Higher Homeostasis Model Assessment For Insulin Resistance Research Articles

P-633 Impact of insulin resistance on reproductive medicine outcomes

Abstract Study question Does Homeostasis Model Assessment for insulin resistance (HOMA-IR) have an influence in reproductive medicine outcomes? Summary answer HOMA-IR is associated with fertility treatment parameters and has a significant influence on reproductive medicine outcomes. What is known already The HOMA model is used to yield an estimate of insulin sensitivity from basal (fasting) plasma insulin and glucose concentrations. Currently, the model has become a widely used clinical tool to evaluate glucose metabolism. Regarding fertility, the relation between polycystic ovary syndrome (PCOS) and insulin resistance (IR) has been studied. Insulin resistance may be potential contributor to impaired treatment outcomes in artificial reproductive technology (ART). Although a few studies have recently been published on the topic the association of HOMA-IR with fertility treatment parameters remains a black box in reproductive medicine research. Study design, size, duration The observational study was designed and conducted at the Kinderwunsch Institut Schenk GmbH (Dobl, Austria). The study included 175 patients (25 men and 150 women), aged 18-45. HOMA-IR was determined for each patient and then correlated with patient’s medical history, fertility treatment parameters and outcomes. Participants/materials, setting, methods HOMA-IR was determined by taking a blood sample during fasting state and measuring plasma values of glucose (mg/dl) and insulin (mU/ml). A HOMA-IR of ≥ 2 was considered as insulin resistance. HOMA-IR was correlated with medical history (polycystic ovarian syndrome (PCOS), endometriosis, Body-Mass-Index (BMI), nicotine abuse) and fertility treatment parameters (sperm quality, number of retrieved oocytes after controlled ovarian stimulation, number of mature and fertilized oocytes, embryo quality and pregnancy rate). Main results and the role of chance An increased HOMA-IR (³2) was observed in 90 patients (51.4%). They suffered from obesity (n = 36; 80%), PCOS (n = 22; 70.97%), ovarian hyperstimulation syndrome (n = 17; 77.27%) and experienced poor embryo quality (n = 249; 91.54%). A significant positive correlation was found between HOMA-IR and PCOS (p < 0.001), obesity (p < 0.001) and number of retrieved oocytes (p < 0.05). The pregnancy rate correlated negatively with the HOMA-IR (p < 0.001). Furthermore, trends of positive correlations of high HOMA-IR in endometriosis, BMI, pathological spermiogram, nicotine abuse and increased number of mature oocytes were determined. The relation between HOMA-IR and the number of retrieved and mature oocytes is consistent with its relation to PCOS. The data show that HOMA-IR is associated with fertility treatment parameters and has a significant influence on ART outcome. Limitations, reasons for caution The number of patients may be seen as a study limitation. Results should be confirmed with a bigger sample size. An interventional study should confirm the role of HOMA-IR in IVF outcomes. Wider implications of the findings These findings may help to better understand the importance of glucose and insulin metabolism in reproduction and suggest that evaluation of HOMA-IR may be a valuable parameter to be considered when collecting patients’ anamnesis prior to starting ART treatment. Trial registration number not applicable

Abstract MP30: Sugar-Sweetened Beverages, Fruit Juices, and Whole Fruits Throughout Childhood and Adolescence and Glycemic Outcomes in Late Adolescence in Project Viva

Objective: To investigate sex-specific associations of sugar-sweetened beverages (SSBs), 100% fruit juices, and whole fruit intake throughout childhood and adolescence with insulin resistance and glycemic outcomes in late adolescence. Methods: We used data from Project Viva, an ongoing pre-birth cohort from eastern Massachusetts. We evaluated intake of SSBs, 100% fruit juices, and whole fruit at early childhood (median age: 3.1 yrs), mid-childhood (7.6 yrs) and early teen research visits (12.9 yrs) using food frequency questionnaires. We measured fasting blood glucose, insulin and glycated hemoglobin (HbA1c) levels in late adolescence (17.4 yrs). We estimated insulin resistance with the homeostasis model assessment for insulin resistance (HOMA-IR). We computed sex-specific linear regression models to estimate associations of average consumption of SSBs, fruit juice and whole fruit across the 3 childhood-early teen visits with late adolescence HOMA-IR, fasting glucose and HbA1c adjusting for demographics, socioeconomic status, mother BMI, child BMI z-score, and parental history of type 2 diabetes in early childhood (model 1), and additionally for lifestyle habits and diet quality in early childhood (model 2). Results: A total of 240 girls and 215 boys met eligibility criteria and had an outcome measure in late adolescence. Greater SSB intake throughout childhood and adolescence was associated with higher HOMA-IR, fasting glucose, and HbA1c in boys only (Figure). Also in boys, greater fruit juice intake was associated with higher HbA1c in late adolescence. Effect estimates in girls were of small magnitude and centered to the null, except for fruit juice and HbA1c with associations in the same direction as boys (Figure). We did not observe any association with respect to whole fruits for either sex. Conclusion: Findings suggest that SSBs and fruit juice consumption throughout childhood and adolescence are associated with less favorable glycemic traits in boys, suggesting greater risk of developing diabetes.

