Higher Homeostatic Model Assessment Of Insulin Resistance Research Articles

Proposal for a new cut-off point for waist-to-hip ratio in women with severe obesity: A cross-sectional study

Obesity is a chronic disease that increases the risk of cardiovascular diseases (CVD), including systemic arterial hypertension (SAH), underestimated in this population. The high mortality related to CVD reveals the need for early screening. One of the training tools is the waist-to-hip ratio (WHR). However, few studies evaluate its relationship with metabolic changes in severe obesity, making necessary a new cut-off point. Cross-sectional study with 75 Brazilian women with severe obesity (mean age: 37,6 years; weight of 122kg and body mass index (BMI) of 47,8kg/m2). Height, weight, neck circumference (NC), hip (HC), waist (WC) and waist-to-hip ratio (WHR) were obtained. Blood samples were collected for lipid/glucose profile. The Receiver Operating Characteristic (ROC) was explored to define cut-off points for WHR based on SAH. Women were compared using the t-Student/Mann Whitney test. Pearson/Spearman correlations were performed, and the significance level was set at 5%. The ROC curve indicated that WHR ≥0.92 best predicted SAH. The group with WHR ≥0.92 had higher Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (p=0.037), insulin (p=0.037), NC (p=0.004), and Atherogenic Index of Plasma (AIP) (p=0.038). WHR correlated with NC (p=0.002; r=0.358), glucose (p=0.026; r=0.270); insulin (p=0.05; r=0.238); HOMA-IR (p=0.01; r=0.3238), triglycerides (p=0.006; r=329) and AIP (p=0.02; r=0.370). A new cut-off point for WHR related to SAH in severe obesity is suggested.

Altered Glucagon and GLP-1 Responses to Oral Glucose in Children and Adolescents With Obesity and Insulin Resistance.

Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion. To examine whether fasting and stimulated glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW). 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n = 22), OIS (n = 22), and NW (n = 36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated. Fasting concentrations of glucagon and GLP-1 were higher in the OIR group, with no significant differences for GIP. The OIR group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences in GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI. Children and adolescents with OIR have elevated fasting concentrations of glucagon and GLP-1, higher glucagon and lower GLP-1 responses during an OGTT compared to those with OIS and NW. In contrast, individuals with OIS have similar hormone responses to those with NW.

Association between cardiorespiratory fitness level and insulin resistance in adolescents with various obesity categories.

An association between cardiorespiratory fitness (CRF) and insulin resistance in obese adolescents, especially in those with various obesity categories, has not been systematically studied. There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents, despite their continuous rise. To investigate the association between CRF and insulin resistance in obese adolescents, with special emphasis on severely obese adolescents. We performed a prospective, cross-sectional study that included 200 pubertal adolescents, 10 years to 18 years of age, who were referred to a tertiary care center due to obesity. According to body mass index (BMI), adolescents were classified as mildly obese (BMI 100% to 120% of the 95th percentile for age and sex) or severely obese (BMI ≥ 120% of the 95th percentile for age and sex or ≥ 35 kg/m2, whichever was lower). Participant body composition was assessed by bioelectrical impedance analysis. A homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Maximal oxygen uptake (VO2max) was determined from submaximal treadmill exercise test. CRF was expressed as VO2max scaled by total body weight (TBW) (mL/min/kg TBW) or by fat free mass (FFM) (mL/min/kg FFM), and then categorized as poor, intermediate, or good, according to VO2max terciles. Data were analyzed by statistical software package SPSS (IBM SPSS Statistics for Windows, Version 24.0). P < 0.05 was considered statistically significant. A weak negative correlation between CRF and HOMA-IR was found [Spearman's rank correlation coefficient (rs) = -0.28, P < 0.01 for CRFTBW; (rs) = -0.21, P < 0.01 for CRFFFM]. One-way analysis of variance (ANOVA) revealed a significant main effect of CRF on HOMA-IR [F(2200) = 6.840, P = 0.001 for CRFTBW; F(2200) = 3.883, P = 0.022 for CRFFFM]. Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF (P = 0.001 for CRFTBW; P = 0.018 for CRFFFM). Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR [F(2200) = 3.292, P = 0.039 for CRFTBW]. Severely obese adolescents had higher HOMA-IR than those who were mildly obese, with either good or poor CRF. However, HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF. CRF is an important determinant of insulin resistance in obese adolescents, regardless of obesity category. Therefore, CRF assessment should be a part of diagnostic procedure, and its improvement should be a therapeutic goal.

