Lipoprotein Insulin Resistance Score and Mortality Risk Stratification in Heart Failure.

BACKGROUND: Higher total serum cholesterol is associated with lower mortality in heart failure. Evaluating associations between lipoprotein subfractions and mortality among people with heart failure may provide insights into this observation. METHODS: We prospectively enrolled a community cohort of people with heart failure from 2003 to 2012 and assessed vital status through 2021. Plasma collected at enrollment was used to measure lipoprotein subfractions via nuclear magnetic resonance spectroscopy. A composite score of 6 lipoprotein subfractions was generated using the lipoprotein insulin resistance index (LP-IR) algorithm. Using covariate-adjusted proportional hazards regression models, we evaluated associations between LP-IR score and all-cause mortality. RESULTS: Among 1382 patients with heart failure (median follow-up 13.9 years), a one-standard-deviation (SD) increment in LP-IR score was associated with lower mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.97-0.99). Among LP-IR parameters, mean high-density lipoprotein (HDL) particle size was significantly associated with lower mortality (HR per 1-SD decrement in mean HDL particle size = 0.83; 95% CI, 0.78-0.89), suggesting that the inverse association between LP-IR score and mortality may be driven by smaller mean HDL particle size. CONCLUSIONS: LP-IR score was inversely associated with mortality among patients with heart failure and may be driven by smaller HDL particle size.

Analysis of Sex Hormones, Insulin Dosage, and Risk Factors Associated With Male Diabetic Patients.

The purpose of this study is to assess the influence of sex hormones and other indicators on risk factors for hypercoagulable states in male patients with type 2 diabetes mellitus. Ninety-two diabetic patients were divided into two groups based on testosterone levels: T1 group (testosterone <12 mmol/L) and T2 group (testosterone >12 mmol/L). Fifty-four non-diabetic patients were used as the control group. Sex hormone index, glucose, insulin, C-peptide, 24-h urinary free cortisol, thromboelastography, and insulin resistance index were measured by radioimmunoassay. Testosterone was lower in the diabetic men than in the control group (12.02 vs 14.77, p < .05), and was inversely related to blood coagulation status, blood glucose level, and cortisol level. Body mass index was positively correlated with estradiol and insulin resistance index. Testosterone was independently associated with the clotting process after controlling for age. Low testosterone is a risk factor for hypercoagulable state in diabetic men. Elevated estradiol and insulin resistance are influential factors for increased body mass index.

The association between the metabolic score for insulin resistance (METS-IR) index and urinary incontinence in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2001-2018.

BACKGROUND: The association between insulin resistance and urinary incontinence (UI) has not been investigated widely. The purpose of this study is to assess the relationship between a novel indicator for assessing insulin resistance the metabolic score for insulin resistance (METS-IR) index and urinary incontinence (UI). METHODS: This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2001-2018. Weighted multivariable logistic regression models were conducted to explore the association of METS-IR index with three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. Smooth curve fitting was utilized to investigate the linear relationship. Subgroup analysis was used to examine the stability of the connection between METS-IR index and UI in different stratifications. RESULTS: A total of 17,474 participants were included in this study, of whom 23.76% had SUI, 20.05% had UUI, and 9.59% had MUI. METS-IR index was positively associated with three types of UI with full adjustment [SUI: odds ratio (OR) = 1.023, 95% confidence interval (CI) 1.019-1.027; UUI: OR = 1.015, 95% CI 1.011-1.019; MUI: OR = 1.020, 95% CI 1.016-1.025, all p < 0.001]. After transferring METS-IR index into a categorical variable by quartiles, the positive connection between METS-IR index and UI was still observed in the highest METS-IR group compared to the lowest METS-IR interval (SUI: OR = 2.266, 95% CI 1.947-2.637, p < 0.001; UUI: OR = 1.534, 95% CI 1.344-1.750, p < 0.001; MUI: OR = 2.044, 95% CI 1.707-2.448, p < 0.001). The analysis of smooth curves fitting showed that METS-IR index was positively linearly related to three types of UI. Moreover, the association between METS-IR index and SUI was more significant in females compared to males (p for interaction < 0.05). CONCLUSION: An elevated METS-IR index was related to increased risks of three types of UI (SUI, UUI, and MUI) in the United States population. METS-IR index was more significantly connected to SUI in females than males. The association between insulin resistance and UI needs to be explored with more studies.