Prospective study of the association between chronotype and cardiometabolic risk among Chinese young adults

BackgroundThe association of evening chronotype with cardiometabolic disease has been well established. However, the extent to which circadian rhythm disturbances independently result in risk remains unclear. This study aimed to investigate the cross-sectional and prospective longitudinal associations between chronotype and cardiometabolic risk among Chinese young adults.MethodsFrom April to May 2019, a total of 1 135 young adults were selected to complete the self-administered questionnaire, and 744 fasting blood samples were collected to quantify cardiometabolic parameters. From April to May 2021, 340 fasting blood samples were collected to quantify cardiometabolic parameters. The Morning and Evening Questionnaire 5 (MEQ-5) was used to assess chronotype. The cardiometabolic (CM)-risk score was the sum of standardized Z scores based on gender for the 5 indicators: waist circumference (WC), mean arterial pressure (MAP), triglyceride (TG), homeostasis model assessment for insulin resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C), where the HDL-C is multiplied by-1. The generalized linear model was used to determine the cross-sectional and prospective longitudinal associations between chronotype and each cardiometabolic parameter.ResultsCross-sectional association analysis showed that lower MEQ-5 scores were correlated with higher fasting insulin (β=-1.420, 95%CI: -2.386~-0.453), higher HOMA-IR (β=-0.301, 95%CI: -0.507~-0.095), and higher CM risk score (β=-0.063, 95%CI: -0.122~-0.003), even after adjustment for covariates. Prospective longitudinal association analysis also showed that lower MEQ-5 scores were associated with 2 years later higher fasting glucose (β=-0.018, 95%CI: -0.034~-0.003), higher fasting insulin (β=-0.384, 95%CI: -0.766~-0.003), higher HOMA-IR (β=-0.089, 95%CI: -0.176~-0.002), and higher CM-risk score (β=-0.109, 95%CI: -0.214~-0.003) after adjustment for covariates.ConclusionsEvening chronotype was significantly correlated with higher CM risk among young adults. Our findings suggest that biologically and socially affected sleep timing misalignment is a contributing factor to cardiovascular disease risk.

Factors Influencing Blood Prolactin Levels in Patients with Schizophrenia under Risperidone Treatment

Abstract Objectives: Risperidone, a dopamine and serotonin antagonist or a second-generation (atypical) antipsychotic drug, is commonly prescribed for various psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders. While effective, risperidone often leads to hyperprolactinemia, impacting about 40%–80% of patients. In this study, we intended to examine the prevalence of hyperprolactinemia in Taiwanese patients with schizophrenia who received risperidone medication and to analyze potential links between prolactin blood levels and clinical variables. Methods: Patients with schizophrenia receiving risperidone monotherapy were included in this cross-sectional study. Blood levels of prolactin and metabolic parameters were measured. Results: A total of 176 participants diagnosed with schizophrenia, including 87 women and 89 men, were enrolled in our study. The prevalence of hyperprolactinemia and metabolic syndrome was 75.6% and 31.8%, respectively. Patients with hyperprolactinemia showed significantly higher insulin blood levels (p < 0.05) and significantly higher homeostasis model assessment for insulin resistance (HOMA-IR) indexes (p < 0.05) than those without hyperprolactinemia. The results of multivariate linear regression analysis showed that female sex (p = 0.001), HOMA-IR index (p < 0.01), and risperidone daily dosage (p < 0.05) were significantly associated with prolactin blood level. Conclusion: This study adds to the existing knowledge concerning risperidone-induced hyperprolactinemia in Taiwanese patients with schizophrenia. Hyperprolactinemia and metabolic syndrome are prevalent in patients with schizophrenia treated with risperidone. Clinicians are advised to be aware of these problems and monitor them regularly with their patients who receive treatment with risperidone.