Gut microbiome and stages of diabetes in middle-aged adults: CARDIA microbiome study

BackgroundAnimal and human studies suggest the gut microbiome is linked to diabetes but additional data are needed on the associations of the gut microbiome to specific diabetes characteristics. The aim of this study was to examine the associations of gut microbiome composition to insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], duration of diabetes, and 4 stages of diabetes [normoglycemia, pre-diabetes, and diabetes with (+) and without (−) medication for diabetes].MethodsData are from a sub-sample (n = 605) of Black and White participants from the 30-year follow-up exam of the prospectively followed community-based Coronary Artery Risk Development in Young Adults cohort (2015–2016; aged 48–60 years). Stool samples were collected and sequenced using the 16S ribosomal RNA method. Microbial measures included: α diversity (within-person), β diversity (between-person), and taxonomies. All analyses were adjusted for demographic, clinical, lifestyle factors, and use of relevant medications (full adjustment). Multivariate linear regression models were used to assess the association of diabetes characteristics with α diversity and genera abundance, while the association with β diversity was analyzed using permutational multivariate analysis of variance. Statistical significance was set to p-value < 0.05 for α and β diversity analyses and to q-value < 0.1 for genera abundance analyses.ResultsThere were 16.7% of participants with pre-diabetes, and 14.4% with diabetes (9% diabetes+) with median (interquartile range) diabetes duration of 5 (5–10) years. In the fully adjusted models, compared to those with no diabetes, longer diabetes duration and the diabetes + group had a lower α diversity. There were significant differences in β diversity across diabetes-related characteristics. A significantly reduced abundance of butyrate-producing genera was associated with higher HOMA-IR (ex., Anaerostipes and Lachnospiraceae_UCG.004), longer diabetes duration (ex., Agathobacter and Ruminococcus), and diabetes + (ex., Faecalibacterium and Romboutsia).ConclusionsOur results suggest that an adverse alteration of gut microbiome composition is related to higher insulin resistance, longer diabetes duration, and is present in those persons with diabetes using medications. These diabetes-related characteristics were also associated with lower levels of certain butyrate-producing bacteria that produce health-promoting short‐chain fatty acids. Understanding the role of gut microbiota in glucose regulation may provide new strategies to reduce the burden of diabetes.

Effect of excess weight and insulin resistance on DNA methylation in prepubertal children

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population.

Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice

Vast amounts of plastic materials are produced in the modern world and despite recycling efforts, large amounts are disposed in water systems and landfills. Under these storage conditions, physical weathering and photochemical processes break down these materials into smaller particles of the micro- and nano-scale. In addition, ecosystems can be contaminated with plastic particles which are manufactured in these size ranges for commercial purposes. Independent of source, microplastics are abundant in the environment and have found their way into water supplies and the food cycle where human exposure is inevitable. Nevertheless, the health consequences of microplastic ingestion, inhalation, or absorption are largely unknown. In this study we sought to determine if ingestion of microplastics promoted pre-clinical cardiovascular disease (CVD). To do this, we supplied mice with normal drinking water or that supplemented with polystyrene beads of two different sizes (0.5 µm and 5 µm) and two different doses (0.1 μg/ml and 1 μg/ml) each for 12 weeks and measured several indices of metabolism and glucose homeostasis. As early as 3 weeks of consumption, we observed an accelerated weight gain with a corresponding increase in body fat for some exposure groups versus the control mice. Some exposure groups demonstrated increased levels of fasting plasma glucose. Those mice consuming the smaller sized beads (0.5 µm) at the higher dose (1 μg/ml), had increased levels of fasting plasma insulin and higher homeostatic model assessment of insulin resistance (HOMA-IR) scores as well. This was accompanied by changes in the gut microbiome consistent with an obese phenotype. Using samples of perivascular adipose tissue collected from the same group, we observed changes in gene expression consistent with increased adipogenesis. These results suggest that ingestion of polystyrene beads promotes a cardiometabolic disease phenotype and thus may be an unrecognized risk factor for CVD.

Metabolically Healthy Obesity (MHO) vs. Metabolically Unhealthy Obesity (MUO) Phenotypes in PCOS: Association with Endocrine-Metabolic Profile, Adherence to the Mediterranean Diet, and Body Composition.