High-Intensity Interval Training in Female Adolescents with Moderate or Severe Obesity.

This study aimed to investigate the impact of moderate- or high-intensity interval training (MIIT or HIIT) on anthropometric and biological measurements in four groups of females with obesity. Fifty-seven participants were divided into a moderate obesity group (MOG, n = 29) and a severe obesity group (SOG, n = 28). Two sub-groups were established to practice HIIT and MIIT programs (SOGHI, n = 14; SOGMI, n = 14; MOGHI, n = 14; MOGMI, n = 15). During the training sessions, each group performed two sets of 4 × 1 min intervals on a cycle ergometer. The intervals were conducted at 65% and 85% of the heart rate reserve (HRR) for MIIT and HIIT, respectively. Between each repetition, there was an active recovery phase at 50% HRR, and, between sets, there was a 4 min period of free pedaling. All groups significantly improved their anthropometric data, while only MOGHI and SOGHI significantly improved their lean body mass (LBM) and blood lactate (BL), with p ˂ 0.05; the higher percentage of change in blood insulin levels (-25.49 and -25.34) and the homeostasis model assessment of the insulin resistance index (-31.42 and -28.88) were noted. Only MOGHI showed improvements in growth hormone (GH) and blood glucose (p < 0.05), which were negatively correlated with body fat percentage (r = -0.76 and r = -0.72) and waist circumference (r = -0.77 and r = -0.82), respectively. We may conclude that HIIT was an effective method of managing anthropometric and biological parameters, as confirmed by the pronounced body fat reduction in the moderate obesity group.

The Triglycerides and Glucose Index: A Cost-Effectiveness Analysis Compared With the Homeostatic Model Assessment for Insulin Resistance.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the triglycerides and glucose index (TyG) versus the homeostatic model assessment for insulin resistance index (HOMA-IR) for diagnosing insulin resistance. METHODS: A cost-effectiveness analysis using a decision tree based on the false-negative and false-positive tests and the true-positive and true-negative tests of both the TyG and HOMA-IR was conducted. Based on the costs and effectiveness of both tests, the average and incremental cost-effectiveness ratios were calculated. Furthermore, one-way sensitivity analysis was conducted regarding sensitivity of both indexes. Using the Monte Carlo simulation with 10 000 iterations, a probabilistic sensitivity analysis that included sensitivity, specificity, and cost of diagnostic tests was conducted. Finally, using the α and ß values obtained from the primary data, the beta distribution was used for estimation of sensitivity and specificity. RESULTS: The cost-effectiveness per test was $1.64 versus $4.26 for TyG and HOMA-IR. The effectiveness of true-positive (0.77 vs 0.74) and true-negative (0.17 vs 0.15) tests was higher for the TyG than HOMA-IR. The cost-effectiveness ratio was lower for the TyG than the HOMA-IR, for both the true-positive ($1.64 vs $4.26) and true-negative ($7.33 vs $20.70) tests. Diagnosing IR using the TyG was 61.5% lower than using the HOMA-IR. CONCLUSIONS: Our findings indicate that the TyG is a high effectiveness and cost-effective test for diagnosing insulin resistance than the HOMA-IR.

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5 g/day of fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups' blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (homeostasis model assessment ratio [HOMA-R]) than the placebo group. In addition, the percentage changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

[Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population].

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes.

Aim: To evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes. Methods: Women (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups. Results: Blood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment (P < 0.05), and there was no statistical difference in the blood glucose levels, biochemical index and HOMA-IR between the two groups (P > 0.05). The CER levels did not differ statistically between the two groups (P > 0.05). Both the cost and the incidence of drug side effects during solution injection were lower in the observation group than in the control group after 24 weeks of treatment (P < 0.05). Conclusion: Both Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe. Clinical trial registration: https://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026514.

Adipose Tissue Insulin Resistance Predicts the Severity of Liver Fibrosis in Patients With Type 2 Diabetes and NAFLD.