Metabolic disturbances in children with narcolepsy: a retrospective study.

To determine the prevalence of metabolic syndrome (MS) in children with narcolepsy and to evaluate their clinical and sleep characteristics according to the different components of MS. This retrospective study consisted of 58 de novo children with narcolepsy (median age: 12.7 years, 48.3% of boys). The recently published MS criteria in a French population of children were used. Clinical and sleep characteristics were compared between groups with different components of MS. MS was present in 17.2% of children with narcolepsy, among whom 79.3% presented with high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index, 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Patients with at least two MS components had more night eating behaviors and tended to have lower percentage of slow-wave sleep and more fragmented sleep. On multiple sleep latency test, they had shorter mean sleep latencies to rapid eye movement (REM), non-REM sleep and tended to have more sleep onset REM periods (SOREMPs) than those with less than two MS components. Insulin resistance was found to be the core metabolic disturbance in obese as well as in nonobese children with narcolepsy. Children with narcolepsy with at least two MS components presented a more severe daytime sleepiness and a higher prevalence of night-eating behaviors than those with less than two MS components. Such children might benefit from early evaluation and management in order to prevent future complications.

LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR

Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/β-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and β-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/β-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

Developing a risk assessment tool for identifying individuals at high risk for developing insulin resistance in European adolescents: the HELENA-IR score.

To develop and validate an easy-to-use screening tool for identifying adolescents at high-risk for insulin resistance (IR). Α total of 1,053 adolescents (554 females), aged 12.5 to 17.5 years with complete data on glucose and insulin levels were included. Body mass index (BMI), fat mass index (FMI) and the homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. VO2max was predicted using 20m multi-stage fitness test. The population was randomly separated into two cohorts for the development (n=702) andvalidation (n=351) of the index, respectively. Factors associated with high HOMA-IR were identified by Spearman correlation in the development cohort; multiple logistic regression was performed for all identified independent factors to develop a score index. Finally, receiver operating characteristic (ROC) analysis was performed in the validation cohort and was used to define the cut-off values that could identify adolescents above the 75th and the 95th percentile for HOMA-IR. BMI and VO2max significantly identified high HOMA-IR in males; and FMI, TV watching and VO2max in females. The HELENA-IR index scores range from 0 to 29 for males and 0 to 43 for females. The Area Under the Curve, sensitivity and specificity for identifying males above the 75th and 95th of HOMA-IR percentiles were 0.635 (95%CI: 0.542-0.725), 0.513 and 0.735, and 0.714 (95%CI: 0.499-0.728), 0.625 and 0.905, respectively. For females, the corresponding values were 0.632 (95%CI: 0.538-0.725), 0.568 and 0.652, and 0.708 (95%CI: 0.559-0.725), 0.667 and 0.617, respectively. Simple algorithms were created using the index cut-off scores. Paediatricians or physical education teachers can use easy-to-obtain and non-invasive measures to apply the HELENA-IR score and identify adolescents at high risk for IR, who should be referred for further tests.

The metabolic health of young men conceived using intracytoplasmic sperm injection.