Obesity and obesity-related low-grade inflammation are common findings in polycystic ovary syndrome (PCOS), the most common endocrine-metabolic disorder-affecting women in reproductive age. The terms metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) have been introduced to define individuals with obesity in whom cardio-metabolic risk factors are absent or present, respectively. To date, evidence investigating differences in body composition and adherence to the Mediterranean diet (MD) between MHO and MUO-PCOS women are lacking. Aim of this study was to better characterize the determinants of the metabolic health status in PCOS patients with obesity according to MHO and MUO phenotypes by evaluating endocrine-metabolic profile, inflammatory status, adherence to the MD, and body composition. The study population consisted of 94 treatment-naïve women with PCOS and obesity (BMI = 38.23 ± 6.62 kg/m2 and age = 24.12 ± 3.68 years). Compared PCOS MHO with PCOS MUO patients, the latter had higher levels of high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), testosterone (p < 0.001), and insulin (p < 0.001), worse metabolic parameters, and higher Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI), and Fatty liver Index (FLI) (p < 0.001). Furthermore, PCOS MUO patients had lower adherence to the MD (p < 0.001) in spite of the same total energy intake (p = 0.102) as compared to PCOS MHO. The presence of MUO was associated with highest hs-CRP levels (OR = 1.49, p < 0.001), more severe hyperandrogenism and cardio-metabolic indices (p < 0.001). On the contrary, being PCOS MUO was associated with lower adherence to the MD (OR = 0.28, p < 0.001), and smaller PhAs (OR = 0.04, p < 0.001). Using a regression linear analysis model PREDIMED score entered at the first step (p < 0.001), followed by VAI (p < 0.001), and FLI (p = 0.032) in this analysis. At ROC analysis, a PREDIMED score of ≤4 (p < 0.001, AUC 0.926) could serve as a threshold for a significantly increased risk of presence the MUO-PCOS phenotype. To the best of our knowledge, this is the first study that characterized MHO and MUO-PCOS women on the basis of their adherence to the MD, body composition, and cardio-metabolic indices, providing evidence of the usefulness of adjunctive diagnostic parameters to better differentiate the MHO/MHO phenotypes in this cohort of PCOS patients with obesity.

Clinical Study of the Impact of ACE I/D Gene Variation on the Clinical Parameters of Patients with Polycystic Ovary Syndrome

To investigate the relationship between angiotensin Ⅰ-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the genetic risks for polycystic ovary syndrome (PCOS) and to evaluate the impact of ACE I/D genotypes on clinical, hormonal, metabolic and oxidative stress parameters in patients with PCOS. This was a retrospective case-control study involving a total of 1 020 PCOS patients and 825 female controls who visited the outpatient clinic of the Department of Reproductive Endocrinology, West China Second Hospital of Sichuan University between 2006 and 2019. The ages of the subjects ranged between 17 and 44. The ACE I/D genotypes were determined by polymerase chain reaction (PCR) and gel electrophoresis. 667 PCOS patients and 527 controls were selected for an analysis of their genotypes and the hormonal, metabolic and oxidative stress parameters. The genotype distributions of the ACE I/D single nucleotide polymorphism was in Hardy-Weinberg equilibrium in both the PCOS group and the control group (all P>0.05), which was representative of the population. There were no statistically significant differences in genotype and allele frequencies between the PCOS and the control groups ( P>0.05). After adjusting for both age and body mass index (BMI), there was no statistically significant difference in clinical characteristics among all genotypes in either the PCOS group or the control group. In the PCOS group, compared with the II genotype subgroup, the ID genotype subgroup had lower luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, while the DD genotype subgroup had higher homeostatic model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA) levels. Compared with the ID genotype subgroup, the DD genotype subgroup had lower serum sex hormone binding globulin (SHBG) level, but higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels ( P<0.05). In the control group, II genotype subgroup had a higher level of total oxidant status (TOS) than that of the DD genotype subgroup. ACE I/D genetic polymorphism is not associated with risks for PCOS. The I/D variation of ACE gene may be related to insulin resistance, dyslipidaemia, hyperandrogenemia and oxidative stress in PCOS patients.

Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity

Previous studies have indicated that gut microbiome may be associated with development of type 2 diabetes. However, these studies are limited by small sample size and insufficient for confounding. Furthermore, which specific taxa play a role in the development of type 2 diabetes remains unclear. To examine associations of gut microbiome composition with insulin resistance and type 2 diabetes in a large population-based setting controlling for various sociodemographic and lifestyle factors. This cross-sectional analysis included 2166 participants from 2 Dutch population-based prospective cohorts: the Rotterdam Study and the LifeLines-DEEP study. The 16S ribosomal RNA method was used to measure microbiome composition in stool samples collected between January 1, 2012, and December 31, 2013. The α diversity (Shannon, richness, and Inverse Simpson indexes), β diversity (Bray-Curtis dissimilarity matrix), and taxa (from domain to genus level) were identified to reflect gut microbiome composition. Associations among α diversity, β diversity, and taxa with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and with type 2 diabetes were examined. Glucose and insulin were measured to calculate the HOMA-IR. Type 2 diabetes cases were identified based on glucose levels and medical records from January 2012 to December 2013. Analyses were adjusted for technical covariates, lifestyle, sociodemographic, and medical factors. Data analysis was performed from January 1, 2018, to December 31, 2020. There were 2166 participants in this study: 1418 from the Rotterdam Study (mean [SD] age, 62.4 [5.9] years; 815 [57.5%] male) and 748 from the LifeLines-DEEP study (mean [SD] age, 44.7 [13.4] years; 431 [57.6%] male); from this total, 193 type 2 diabetes cases were identified. Lower microbiome Shannon index and richness were associated with higher HOMA-IR (eg, Shannon index, -0.06; 95% CI, -0.10 to -0.02), and patients with type 2 diabetes had a lower richness than participants without diabetes (odds ratio [OR], 0.93; 95% CI, 0.88-0.99). The β diversity (Bray-Curtis dissimilarity matrix) was associated with insulin resistance (R2 = 0.004, P = .001 in the Rotterdam Study and R2 = 0.005, P = .002 in the LifeLines-DEEP study). A total of 12 groups of bacteria were associated with HOMA-IR or type 2 diabetes. Specifically, a higher abundance of Christensenellaceae (β = -0.08; 95% CI, -0.12 to -0.03: P < .001), Christensenellaceae R7 group (β = -0.07; 95% CI, -0.12 to -0.03; P < .001), Marvinbryantia (β = -0.07; 95% CI, -0.11 to -0.03; P < .001), Ruminococcaceae UCG005 (β = -0.09; 95% CI, -0.13 to -0.05; P < .001), Ruminococcaceae UCG008 (β = -0.07; 95% CI, -0.11 to -0.03; P < .001), Ruminococcaceae UCG010 (β = -0.08; 95% CI, -0.12 to -0.04; P < .001), or Ruminococcaceae NK4A214 group (β = -0.09; 95% CI, -0.13 to -0.05; P < .001) was associated with lower HOMA-IR. A higher abundance of Clostridiaceae 1 (OR, 0.51; 95% CI, 0.41-0.65; P < .001), Peptostreptococcaceae (OR, 0.56; 95% CI, 0.45-0.70; P < .001), C sensu stricto 1 (OR, 0.51; 95% CI, 0.40-0.65; P < .001), Intestinibacter (OR, 0.60; 95% CI, 0.48-0.76; P < .001), or Romboutsia (OR, 0.55; 95% CI, 0.44-0.70; P < .001) was associated with less type 2 diabetes. These bacteria are all known to produce butyrate. In this cross-sectional study, higher microbiome α diversity, along with more butyrate-producing gut bacteria, was associated with less type 2 diabetes and with lower insulin resistance among individuals without diabetes. These findings could help provide insight into the etiology, pathogenesis, and treatment of type 2 diabetes.

Adipokines, Weight Gain and Metabolic and Inflammatory Markers After Antiretroviral Therapy Initiation: AIDS Clinical Trials Group (ACTG) A5260s.

The adipokines leptin and adiponectin, produced primarily by adipose tissue, have diverse endocrine and immunologic effects, and circulating levels reflect adipocyte lipid content, local inflammation, and tissue composition. We assessed relationships between changes in regional fat depots, leptin and adiponectin levels, and metabolic and inflammatory markers over 96 weeks in the AIDS Clinical Trials Group (ACTG) A5260s metabolic substudy of the A5257 randomized trial of tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir among treatment-naive persons with human immunodeficiency virus (PWH). Fat depots were measured using dual-energy absorptiometry and abdominal computed tomographic imaging at treatment initiation and 96 weeks later. Serum leptin and adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP) were measured at the same timepoints. Multivariable regression models assessed relationships between fat depots, adipokines, HOMA-IR, and hsCRP at week 96. Two hundred thirty-four participants maintained viral suppression through 96 weeks (90% male, 29% black, median age 36 years). Serum leptin increased over 96 weeks (mean change 22%) while adiponectin did not (mean change 1%), which did not differ by study arm. Greater trunk, limb, and abdominal subcutaneous and visceral fat were associated with higher HOMA-IR and hsCRP at 96 weeks, but serum leptin level was a stronger determinant of these endpoints using a mediation model approach. A similar mediating effect was not observed for adiponectin. Higher circulating leptin is associated with greater HOMA-IR and hsCRP independent of fat depot size, suggesting that greater adipocyte lipid content may contribute to impaired glucose tolerance and systemic inflammation among PWH starting antiretroviral therapy.