CONTEXT: Although type 2 diabetes (T2D) is a risk factor for liver fibrosis in nonalcoholic fatty liver disease (NAFLD), the specific contribution of insulin resistance (IR) relative to other factors is unknown. OBJECTIVE: Assess the impact on liver fibrosis in NAFLD of adipose tissue (adipose tissue insulin resistance index [adipo-IR]) and liver (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]) IR in people with T2D and NAFLD. DESIGN: Participants were screened by elastography in the outpatient clinics for hepatic steatosis and fibrosis, including routine metabolites, cytokeratin-18 (a marker of hepatocyte apoptosis/steatohepatitis), and HOMA-IR/adipo-IR. SETTING: University ambulatory care practice. PARTICIPANTS: A total of 483 participants with T2D. INTERVENTION: Screening for steatosis and fibrosis with elastography. MAIN OUTCOME MEASURES: Liver steatosis (controlled attenuation parameter), fibrosis (liver stiffness measurement), and measurements of IR (adipo-IR, HOMA-IR) and fibrosis (cytokeratin-18). RESULTS: Clinically significant liver fibrosis (stage F ≥ 2 = liver stiffness measurement ≥8.0 kPa) was found in 11%, having more features of the metabolic syndrome, lower adiponectin, and higher aspartate aminotransferase (AST), alanine aminotransferase, liver fat, and cytokeratin-18 (P < 0.05-0.01). In multivariable analysis including just clinical variables (model 1), obesity (body mass index [BMI]) had the strongest association with fibrosis (odds ratio, 2.56; CI, 1.87-3.50; P < 0.01). When metabolic measurements and cytokeratin-18 were included (model 2), only BMI, AST, and liver fat remained significant. When fibrosis stage was adjusted for BMI, AST, and steatosis (model 3), only Adipo-IR remained strongly associated with fibrosis (OR, 1.51; CI, 1.05-2.16; P = 0.03), but not BMI, hepatic IR, or steatosis. CONCLUSIONS: These findings pinpoint to the central role of dysfunctional, insulin-resistant adipose tissue to advanced fibrosis in T2D, beyond simply BMI or steatosis. The clinical implication is that targeting adipose tissue should be the priority of treatment in NAFLD.

Effect of histone deacetylase inhibitor (vorinostat) on new-onset diabetes induced by tacrolimus.

Objective: The immunosuppressant tacrolimus is a major cause of new-onset diabetes after transplantation. The aim of this study was to evaluate whether a low dose of the histone-deacetylase inhibitor (vorinostat) might ameliorate tacrolimus-induced new-onset diabetes. Methods: Thirty 8-week-old male Wistar rats were randomly divided into five groups: a control group, tacrolimus group (1.5 mg/kg intraperitoneally for 28 days), vorinostat group (15 mg/kg orally for 28 days), a group receiving tacrolimus with vorinostat for 28 days; and a group receiving coadministration of tacrolimus for 28 days and vorinostat for 14 days. Diabetes development was assessed on the basis of serum glucose, insulin, HOMA-IR and C-peptide. To investigate the mechanism of vorinostat, we assessed inflammatory markers (tumor necrosis factor-α and interleukin-1ß), an antioxidant marker (glutathione), an oxidant marker (nicotinamide adenine dinucleotide phosphate hydrogen oxidase) and an apoptosis marker (caspase-3). Kidney functions (creatinine and blood urea nitrogen) were also assessed. Results: The administration of tacrolimus for 28 days resulted in significantly increased serum glucose and decreased C-peptide and insulin levels than those in the control group. However, coadministration of vorinostat significantly decreased hyperglycemia and increased C-peptide and insulin levels. Moreover, combined treatment with tacrolimus and vorinostat, compared with tacrolimus treatment alone, resulted in significantly reduced inflammatory and oxidant markers, and increased glutathione. Additionally, vorinostat improved the kidney parameters. Conclusion: Vorinostat at a low dose (15 mg/kg) induces anti-inflammatory and antioxidative effects that protect the pancreas and kidney against the development of new-onset diabetes due to tacrolimus in rats. This experimental study provides insights supporting further clinical trials to improve the post-kidney transplantation protocol through addition of vorinostat to the immunosuppressive regimen.

The Metabolic Score for Insulin Resistance Index is Superior to the Triglyceride and Glucose Index in Identifying Nonalcoholic Fatty Liver Disease in Hyperuricemia Subjects.