Is the metabolic health of men conceived using ICSI different to that of IVF and spontaneously conceived (SC) men? ICSI-conceived men aged 18-24 years, compared with SC controls, showed differences in some metabolic parameters including higher resting diastolic blood pressure (BP) and homeostasis model assessment for insulin resistance (HOMA-IR) scores, although the metabolic parameters of ICSI- and IVF-conceived singleton men were more comparable. Some studies suggest that IVF-conceived offspring may have poorer cardiovascular and metabolic profiles than SC children. Few studies have examined the metabolic health of ICSI-conceived offspring. This cohort study compared the metabolic health of ICSI-conceived men to IVF-conceived and SC controls who were derived from prior cohorts. Participants included 121 ICSI-conceived men (including 100 singletons), 74 IVF-conceived controls (all singletons) and 688 SC controls (including 662 singletons). Resting systolic and diastolic BP (measured using an automated sphygmomanometer), height, weight, BMI, body surface area and fasting serum metabolic markers including fasting insulin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides, highly sensitive C-reactive protein (hsCRP) and HOMA-IR were compared between groups. Data were analysed using multivariable linear regression adjusted for various covariates including age and education level. After adjusting for covariates, compared to 688 SC controls, 121 ICSI-conceived men had higher diastolic BP (β 4.9, 95% CI 1.1-8.7), lower fasting glucose (β -0.7, 95% CI -0.9 to -0.5), higher fasting insulin (ratio 2.2, 95% CI 1.6-3.0), higher HOMA-IR (ratio 1.9, 95% CI 1.4-2.6), higher HDLC (β 0.2, 95% CI 0.07-0.3) and lower hsCRP (ratio 0.4, 95% CI 0.2-0.7) levels. Compared to 74 IVF-conceived singletons, only glucose differed in the ICSI-conceived singleton men (β -0.4, 95% CI -0.7 to -0.1). No differences were seen in the paternal infertility subgroups. The recruitment rate of ICSI-conceived men in this study was low and potential for recruitment bias exists. The ICSI-conceived men, the IVF-conceived men and SC controls were from different cohorts with different birth years and different geographical locations. Assessment of study groups and controls was not contemporaneous, and the measurements differed for some outcomes (BP, insulin, glucose, lipids and hsCRP). These observations require confirmation in a larger study with a focus on potential mechanisms. Further efforts to identify whether health differences are due to parental characteristics and/or factors related to the ICSI procedure are also necessary. This study was funded by an Australian National Health and Medical Research Council Partnership Grant (NHMRC APP1140706) and was partially funded by the Monash IVF Research and Education Foundation. S.R.C. was supported through an Australian Government Research Training Program Scholarship. R.J.H. is supported by an NHMRC project grant (634457), and J.H. and R.I.M. have been supported by the NHMRC as Senior and Principal Research Fellows respectively (J.H. fellowship number: 1021252; R.I.M. fellowship number: 1022327). L.R. is a minority shareholder and the Group Medical Director for Monash IVF Group, and reports personal fees from Monash IVF Group and Ferring Australia, honoraria from Ferring Australia and travel fees from Merck Serono and MSD and Guerbet; R.J.H. is the Medical Director of Fertility Specialists of Western Australia and has equity in Western IVF; R.I.M. is a consultant for and shareholder of Monash IVF Group and S.R.C. reports personal fees from Besins Healthcare and nonfinancial support from Merck outside of the submitted work. The remaining authors have no conflicts of interest to declare. N/A.

Reproductive and Metabolic Health of Young Men Conceived Using ICSI

Background: Use of ICSI has escalated globally. Concerns include: 1) heritability of infertility, 2) effects of poor-quality spermatozoa on offspring health, 3) epigenetic effects of ICSI procedure. Aim: Compare reproductive and metabolic health of ICSI-conceived men to IVF-conceived and spontaneously conceived (SC) controls. Method: This study is part of a larger project investigating the health and development, reproductive and metabolic health, and epigenetic profiles of ICSI-conceived men (aged 18-25 years). Age-matched IVF-conceived controls were sourced from the Clinical review of the Health of 22–35-year-olds conceived with and without ART (CHART) study; SC controls were derived from the Western Australian Pregnancy Cohort (Raine) study. In subgroup analyses, ICSI-conceived men of fathers with spermatogenic failure (STF-ICSI) were compared with ICSI-conceived men whose fathers had an obstructive cause of infertility, and IVF- and SC controls. Semen parameters and serum reproductive hormones were compared between 120 ICSI-conceived men and 356 SC controls. Resting systolic and diastolic blood pressure (BP), height, weight, BMI, body surface area, and serum metabolic markers were compared between 121 ICSI-conceived men, and 74 IVF-conceived and 688 SC controls. Results: We found no compelling evidence of poorer reproductive health in ICSI-conceived men compared to age-matched SC controls, including a subgroup of STF-ICSI-conceived men. There was no correlation in any of the semen parameters between ICSI fathers and sons, including STF-ICSI father-son pairs. ICSI-conceived men compared with SC controls had higher resting diastolic BP and higher homeostasis model assessment for insulin resistance (HOMA-IR), but a similar proportion had insulin resistance. Metabolic parameters of ICSI-conceived men and IVF-conceived controls were comparable. Conclusion: This study is the largest to date and indicates comparable reproductive health of ICSI-conceived men, including men whose fathers had STF, to a similarly aged population-representative cohort of SC men. It shows few metabolic differences between ICSI-conceived men, and IVF-conceived and SC controls.