Index of Cardiac Age Index and Cardiometabolic Biomarkers in Adults with Metabolic Syndrome.

Background: The presence of metabolic syndrome (MetS) seems to alter or accelerate the aging process of tissues or organs including the heart. We aim to investigate whether MetS are associated with an index of cardiac age calculated by parameters derived from 128-slice cardiac multidetector computed tomography (MDCT) and cardiometabolic biomarkers in adults. Materials and Methods: In this cross-sectional study, the data were collected from 135 subjects who underwent a comprehensive health checkup, including cardiac MDCT in adults (age ≥18 years). Cardiometabolic biomarkers and an index of cardiac age were measured. Results: Sixty-one (45.2%) had MetS and 44 subjects (32.6%) presented with moderate or severe coronary artery stenosis (CAS) on cardiac MDCT. MetS had positive correlations with several anthropometric variables, metabolic variables [triglyceride, gamma-glutamyl transpeptidase (GGT), homeostatic model assessment of insulin resistance (HOMA-IR)], and systolic blood pressure, cardiac parameters, an index of cardiac age and CAS, whereas had a negative correlation with high-density lipoprotein cholesterol. The diagnostic accuracy for MetS had similar area under the curve among the four variables (index of cardiac age, CAS, HOMA-IR, GGT). On age-adjusted multivariate analysis, only high index of cardiac age (≥55.0 years), and high HOMA-IR (≥1.22) were significantly and independently associated with MetS [odds ratio (OR) 2.48, 95% confidence interval (CI) 1.19-5.18, P = 0.016 and OR 3.41, 95% CI 1.65-7.06, P = 0.001, respectively]. Conclusion: Adults with MetS had higher index of cardiac age and higher HOMA-IR, compared with adults without MetS.

Long-term particulate matter 2.5 exposure, insulin resistance and type 2 diabetes risk in Mexican adults: results from GEA study.

Background/Aim. Type two diabetes mellitus (T2DM) is a leading cause of morbidity and mortality in Mexico. The aim of this study was to examine associations between particulate matter 2.5 (PM2.5) exposure and T2DM risk.Methods. This study comprised 1478 individuals belonging to the Genetics of Atherosclerotic Mexican Study (GEA) in Mexico City. Type 2 diabetes mellitus was defined by the American Diabetes Association criteria and insulin resistance (IR) was considered when the HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) values were more than 75 percentile. PM2.5 concentrations for long-term periods (1 to 9 years) were assigned by inverse distance weighted (IDW) of data from air quality monitors. Linear regression models or logistic regression models were employed to assess long-term PM2.5 exposure and continuous variables (HOMA-IR or glycosylated hemoglobin [Hb1Ac]) or binary outcomes (T2DM or IR ), respectively. All models were adjusted for age, sex, body mass index, socioeconomic status, marital status, smoking, physical activity and total calories intake. Results. The prevalence of T2DM was 13.2% and for IR was 57.9%. PM2.5 exposure at year 1, 3, and 5 years before the baseline visit were significantly associated with higher HOMA-IR and IR. Each 10 ug/m3 of PM2.5 at year 1 was associated with 16% (95% CI: 1.01-1.33) higher odds of IR, and year 5 with 20% (95%CI: 1.05-1.36) higher odds of IR. Each 10 ug/m3 PM2.5 increased at year 2 (0.4% [95% CI: 0.04-0.74]) and 7 (0.5% [95% CI: 0.14-0.80]) were associated with increased HbA1c. Finally, no significant associations were observed between PM2.5 exposure at any time point and type 2 diabetes mellitus risk. Conclusions. The association between long-term exposure to PM2.5 and insulin resistance is relevant in the context of high obesity rate and poor glycemic control characteristic of Mexican adults.

Association between relative fat mass, uric acid, and insulin resistance in children with chronic kidney disease.