Purpose: Hyperuricemia (HUA) is a recognized risk factor for non-alcoholic fatty liver disease (NAFLD). Early diagnosis and the identification of predictive factors are important for the HUA population. This study aimed to investigate the potential relationship between the metabolic score for insulin resistance (METS-IR) index and the triglyceride and glucose (TyG) index with NAFLD in individuals with HUA. Patients and Methods: A total of 5537 HUA participants were included in the study. Hepatic ultrasonography was conducted following the latest diagnostic criteria to diagnose NAFLD. The relationship between the TyG and METS-IR index and NAFLD was evaluated by multivariable logistic regression analysis and restricted cubic spline model (RCS). In addition, the area under the curve (AUC), positive likelihood ratio, and negative likelihood ratio were explored to compare the predictive value of IR surrogates for NAFLD with HUA. The AUCs of the two indicators were compared using the DeLong test. Results: Multivariable logistic regression analysis revealed that elevated TyG (OR = 2.285, 95% CI: 1.525, 3.428) and METS-IR (OR = 1.242, 95% CI: 1.219, 1.266) indices significantly increase the risk of NAFLD. Meanwhile, the RCS analysis revealed a -log-shaped nonlinear relationship between NAFLD risk and the METS-IR index (P non-linear < 0.001), contrasting with the linear association observed with the TyG index (P non-linear = 0.763). Notably, the risk of NAFLD demonstrated a significant escalation when the METS-IR index exceeded the threshold of 39.208 (OR=1). Compared to the TyG index (AUC = 0.734, 95% CI: 0.721~0.748), the METS-IR index (AUC = 0.821, 95% CI: 0.810~0.832) demonstrated superior predictive value for NAFLD in individuals with HUA according to the DeLong test. Conclusion: In the HUA population, the METS-IR index has a higher predictive value for NAFLD than the TyG index, contributing to early diagnosis and disease prevention.

Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population / 中国医学科学院学报

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

The Effect of Acute Intermittent and Continuous Hypoxia on Plasma Circulating ßOHB Levels Under Different Feeding Statuses in Humans.

Introduction: Acute hypoxia is known to increase circulating nonesterified fatty acid (NEFA) levels. Adipose tissue lipolysis is a major source of NEFA into circulation and insulin suppresses this process when the tissue is insulin sensitive. NEFA can be esterified to triglycerides and/or completely/partially oxidized, the latter leading to ketogenesis in the liver. To our knowledge, the effect of hypoxia on ketogenesis, more specifically ß-hydroxybutyrate (ßOHB) levels, remains unknown in humans. Therefore, the objective of this study was to determine the effect of acute intermittent and continuous hypoxia on circulating ßOHB levels under different feeding status. Methods: Plasma samples from three different randomized crossover studies were assessed for ßOHB concentrations. In the first study, 14 healthy men (23 ± 3.5 years) were exposed to 6 h of normoxia or intermittent hypoxia (IH-Fed) (15 hypoxic events/hour) following an isocaloric meal. In the second study, 10 healthy men (26 ± 5.6 years) were exposed to 6 h of continuous normobaric hypoxia (CH-Fasted) (FiO2 = 0.12) or normoxia in the fasting state. In the third study (CH-Fed), 9 healthy men (24 ± 4.5 years) were exposed to 6 h of normoxia or CH in a constant prandial state. ßOHB, NEFA and insulin levels were measured during all sessions. Results: In the IH-Fed study, ßOHB and NEFA levels tended to be greater over 6 h of IH (condition × time interaction, ßOHB p = 0.108 and NEFA p = 0.062) compared to normoxia. In the CH-Fasted study, ßOHB and NEFA levels increased over time in both experimental conditions, this effect being greater under CH (condition × time interaction, ßOHB p = 0.070; NEFA p = 0.046). In the CH-Fed study, ßOHB levels slightly increased up to 180 min before falling back to initial concentrations by the end of the protocol in both normoxia and CH (main effect of time, p = 0.062), while NEFA were significantly higher under CH (p = 0.006). Conclusion: Acute normobaric hypoxia exposure tends to increase plasma ßOHB concentrations over time in healthy men. The stimulating effect of hypoxia on plasma ßOHB levels is however attenuated during postprandial and prandial states.