The Combination of High Levels of Adiponectin and Insulin Resistance Are Affected by Aging in Non-Obese Old Peoples.

BackgroundAdipokine dysregulation is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Low adiponectin levels are associated with higher risks of cardiovascular diseases (CVD). However, high adiponectin levels have also been associated with increased all-cause and cardiovascular mortality in the elderly. This adiponectin paradox has yet to be clarified, which has hindered our understanding of the biological role of adiponectin. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. The objective of this study was to investigate the association between plasma adiponectin and insulin resistance using the homeostasis model assessment for insulin resistance (HOMA-IR) classified by age. In particular, we sought to determine the factors of the subjects associated with both high adiponectin levels and HOMA-IR (H-adiponectin/H-HOMA) and high adiponectin levels and low HOMA-IR (H-adiponectin/L-HOMA).MethodsThe eligible subjects in this cross-sectional study were 33,216 individuals who had undergone health checkups at the Physical Checkup Center of Sumitomo Hospital between April 2008 and December 2018. After excluding 26,371 individuals who were under 60 years old, 529 who had been taking medications for diabetes mellitus, and 690 with missing data, the present study included 5,673 (3,467 males, 2,206 females) subjects with no missing data. The relationship between serum adiponectin levels and HOMA-IR was assessed using logistic regression models adjusted by clinically relevant factors.ResultsIn the multivariable logistic regression analysis, age and low BMI were shown to positively correlate with the characteristics of H-adiponectin/H-HOMA. In females, systolic blood pressure was also shown to be an associated factor.ConclusionIn conclusion, this study showed that aging or a low BMI may contribute to high adiponectin levels and insulin resistance.

Insulin resistance and associated factors in female adolescents from two capital cities in the north and south of Brazil

BackgroundIt has been described that physiological changes in glucose metabolism, represented by insulin resistance (IR), are predicted during pubertal evolution, and obesity may be associated with its persistence even at the end of puberty. The aim of this study was to investigate the prevalence of IR in female adolescents with possible associated factors and evaluate the relationship of time since menarche (< 2 vs. ≥ 2 years) in the occurrence of IR in two Brazilian capital cities: Porto Velho (RO) and Porto Alegre (RS).MethodsThis is a cross-sectional school-based study, using information from the Study of Cardiovascular Risks (ERICA) database for adolescents aged 12–17 years, enrolled in public and private schools, in municipalities with more than 100,000 inhabitants in Brazil, between 2013 and 2014. The present study included 889 adolescents, 382 in Porto Velho (PVh) and 507 in Porto Alegre (PoA). The homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 3.16 and fasting insulin ≥ 15 mU/L was used to determine the outcome variable of IR. Estimates of crude and adjusted prevalence ratios with confidence intervals of 95% were calculated using Poisson regression with robust variance. Sociodemographic, behavioral, reproductive and nutritional characteristics were considered as potential confounding factors in multivariable models based on a conceptual framework of IR determination.ResultsIn the total sample, the prevalence of IR was 22.03% (95% CI 17.84–26.89). After adjusting the models, age 15–17 years and time since menarche ≥ 2 years were found to act as protective factors for IR; in contrast, the highest probability of IR was observed in black adolescents, with increased waist circumference (WC) and overweight/obesity (Ow/Ob). The protective effect of two or more years since menarche (post-menarche) was observed for both higher HOMA-IR and fasting insulin in PVh; in PoA, such protection was maintained only for fasting insulin ≥ 15 mU/L after adjustments in the multivariate models.ConclusionsIR is more prevalent during the peri-menarche period, especially in younger and black adolescents, compared to their white and post-menarche counterparts. The association between Ow/Ob and high WC with the occurrence of IR was independent of age and ethnicity variables.

