67.5% women. Of the participants, 35.4% were CKD patients. The prevalence of obesity was 46.5% in CKD and 54.1% in non-CKD patients with T2DM (p<0.001). In contrast, the prevalence of MetS in CKD patients was higher than their non-CKD counterparts (71.3 vs 68.8%, p<0.001). Moreover, there was an association between the prevalence of MetS with CKD stage from 3a to 5 (70.1, 72.3, 73.4, and 72.7%, respectively, p trend = 0.02). MetS, but not obesity, had a significant association with CKD in T2DM patients after adjusting for age, sex, and comorbidities [OR 1.14; 95% CI 1.06–1.22, p<0.001]. When stratified by each component of MetS, only high serum triglyceride and low HDL-C levels were increased in patients with CKD stage 4 and 5 compared with CKD stage 3 (p<0.001) and had a significant relationship with impaired renal function.ConclusionThere were relatively high prevalences of both obesity and MetS in T2DM patients. A higher prevalence of MetS, but lower prevalence of obesity, was observed among diabetic CKD group compared with their non-CKD counterparts. MetS, as a surrogate of insulin resistance, appeared to be more important than obesity in the development of impaired renal function in diabetic population.

Plasma Levels of Myonectin But Not Myostatin or Fibroblast-Derived Growth Factor 21 Are Associated with Insulin Resistance in Adult Humans without Diabetes Mellitus.

Myokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines [myonectin, myostatin, and fibroblast-derived growth factor 21 (FGF-21)] would be associated with direct and indirect indicators of insulin resistance (IR) in individuals who did not have a diagnosis of diabetes. We studied 81 adults of both sexes comprising a wide range of body adiposity and insulin sensitivity. All participants underwent a thorough clinical assessment and a 5-point oral glucose tolerance test with calculation of multiple IR and insulin sensitivity indices. Twenty-one of them additionally underwent a hyperinsulinemic-euglycemic clamp with determination of steady-state whole-body insulin-stimulated glucose disposal ("M"). We compared plasma myokine concentrations across quartiles of IR indices and clinical IR surrogates, and explored the correlation of each myokine with the M-value. Plasma myonectin levels increased monotonically across quartiles of the incremental area under the insulin curve (higher values indicate more IR) (p-trend = 0.021) and decreased monotonically across quartiles of the insulin sensitivity index (ISI - higher values indicate less IR) (p-trend = 0.012). After multivariate adjustment for other relevant determinants of IR (body mass index, age, and sex), the negative association of myonectin with ISI persisted (standardized beta = -0.235, p = 0.023). Myostatin was not associated with any clinical IR indicator or direct IR index measure. In multivariate analyses, FGF-21 showed a trend toward a positive correlation with glucose disposal that did not reach statistical significance (standardized beta = 0.476, p = 0.091). The secretion of myonectin may constitute an attempt at a compensatory mechanism against IR in humans.

Type 2 Diabetes Mellitus and Simple Glucose Metabolism Parameters may Reliably Predict Nonalcoholic Fatty Liver Disease Features.

This study aims to investigate the correlation between features of NAFLD among individuals with morbid obesity and the surrogate IR markers homeostasis model assessment (HOMA), product of triglycerides and glucose (TyG), and triglyceride-to-high-density-lipoprotein ratio (TG/HDL-c). A cross-sectional study, which enrolled 89 individuals who consecutively underwent bariatric surgery from February through December 2015, was conducted. NAFLD was assessed through histological examination of liver biopsies and correlated with the values of HOMA, TyG, and TG/HDL-c and their respective cutoff points for insulin resistance (IR). xThe prevalence of liver steatosis was 68.5%; the affected individuals presented significantly higher fasting glucose levels (p<0.01) and hemoglobin A1c (p<0.01), and a significantly higher prevalence of type 2 diabetes mellitus (T2DM) (p<0.001). Fibrosis occurred in 66.3% of the individuals and was significantly associated with higher levels of HbA1c (p<0.05) and a higher prevalence of T2DM (p<0.05). Steatohepatitis was present in 64% of the individuals and was significantly associated with older age (p<0.05), higher levels of fasting glucose (p<0.05), and a higher prevalence of T2DM (p<0.001). After Bonferroni's adjustment, T2DM was significantly correlated with fibrosis (p<0.01) and steatohepatitis (p<0.001) and older age was significantly correlated with fibrosis (p<0.05). T2DM was the only variable independently associated with fibrosis and steatohepatitis (p<0.05 in both cases). T2DM was a significant predictor of NAFLD features among individuals undergoing bariatric surgery; higher Hb A1c was correlated with fibrosis. T2DM was independently associated with fibrosis and steatohepatitis. HOMA, TyG, and TG/HDL-c ratio did not present significant associations with NAFLD.