Insulin Resistance in Gestational Diabetes Mellitus and Its Association With Anthropometric Fetal Indices.

Background: In pregnant women with gestational diabetes mellitus (GDM), insulin resistance (IR) increases the risk of developing manifest type 2 diabetes mellitus and is associated with complications in both mother and fetus. Objectives: This research aimed to evaluate the associations between IR evaluated by 3 indices (namely updated homeostasis model assessment model (HOMA2), QUICKI, and McAuley's index) and the diabetes risk factors and the fetal growth indices in Vietnamese women with GDM. Methods: A cross-sectional descriptive study was conducted on 370 women with GDM and 40 healthy pregnant women from January 2015 to May 2019. IR was calculated by HOMA2 (HOMA2-IR), QUICKI, and McAuley's index. Fetal anthropometric measurements were assessed via ultrasound which was performed and interpreted by ultrasound experts. Results: In the simple regression analysis, McAuley's index illustrated had statistically significant correlations to the highest number of risk factors of diabetes mellitus compared with HOMA2-IR and QUICKI indices. Moreover, McAuley's index correlated statistically significantly to the highest number of fetal ultrasound measurements factors such as including biparietal diameter (BPD) (r = -0.271, P < .001), head circumference (HC) (r = -0.225, P < .001), abdominal circumference (AC) (r = -0.214, P < .001), femur length (FL) (r = -0.231, P < .001), estimated fetal weight (EFW) (r = -0.239, P < .001) and fetal estimated age (r = -0.299, P < .001). In the multivariable analysis, the McAuley's index contributed the greatest to AC (Standardized B of -0.656, P < .001). Conclusion: The McAuley's index was significantly associated with a higher number of more risk factors for diabetes mellitus as well as fetal ultrasound sonography findings measurements than compared with HOMA2-IR and QUICKI indices.

Effects of Physical Exercise on Cardiometabolic Biomarkers and Inflammatory Markers in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The prevalence of obesity among children as well as the beneficial effects of physical exercise (PE) on weight loss has been determined by modulating the secretory factors of adipose tissue. PE has also been shown to have beneficial effects on obesity. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effects of physical exercise (PE) on adiponectin and other important health markers in children. DATA SOURCES: We searched 6 electronic databases (PubMed/Medline, Embase, Cochrane Library, Cinahl, Scopus, and Web of Science) and Google Scholar for randomized controlled trials from inception to December 15, 2021. We used random-effects models to estimate weighted mean difference (WMD) with 95% confidence intervals (CI). STUDY SELECTION: Fourteen studies were included (N = 468 participants; mean age: 14 years). RESULTS: In general, PE increased adiponectin (WMD: 0.91 µg/mL; 95% CI, 0.27 to 1.55, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (WMD: 1.01 mg/dL; 95% CI, 0.33 to 1.69, p = 0.004), and VO2max (WMD: 2.52 mL.kg.min; 95% CI, 1.41 to 3.62, p = 0.00,001). The levels of c-reactive protein (WMD: -0.37 mg/L; 95% CI, -0.57 to -0.17, p = 0.0003), insulin (WMD: -4.61 µIU/ml; 95% CI, -5.46 to -3.76, p = 0.00,001), fasting glucose (WMD: -5.11 mg/dL; 95% CI, -7.88 to -2.34, p = 0.0003), and insulin resistance index (WMD: -1.44; 95% CI, -1.92 to -0.96, p = 0.00,001), decreased significantly. CONCLUSION: Our study showed that PE may increase the level of adiponectin, HDL-C, and VO2max in children.

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease.

Background: Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and Methods: Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. Results: SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). Conclusion: SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.

Associations Between the Metabolic Score for Insulin Resistance Index and the Risk of Type 2 Diabetes Mellitus Among Non-Obese Adults: Insights from a Population-Based Cohort Study.