Abstract 14300: The Relationship Between the American Heart Association’s Life Simple 7, Ectopic Fat and Insulin Resistance Among South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Introduction: The inverse association between ideal cardiovascular health (CVH) as measured by AHA’s Life simple 7, and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and surrogate markers of cardiometabolic disease, including ectopic fat depots, insulin resistance, and β-cell dysfunction is sparse. Methods: Among 906 South Asian participants (mean age 55 y, SD=9.4, 46% women) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we assigned each LS7 component a score of 0, 1, and 2, and summed these scores to derive an overall CVH score. Visceral, subcutaneous, pericardial, and intermuscular fat and hepatic fat attenuation were measured using computed tomography. We used a homeostasis model assessment for insulin resistance (HOMA-IR) for insulin resistance and HOMA-β for β-cell function. We used multiple linear regression to model the associations between CVH score and natural log-transformed ectopic fat measures, HOMA-IR, and HOMA-β. Results: In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 53.9% (95% CI, 39.7 - 69.4) higher visceral fat area, 66.5% (50.5 - 84.2) higher pericardial fat volume, and 35.1% (23.0 - 48.4) higher subcutaneous fat area, but only 8% (3.1 - 13.0) higher intermuscular fat area and 15.9% (11.2 - 20.4) higher intrahepatic fat (all p&lt;0.001). Also, poor CVH was associated with 154% (117.5 - 198) higher HOMA-IR. Similarly, participants with intermediate CVH demonstrated significantly larger measures of ectopic fat and HOMA-IR. There was no significant association between CVH and HOMA-β. Conclusion: We found that poor and intermediate CVH, as defined by LS7 metrics, was associated with significantly higher measures of ectopic fat and insulin resistance among South Asians. Long-term follow-up of the MASALA cohort will examine the association of LS7 metrics with the incident CVD events.

Serum lipoprotein(a) levels and insulin resistance have opposite effects on fatty liver disease

Background and aimsHigh lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults. MethodsA total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR). ResultsAmong the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p < 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725–0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679–2.158). ConclusionsSerum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.

The Effect of Whole Blood Lead (Pb-B) Levels on Changes in Peripheral Blood Morphology and Selected Biochemical Parameters, and the Severity of Depression in Peri-Menopausal Women at Risk of Metabolic Syndrome or with Metabolic Syndrome.

The aim of our study was to assess the impact of whole blood lead (Pb-B) levels on changes in peripheral blood morphology and selected biochemical parameters, and the severity of depression in peri-menopausal women at risk of metabolic syndrome (pre-MetS) or with metabolic syndrome (MetS). The study involved 233 women from the general population of the West Pomeranian Province (Poland) aged 44–65 years. The intensity of menopausal symptoms and the severity of depression was examined using the Blatt–Kupperman Index (KI) and the Beck Depression Inventory (BDI). C-reactive protein (CRP), insulin, glucose, glycated hemoglobin (HbA1C), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride levels (TG), cortisol, morphology of blood cells and homeostasis model assessment for insulin resistance (HOMA-IR) and Pb-B was measured. Women with MetS had higher levels of glucose, HbA1C, HDL, LDL, TG, cortisol, insulin and higher HOMA-IR. No significant differences in Pb-B were observed between pre-MetS and the control group, and between pre-MetS and the MetS group. A significant correlation was noticed between Pb-B vs. the percentage of monocytes in blood, and blood cortisol levels in women with MetS; Pb-B vs. lymphocyte count and HbA1C in the pre-MetS group, as well as in the BDI scores between the MetS and pre-MetS group. We cannot clearly state that exposure to Pb is an environmental factor that can be considered as a risk factor for MetS in this studied group.

P5665The independent effect of insulin resistance on incidence of atrial fibrillation in non-diabetics

Abstract Purpose Patients with diabetes mellitus have an elevated risk of atrial fibrillation (AF). However, whether insulin resistance may elevate risk of AF incidence in non-diabetic is inconsistent. The aim of our study was to verify the association between insulin resistance and incidence of AF in non-diabetics. Methods We evaluated population-based cohorts embedded in the Korean Genome Epidemiology Study. Insulin resistance was expressed as Homeostasis Model Assessment for Insulin resistance (HOMA-IR). Baseline data including HOMA-IR and electrocardiography (ECG) were obtained at 2001. Subsequent biennial ECG was performed for identification of AF until 2016. Results Among the 8220 participants (46.8% male; median age 49 years), 25 participants had AF (0.3%) at baseline and 101 participants developed AF (1.2%) during follow up of 12 years. In multivariate Cox regression analysis, high HOMA-IR (≥1.4) was significantly associated with incident AF compared with low HOMA-IR (&lt;1.40) (adjusted hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.3–3.0). In subgroup analysis, these association was consistent regardless of obesity (BMI&lt;25; adjust HR 1.8, 95% CI 1.1–3.0, BMI≥25; adjust HR 2.3, 95% CI 1.3–4.0) Subgroup analysis Conclusion Based on prospective cohort study, insulin resistance (HOMA-IR) was associated with AF independently of obesity in non-diabetics.