Comparison of Surrogate Markers as Measures of Uncomplicated Insulin Resistance in Korean Adults.

BackgroundMetabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults.MethodsA cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment–insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods.ResultsThe McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR.ConclusionThe McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required.

Correlation between post over preoperative surrogate insulin resistance indexes' ratios and reversal of metabolic syndrome after Roux-en-Y gastric bypass.

Metabolic syndrome (MetS) is strongly linked to insulin resistance and has a high resolution rate after bariatric surgery. This study aims to determine whether post over preoperative ratios of surrogate insulin resistance markers (HOMA, TyG, and TG/HDL-c) are associated to postsurgical MetS reversal. This is a retrospective cohort study which involved 96 subjects with MetS who underwent Roux-en-Y gastric bypass (RYGB). Post over preoperative ratios of TyG and TG/HDL-c indexes were statistically associated to MetS resolution. The use of these ratios as a way to assess postsurgical insulin sensitivity response appears to be a simple and useful tool in clinical practice.

The [13C]Glucose Breath Test Is a Reliable Method to Identify Insulin Resistance in Mexican Adults Without Diabetes: Comparison with Other Insulin Resistance Surrogates

Insulin resistance (IR) precedes type 2 diabetes, but tests used to detect it in clinical settings reported poor reproducibility. We assessed the reliability of the [(13)C]glucose breath test ((13)C-GBT) in a sample of subjects without diabetes. Repeatability of the test was compared with that of other IR surrogates derived from the fasting or oral glucose tolerance test (OGTT). Eighty-six healthy volunteers received an oral load of 75 g of glucose in 150 mL of water followed by 1.5 mg/kg of [U-(13)C]glucose in 50 mL of water. Breath and blood samples were collected at baseline and at 10, 20, 30, 60, 90, 120, 150, and 180 min following the glucose load; the same procedure was repeated within 1 week. The enrichment of breath (13)CO2 was measured by ratio mass spectrometry and expressed as percentage oxidized dose at a given time period. Intrasubject variability was assessed with Bland-Altman plots and coefficients of variation (CVs). The overall CV of the (13)C-GBT was 12.99±11.61%, compared with 18.42% of fasting insulin, 19.44% for homeostasis model assessment, 17.06% of the composite insulin sensitivity index, and 29.99% for insulin in the 2-h oral glucose tolerance test. The variability of the (13)C-GBT tended to be higher in lean (17.40%) than in overweight (10.17%) and obese (12.61%) individuals. The variability of the (13)C-GBT is lower than that of other IR surrogates, making it a reproducible method to estimate insulin sensitivity in overweight and obese adults without diabetes. Because the individuals did not have diabetes but were within a high range of insulin sensitivity, the test should have application in clinical and population-based studies, given the evidence for the utility and limitations of this surrogate.

Sfrp5 correlates with insulin resistance and oxidative stress

Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee. Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed. At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P < 0·05) and with the oxidative stress markers 8-isoprostane (r = 0·44, P < 0·01) and nitrotyrosine (r = 0·52, P < 0·001). Adiponectin showed inverse correlations with several indices of insulin resistance (e.g. HOMA-IR, Stumvoll index; all P < 0·05) and a direct correlation with the anti-atherogenic apolipoprotein A-I (r = 0·56, P < 0·001). Coffee did not affect serum concentrations of Sfrp5. Serum Wnt5a concentrations were below the detection limit (0·02 ng/mL) in 81% of the study participants. In contrast to obese mouse models, serum Sfrp5 was directly related to HOMA-IR and oxidative stress in humans, but not with apolipoproteins, and thus, associations differed from those found for circulating adiponectin. These differences between Sfrp5 and adiponectin might be explained by differences in the investigated species.