PURPOSE: The metabolic score for insulin resistance (METS-IR) index is an emerging surrogate predictor of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the METS-IR index and the risk of T2DM in non-obese Japanese adults. METHODS: A total of 12,290 non-obese participants were selected from the NAGALA prospective cohort study conducted from 2004 to 2015. Cox proportional hazards models were used to assess the association between the baseline METS-IR index and risk of T2DM. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 2050 days, 176 (1.43%) incident T2DM occurred. The fully adjusted HR (95% CI) for the incidence of T2DM in non-obese adults was 1.17 (HR=1.17, 95% CI: 1.09-1.27, P<0.001) for every 1-unit increase in the METS-IR index. The risk of developing T2DM increased with the quartile of change in the METS-IR index, after adjustment for multiple potential confounding, the HRs for the Q4 group versus the Q1 group was 4.01 (95% CI, 1.39-11.57). Generalized additive models also showed a cumulative increase in the risk of T2DM with increasing the METS-IR index. Time-dependent receiver operating curve suggested helpful discriminative power of the METS-IR index for T2DM. The C-statistics by the clinical risk factors significantly improve with the addition of the METS-IR index (from 0.862 to 0.875, P = 0.035); the discriminatory power and risk reclassification also appeared to be substantially better, with the category-free NRI of 0.216, and the IDI of 0.011. CONCLUSION: The METS-IR index was a significant and independent predictor for future T2DM development in non-obese adults. The METS-IR index may have clinical significance in identifying groups at high risk of T2DM.

Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial.

In order to assess whether previous hepatic IR (Hepatic-IRfasting) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose-lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the American Diabetes Association recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after oral glucose tolerance test, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IRfasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IRfasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a 5-year follow-up. Low-Hepatic-IRfasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IRfasting or low-DI subjects (HR:1.79; 95% CI 1.06-3.05; and HR:2.66; 95% CI 1.60-4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low-Hepatic-IRfasting and high-DI presented the highest probability of remission (HR:4.63; 95% CI 2.00-10.70). Among patients maintaining diabetes, those with high- Hepatic-IRfasting and low-DI showed the highest risk of starting glucose-lowering therapy (HR:3.24;95% CI 1.50-7.02). Newly-diagnosed type 2 diabetes patients with better beta-cell functionality and lower Hepatic-IRfasting had a higher probability of type 2 diabetes remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse beta-cell functionality and higher Hepatic-IRfasting index had the highest risk of starting glucose-lowering treatment after 5 years of follow-up.

Nuclear Magnetic Resonance Derived Biomarkers for Evaluating Cardiometabolic Risk in Youth and Young Adults Across the Spectrum of Glucose Tolerance.

Youth with obesity have an increased risk for cardiometabolic disease, but identifying those at highest risk remains a challenge. Four biomarkers that might serve this purpose are "by products" of clinical NMR LipoProfile® lipid testing: LPIR (Lipoprotein Insulin Resistance Index), GlycA (inflammation marker), BCAA (total branched-chain amino acids), and glycine. All are strongly related to insulin resistance and type 2 diabetes (T2DM) in adults (glycine inversely) and are independent of biological and methodological variations in insulin assays. However, their clinical utility in youth is unclear. We compared fasting levels of these biomarkers in 186 youth (42 lean normal glucose tolerant (NGT), 88 obese NGT, 23 with prediabetes (PreDM), and 33 with T2DM. All four biomarkers were associated with obesity and glycemia in youth. LPIR and GlycA were highest in youth with PreDM and T2DM, whereas glycine was lowest in youth with T2DM. While all four were correlated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LPIR had the strongest correlation (LPIR: r = 0.6; GlycA: r = 0.4, glycine: r = -0.4, BCAA: r = 0.2, all P < 0.01). All four markers correlated with HbA1c (LPIR, GlycA, BCAA: r ≥ 0.3 and glycine: r = -0.3, all P < 0.001). In multi-variable regression models, LPIR, GlycA, and glycine were independently associated with HOMA-IR (Adjusted R2 = 0.473, P < 0.001) and LPIR, glycine, and BCAA were independently associated with HbA1c (Adjusted R2 = 0.33, P < 0.001). An LPIR index of >44 was associated with elevated blood pressure, BMI, and dyslipidemia. Plasma NMR-derived markers were related to adverse markers of cardiometabolic risk in youth. LPIR, either alone or in combination with GlycA, should be explored as a non-insulin dependent predictive tool for development of insulin resistance and diabetes in youth. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT:02960659.

Effect of Korean Red Ginseng on metabolic syndrome.

Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.