Insulin resistance and hepatitis C infection: a bidirectional relationship independent of diabetes and metabolic syndrome

Introduction Hepatitis C virus (HCV) infection is known to be associated with insulin resistance (IR). The latter occurs early in the course of the disease and adversely affect it. The mechanism of this association seems to be different from that occurring in the metabolic syndrome. The aim of the study was to test this relationship in non-diabetic patients with early cirrhosis who are not fulfilling the criteria of metabolic syndrome. Patients and methods This cross-sectional study, included 100 patients with Child A cirrhosis induced by HCV. The patients were subjected to clinical, laboratory, ultrasonographic, and endoscopic evaluation. On the basis of homeostasis model assessment for insulin resistance (HOMA-IR) categorization, the patients were divided into two groups, with and without IR. Results A total of 63 patients had a higher HOMA-IR score, hence assigned as group 1, with significant elevation of liver enzymes, less albumin levels and more esophageal varices than in group 2. In a cohort of patients previously eradicated from the virus, HOMA-IR is lower than the non-treated patients. Conclusion Even in the absence of diabetes and metabolic syndrome, IR is evident in nearly two-thirds of patients having early HCV-induced cirrhosis. This link is associated with more inflammation of the liver and more drawbacks on the portal circulation. Sustained clearance of the virus improves insulin sensitivity.

High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto’s thyroiditis

ABSTRACTObjective: To investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels are increased in euthyroid patients with Hashimoto’s thyroiditis (HT) and whether they are associated with thyroid autoimmunity and metabolic parameters. Design: Cross-sectional. Subjects and Methods: In total, 80 euthyroid patients with HT and 80 age- and body mass index (BMI)-matched control participants were included. Serum sICAM-1, sVCAM-1, free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), fasting blood glucose (FBG), insulin, and lipid levels and homeostasis model assessment for insulin resistance (HOMA-IR) were assessed in all participants. Results: The patients with HT had significantly higher levels of sICAM-1 and sVCAM-1 than controls (both p < 0.001). The difference was sustained after adjustment for TSH and levothyroxine use. Regression analysis demonstrated that sICAM-1 was related to anti-TPO (p < 0.001), and sVCAM-1 was related to both anti-TPO and-TG (p < 0.001 and p = 0.03, respectively); this relationship was sustained after adjustment for age and BMI. Although FBG and HOMA-IR were higher in the HT group, logistic regression analysis revealed that there was no effect of anti-TPO, anti-TG, sICAM-1, sVCAM-1, and C-reactive protein (CRP) on the occurrence of high FBG and high HOMA-IR. Conclusion: sICAM-1 and sVCAM-1 levels were significantly elevated in the patients with euthyroid HT and correlated closely with thyroid autoimmunity. However, soluble adhesion molecules had no relation with glucose metabolism parameters in the HT patients.

Abstract P321: Insulin Resistance is Associated with Incident Coronary Heart Disease but Not Stroke Among African Americans: The Jackson Heart Study

Background: The association between the homeostasis model assessment for insulin resistance (HOMA-IR) and CVD varies by race/ethnicity and is often non-existent or weaker in African Americans (AAs). Triglyceride levels (110-149 mg/dl) below the current metabolic syndrome threshold are associated with insulin resistance in AAs, suggesting that the McAuley index (MA index ), based on insulin and triglycerides, may predict CHD and stroke better than HOMA-IR. We investigated this association in the Jackson Heart Study, a large longitudinal cohort of AAs. Methods: Insulin resistance was estimated for 3565 participants without diabetes and CVD at baseline using the MA index (exp [2.63-0.28 In(insulin in mU/l) - 0.31 In(triglycerides in mmol/l)]) and its association with incident CHD and stroke (composite outcome) was compared against that of the HOMA-IR index. A lower MA index and higher HOMA-IR are indicative of insulin resistance. Cox regression analysis was used to estimate adjusted hazard ratios (HR) for incident CHD and stroke, individually and as a composite. Results: There were 158 events (89 CHD-only, 58 stroke-only, and 11 CHD/stroke) over a median follow-up of 8.4 years. After adjustment for demographic factors, the risk of the composite outcome decreased with each SD increase in the MA index (HR 0.80; 95% CI: 0.67 - 0.96), with no attenuation following further control for CHD and stroke risk factors. When considered individually, the MA index was associated with CHD (HR 0.71, 95% CI: 0.55 - 0.92), but not stroke (HR 0.96, 95% CI: 0.74 - 1.25) risk. The log(HOMA-IR)-CHD association was comparable to that observed with the MA index (Table 1). For both indices, an association was present in men, but not in women (P interaction = 0.01 and 0.2 for log(HOMA-IR) and MA index , respectively). Conclusions: The performance of the MA index in predicting CHD and stroke risk in AAs is comparable to the widely used HOMA-IR index. Our findings suggest a role of insulin resistance in CHD but not stroke risk in this population.