This cross-sectional study investigates the association between insulin resistance (IR) and serum uric acid (sUA) and relative fat (RFM) and lean mass (RLM) profiles in children with chronic kidney disease (CKD). RLM and RFM were assessed by bioimpedance spectroscopy in 41 children and adolescents. Normal weight obesity (NWO) was defined as normal height-age body mass index and RFM >85th percentile, according to age and sex. Homeostatic model assessment of insulin resistance (HOMA-IR) level >95th percentile, according to sex and pubertal stage, and sUA >7mg/dl were used to define IR and hyperuricemia, respectively. High RFM (15 patients) and NWO (7 patients) were associated with higher HOMA-IR in total (p < 0.001) and normal-weight patients (p = 0.004), respectively. RFM was positively and RLM negatively correlated to HOMA-IR (rs = 0.500, p = 0.001 and rs = -0.539, p < 0.001, respectively) and sUA (rs = 0.370, p = 0.017 and rs = -0.325, p = 0.038, respectively), while sUA was positively correlated to HOMA-IR (rs = 0.337, p = 0.031). Hyperuricemia (16 patients) was positively associated with higher RFM and HOMA-IR (p = 0.001 and p = 0.010, respectively). The correlation between sUA and HOMA-IR lost significance after adjustment for RFM. In logistic regression analysis, a 5% increase in RFM was associated with IR (11 patients) independently of the age, sex, sUA, and CKD stage in both total (OR 2.174, 95% CI 1.115-4.225) and normal-weight (OR 3.504, 95% CI 1.110-11.123) patients. Children with high RFM, including those presenting NWO, are at risk for IR regardless of CKD stage. RFM is probably the mediator of the link between sUA and IR.

P0894OBESITY IMPAIRS THE ACUTE RESPONSE TO AN ORAL PHOSPHATE CHALLENGE

Abstract Background and Aims T Obesity is an increasing health problem world-wide. People who are overweight or obese are at greater risk of developing chronic diseases including cardiovascular disease (CVD). Factors associated with dysregulated phosphate metabolism have been linked to the presence of vascular calcification in people with type 2 diabetes (T2D) with normal kidney function. Insulin resistance and abdominal obesity are associated with increased circulating levels of phosphaturic hormones including fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH). Abnormalities in phosphate regulation may not be reflected in single circulating measurements of serum phosphate, but can be revealed by the acute circulating and mineral response to an oral challenge of phosphate. The aim of this study was to determine if obesity and insulin resistance impact the acute capacity to excrete an oral phosphate challenge. Method Community-dwelling people (N=78) free of T2D and symptomatic CVD (∼10 males and ∼10 females from each decade between 40 and 80 years) with normal kidney function were recruited from Kingston, Ontario, Canada. Following a 12-hour fast, participants consumed a 1250 mg phosphate drink (sodium phosphate) where blood and urine were collected at baseline, 1, 2 and 3 hours following the oral challenge. Participants with a high-risk metabolic profile characterized by an elevated waist-to-height ratio (WHtR) (&amp;gt; 0.58) were matched by age and sex to participants with a low risk WHtR (&amp;lt;0.5). Results The results reveal a significant impact of obesity on phosphate excretion in response to an oral phosphate challenge. There was an association between WHtR ratio and the level of iFGF-23 (R=-0.34 p&amp;lt;0.01) but not PTH. After adjustment for age and sex, WHtR ratio was inversely correlated with urinary phosphate excretion in response to the phosphate challenge (R=-0.29, p=0.02) and the change in fractional excretion of phosphate (r=-0.34, p=0.007). From the larger cohort, an age- and sex- matched subset was selected for 12 high risk and 12 low risk metabolic profiles with WHtR of 0.66±0.02 and 0.46±0.01, respectively. Kidney function was the same between the two groups (eGFR 92.3±13.1 versus 95.8±13.6 ml/min/1.73m2 respectively) but high risk participants had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) (1.61±0.81 versus 0.68±0.3, p&amp;lt;0.01). Participants with a high risk metabolic profile had a greater increase in serum phosphate from baseline (29% increase in the area under the curve, p=0.04) and a significantly blunted increase in the fractional excretion of phosphate in response to the oral phosphate challenge (35% reduction in area under the curve [AUC], p=0.03) compared to the matched low risk profile participants. Conclusion Overweight/obese individuals demonstrate impaired response to an oral phosphate challenge, whereby phosphate excretion was impaired and there was increased exposure to new circulating phosphate. An impaired acute phosphate response may contribute to the initiation or propagation of vascular calcification. Dysregulated phosphate homeostasis may be an under-recognized cardiovascular risk factor in obese people that could be modified by diet and weight loss. Whether insulin enhances renal phosphate reabsorption requires further study.