Relationship between the weight gain in the first and second trimesters and gestational glucose metabolism

Objective To study the difference of body weight gain in the first and second trimesters between pregnant women with abnormal gestational glucose metabolism and those with normal gestational glucose metabolism. Methods We retrospectively analyzed the data of pregnant women visited the obstetric clinic of Peking Union Medical College Hospital from January 2010 to May 2011, with or without abnormal glucose metabolism. The data of body weight gain in the first and second trimesters, body mass index (BMI) before pregnancy, BMI in the end of second trimester, age, obesity history, diabetes family history, insulin level in the oral glucose tolerance test (OGTT), and lipid profile of these women were collected. Results Altogether 216 pregnant women with abnormal glucose metabolism (case group) and 230 pregnant women with normal glucose metabolism (control group) were included in this study. In the case group, the increment of body weight in the first and second trimesters was 10.0(8.1, 12.5)kg, and the increment of BMI was (4.01±1.43)kg/m2, BMI in the end of the second trimester was (25.84±3.14)kg/m2; in comparison, the increments of body weight and BMI in the first and second trimesters were 9.5 (7.0, 11.5)kg and (3.60±1.43)kg/m2, respectively, BMI in the end of the second trimester was (25.1 ±3.00)kg/m2 in the control group, all significantly lower than in the case group (all P 0.05). Compare with the control group, the case group had older age [(33.17±3.65)years vs. (31.68±3.36)years], higher fasting insulin level [11.2 (7.1, 16.3)mU/L vs. 8.9 (6.5, 13.7)mU/L], higher peak insulin level in OGTT [135.3(99.7, 208.0)mU/L vs. 104.9(75.6, 144.4)mU/L], higher homeostasis model assessment for insulin resistance (HOMA-IR)[2.40(1.49, 3.47) vs. 1.82(1.28, 2.71)], and triglyceride [2.62(2.04, 3.31)mmol/L vs. 2.18(1.81, 2.81)mmol/L], all with significant differences (all P 0.05). Conclusions The body weight gain is higher in the pregnant women with abnormal glucose metabolism than in those with normal glucose metabolism in the first and second trimesters. Large increment of body weight is likely to be a risk factor for abnormal gestational glucose metabolism. Key words: Gestational diabetes mellitus; Gestational weight gain; Body mass index

Association between Adiponectin Receptor 1 Gene Polymorphism and Insulin Resistance in Chinese Patients with Polycystic Ovary Syndrome

Background/Aims: Adiponectin receptor 1 (ADIPOR1) is an identified receptor for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. The ADIPOR1 gene is a potential candidate gene in polycystic ovary syndrome (PCOS). The aim of this study is to assess the association between single-nucleotide polymorphism (SNP) rs1539355 in the ADIPOR1 gene and PCOS in Chinese women. Methods: 302 patients with PCOS and 312 healthy controls were included in this study. The ADIPOR1 genotype distribution was detected using the polymerase chain reaction melting temperature shift method. Results: The genotypic distributions of SNP rs1539355 did not differ in patients with PCOS compared to controls. However, the frequency of the G allele in the PCOS group was significantly higher than that in the control group (p = 0.037). Patients with the AG or GG genotype had a higher homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05) compared to patients with the AA genotype. The fasting insulin levels in subjects with the GG genotype were significantly higher than those in patients with the AA genotype (p < 0.05). Conclusion: SNP rs1539355 in the ADIPOR1 gene is associated with insulin resistance in Chinese PCOS patients.