SUN-LB103 The Relationship Between Alcohol Consumption Patterns and Insulin Sensitivity in Obesity

BACKGROUNDThe effects of alcohol intake on insulin sensitivity have produced conflicting results with both beneficial and adverse effects observed. This study aimed to compare the relationship between patterns of alcohol consumption and insulin sensitivity in obese Veterans. METHODSWe performed a cross-sectional study of obese (BMI 30.0-45.0 kg/m2), nondiabetic U.S. Military Veterans without active mental health diagnoses, including no report of dependent alcohol use within the last 12 months. Alcohol exposure over the previous 12 months (mos) was assessed using a study-developed questionnaire and Michigan Alcoholism Screening Test (MAST). Fasting insulin, glucose, and a 75gm OGTT were completed to determine Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and prediabetes (preDM) score of 0, 1, or 2 based on fulfilling 0, 1, or at least 2 of the ADA criteria for preDM, respectively. Linear regression was used to assess for associations between measures of insulin resistance and alcohol consumption; unstandardized β and p-value are reported for variable of interest. RESULTS104 Veterans participated (66% males; 44±8years (range: 25-60); BMI 36±4kg/m2 (range: 29-45); 53% White, 46% African American, 2% Alaskan/Native American, 1% Other). 83 participants reported any alcohol intake in the previous 12 mos and neither preDM score (p=0.57) nor HOMA-IR (p=0.14) were predicted by this question. PreDM score groups were similar in gender, BMI, and weight, but age predicted both preDM score (r2=0.09, β=0.025, p=0.006) and HOMA-IR (r2=0.05, β=-0.09, p=0.034); therefore, all regressions were adjusted for age. There was a negative association between the number of days of alcohol intake with HOMA-IR (β=-0.271, p=0.037) but no association occurred with preDM score (p=0.15). Fewer days of binge drinking was associated with higher HOMA-IR (β= -0.342, p=0.058) and preDM score (β=-0.075, p=0.05). There was no significant association between total quantity of alcohol intake and HOMA-IR (p=0.13) nor preDM score (p=0.15). There was no association between MAST score and HOMA-IR (p=0.7) or preDM score (p=0.3). CONCLUSIONIn our cohort of obese, non-alcohol dependent Veterans, the reported number of days of alcohol intake and days of binge drinking in the previous 12 mos were lower in those with markers of insulin resistance. These results suggest that drinking patterns among obese patients may have unique effects on insulin sensitivity that warrant further investigation.

INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1, NON-ALCOHOLIC FATTY LIVER DISEASE, AND ITS RELATIONSHIP WITH FRUCTOSE CONSUMPTION IN CHILDREN WITH OBESITY.

Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = -0.25; p = 0.03), body mass index (BMI) (r=-0.42; p = 0.02), and HOMA-IR (r=-0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

The Association of Subclinical Insulin Resistance with Thyroid Autoimmunity in Euthyroid Individuals

SUMMARYHashimoto thyroiditis is characterized by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies that gradually lead to thyroid cell destruction. As hypothyroidism has been associated with insulin resistance (IR), we aimed to investigate whether IR is associated with thyroid antibody presence and whether the degree of IR correlates with their concentration in euthyroid individuals. A total of 164 non-diabetic, euthyroid individuals, average age 34 years, were included in the study, divided into two groups according to Hashimoto thyroiditis and underwent 5-hour oral glucose tolerance test. The degree of IR was evaluated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The Hashimoto thyroiditis group had higher HOMA-IR (p=0.003) and lower glucose levels (p=0.04). HOMA-IR correlated positively with anti-TPO (p<0.001). Linear logistic regression revealed that anti-TPO concentration increased by 18.13 (p=0.001) with each HOMA-IR unit. IR might trigger thyroid antibody production and Hashimoto thyroiditis development, which needs to be evaluated in further larger scale follow up studies.

ADIPOR2 variant is associated with higher fasting glucose level in non-diabetic Chinese Han population

A high but normal fasting plasma glucose level in adults is a marker for insulin resistance and future development of type 2 diabetes mellitus. We aimed to investigate whether ADIPOR2 variants are associated with increased fasting plasma glucose (FPG) in non-diabetic Chinese Han subjects who had normal FPG levels. This study included 2038 subjects among the non-diabetic Chinese Han population. The ADIPOR2 polymorphisms were genotyped by the TaqMan method. For the analysis, participants were divided into low-normal FPG group (FPG FPG ≥ 4.88 mmol/L). We identified five single nucleotide polymorphisms (SNPs) of ADIPOR2 gene: rs10773989, rs2370055, rs9300298, rs10773983, and rs13611594. There was no significant difference in FPG levels between different genotypes of rs10773989, rs2370055, rs9300298, and rs13611594. Our data showed a significant association of rs10773983 with higher FPG levels, fasting insulin levels, and homeostatic model assessment of insulin resistance (HOMA-IR) in A-allele carriers (p = 0.006, p < 0.001, and p < 0.001, respectively). The subjects in high FPG group had higher median fasting insulin level (9.25 vs 8.16 μIU/mL, p = 0.003) and higher HOMA-IR (2.21 vs 1.58, p < 0.001) than those in normal FPG group. Subjects with the A-allele of rs10773983 compared to subjects with G-allele had 1.222-fold higher risk for high-normal FPG (OR = 1.222, 95%CI = 1.010–1.478, p = 0.039). Our findings suggest that ADIPOR2 rs10773983 polymorphism may be associated with an increased risk of high-normal FPG among non-diabetic Chinese Han subjects who have normal FPG levels.

Association of Low Urine pH with Insulin Resistance in Non-Diabetic Japanese Subjects.

Epidemiology studies have revealed that patients with obesity, hyperglycemia, or hypertension are associated with a decreased urine pH. These metabolic disorders are related to insulin resistance; however, the association between urine pH and insulin resistance remains unclear. To evaluate this association while controlling for covariates, the present study was conducted in 1084 non-diabetic Japanese subjects undergoing health examination. Fasting urine pH was analyzed using an automated urine dipstick analyzer. The subjects were divided into five groups according to urine pH: those with pH <5.5, 5.5, 6.0, 6.5, and >6.5. Insulin resistance was determined using the homeostatic model assessment of insulin resistance (HOMA-IR) and divided into three categories: lower, middle, and higher tertiles of HOMA-IR. Analysis of covariance and multivariate logistic regression analysis were used to control confounding factors including serum uric acid. Analysis of covariance showed an increase in the mean HOMA-IR from 1.26, 1.46, 1.69, and 1.75 to 1.89 with a decrease in urine pH (p<0.001). Subjects with urine pH ≤5.5 had a significantly higher HOMA-IR than those with urine pH>6.5. Furthermore, multivariate logistic regression analysis showed that urine pH had an inverse and independent association with HOMA-IR. In subjects with urine pH 5.5 and <5.5, adjusted odds ratio (95% confidence interval) for the incidence of higher tertile of HOMA-IR was 1.34 (1.04-1.73) and 1.52 (1.09-2.13), respectively (reference, subjects with a urine pH>6.5). Insulin resistance is independently associated with a lower urine pH, possibly via lower formation of ammonium in the kidneys.

Effects of insulin resistance on the association between the circulating retinol-binding protein 4 level and clustering of pediatric cardiometabolic risk factors.

Retinol-binding protein 4 (RBP4) and insulin resistance (IR) are clinical parameters associated with cardiometabolic diseases. The mediating and modifying roles of IR on children's susceptibility to cardiometabolic disorders are undetermined. This study investigated the mediating and modifying effects of the homeostatic model assessment of IR (HOMA-IR) on the relationship between the serum RBP4 level and clustering of pediatric cardiometabolic risk factors. We assessed the diet, physical activity, cardiometabolic risk factors, and clinical parameters of 272 randomly selected adolescents from a large-scale cross-sectional study (n = 2727). Two HOMA-IRs (HOMA1-IR and HOMA2-IR) were used to evaluate the designated effects. Levels of serum RBP4 positively correlated with the levels of the 2 HOMA-based-IRs, and HOMA-IR correlated to all components of pediatric metabolic syndrome (MetS), the number of abnormal components, and a body-weight-weighted principal component score extracted from 12 cardiometabolic risk factors. Increased RBP4 levels had positive effects on waist circumference (WC), triglyceride, and the number of abnormal MetS components (0.310 cm, 1.384 μg/dL, and 0.021 item elevations, respectively), and the HOMA-IRs explained 17.7% to 21.9%, 11.8% to 27.6%, and 23.8% to 25.0% of these effects. The association of WC and the number of abnormal MetS components with the serum RBP4 level was enhanced by higher HOMA-IR (β for interaction, 0.13 and 0.01 for HOMA1-IR, and 0.32 and 0.02 for HOMA2-IR, respectively). HOMA-IR is associated with the circulating RBP4 level and cardiometabolic risk factors in adolescents. Pediatric HOMA-IR may have mediating and modifying effects on the positive correlations between RBP4 and the clustering of MetS components.