Model Assessment Insulin Resistance Index Research Articles

Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau

Several environmental factors including hypoxia have been reported to contribute to oxidative stress in individuals living in the highlands. However, little is known about the role of oxidized low-density lipoprotein (ox-LDL) among community-dwelling elderly in the Qinghai-Tibet plateau. The study population comprised 168 community-dwelling elderly subjects aged 60 years or older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan County, located 3000 to 3200 m above sea level, 30 km northwest of Xining, Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody-based enzyme-linked immunosorbent assay. Mean ox-LDL level was higher among Tibetan elderly than Han elderly (Tibetan, 79.0 ± 29.6 U/L; Han, 62.8 ± 23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL levels (≥70 U/L) were significantly associated with a homeostasis model assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after adjusting for age, sex, and ethnicity. Our findings support the hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders compared with those among Han elderly. As ox-LDL levels can affect insulin resistance and arteriosclerosis, further research is needed to determine how oxidative stress influences the health situation among elderly individuals at high altitudes.

Obesity and inflammatory biomarkers in women with polycystic ovary syndrome

ObjectiveTo evaluate the roles of obesity and inflammatory biomarkers associated with medical complications in women with PCOS. Study designRetrospective, BMI-matched study. A total of 330 patients, including 165 women with PCOS and 165 women without PCOS, were evaluated. The insulin resistance (homeostasis model assessment insulin resistance index – HOMA) and lipid profiles were assessed. The adiponectin, leptin, ghrelin, resistin, anti-müllerian hormone (AMH), sex hormone-binding globulin (SHBG), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels were also measured. ResultsWomen with PCOS had significantly higher AMH, fasting insulin, total cholesterol, and low-density lipoprotein levels and lower SHBG levels compared with the controls. There was no difference in the serum obesity and inflammatory biomarkers between the PCOS cases and the controls. After adjusting for BMI and age, IL-6 was positively correlated with HOMA, and SHBG was negatively correlated with HOMA, triglyceride, and LDL. ConclusionsThe serum adipokines levels are not good markers for PCOS. PCOS patients were characterized by their high AMH and low SHBG levels. A low level of SHBG should play an important role in the pathogenesis of the medical complications observed in women with PCOS.Clinical trial registration number NCT01989039.

Relationship Between Insulin Resistance and Mean Platelet Volume in Gestational Diabetes Mellitus.

Objectives:A few studies have investigated the relationship between mean platelet volume (MPV) and gestational diabetes mellitus (GDM), and in these studies the relationship between MPV and insulin resistance has not been analyzed. Our aim in this study was to compare MPV values of the pregnant women with or without GDM and evaluate the relationship between MPV and homeostasis model assessment insulin resistance index (HOMA-IR) in pregnant women.Materials and Methods:One hundred and fourteen with GDM measurements being obtained before any dietary advice or therapy with insulin or hypoglycemic agents were given, and 76 with healthy pregnant women were included the study.Results:In the group with GDM, MPV value was found to be significantly higher than that of the control group (10.2 fl [8.0–12.2] vs. 9.9 fl [5.81–10.9], P = 0.004). HOMA-IR value was detected to be significantly higher in the group with GDM (2.46 [1.5–5.88] vs. 1.30 [0.17–2.92], P < 0.001). A positive correlation between MPV and HOMA-IR was found (r = 0.30, P = 0.002).Conclusion:We have shown that MPV was significantly elevated in GDM patients when compared to healthy pregnant women. Furthermore, we found that there was a positive correlation between MPV and HOMA-IR.

PP.33.18

Objective:Although the visceral fat area (VFA) value and homeostasis model assessment insulin resistance (HOMA-R) index in patients with type 2 diabetes mellitus (DM) or metabolic syndrome (MetS) are known to be higher, the association of VFA and HOMA-R with hypertension (HT) remains unclear. In the

High cardiometabolic risk in healthy Chilean adolescents: associations with anthropometric, biological and lifestyle factors.

To analyse the prevalence of cardiovascular risk factors in healthy adolescents of low to middle socio-economic status and to study the influence of anthropometric, biological and lifestyle factors on the risk of metabolic syndrome (MetS). Cross-sectional study. BMI, waist circumference, blood pressure, fat and lean mass (by dual-energy X-ray absorptiometry), TAG, HDL-cholesterol, glucose, insulin, homeostatic model assessment-insulin resistance index (HOMA-IR), food intake and physical activity were measured. Cardiovascular risk factors were defined using the International Diabetes Federation criteria and insulin resistance using HOMA-IR ≥2.6. Bivariate and multivariate regressions examined the associations between MetS and anthropometric, biological and lifestyle factors. Observational cohort study including Chilean adolescents, who were part of a follow-up study beginning in infancy. Adolescents aged 16-17 years (n 667). In the sample, 16.2% had obesity and 9.5% had MetS. Low HDL-cholesterol (69.9%), abdominal obesity (33.3%) and fasting hyperglycaemia (8.7%) were the most prevalent cardiovascular risk factors. In males, obesity (OR=3.7; 95% CI 1.2, 10.8), insulin resistance (OR=3.0; 95% CI 1.1, 8.2), physical inactivity (OR=2.9; 95% CI 1.1, 7.7) and sarcopenia (OR=21.2; 95% CI 4.2, 107.5) significantly increased the risk of MetS. In females, insulin resistance (OR=4.9; 95% CI 1.9, 12.6) and sarcopenia (OR=3.6; 95% CI 1.1, 11.9) were significantly associated with MetS. High prevalences of obesity, abdominal obesity, dyslipidaemia, fasting hyperglycaemia and MetS were found in healthy adolescents. In both sexes, sarcopenia and insulin resistance were important risk factors of MetS. Promotion of active lifestyles at the school level and regulation of the sale of energy-dense foods are needed.

Examination of the brain natriuretic peptide rs198389 single-nucleotide polymorphism on type 2 diabetes mellitus and related phenotypes in an Algerian population

BackgroundIn European populations, the NPPB rs198389 single nucleotide polymorphism (SNP) is associated with a reduced risk of type 2 diabetes mellitus (T2DM). We investigated the putative associations between NPPB rs198389, the T2DM risk and quantitative metabolic traits in an Algerian population. MethodsThe association analysis was performed as a T2DM case–control study (with 78 cases and 645 controls) nested into the ISOR population-based study. ResultsThe NPPB rs198389 SNP was not associated with T2DM (odds ratio (OR) [95% confidence interval (CI)]=0.73 [0.51–1.04], p=0.08). However, the C allele was associated with lower fasting plasma insulin levels (p=0.05) and a lower homeostatic model assessment insulin resistance index (p=0.05) in non-diabetic individuals. ConclusionThe NPPB rs198389 SNP might modulate fasting insulin levels in an Algerian population.

Levels of F2 isoprostane in Behcet's disease: Correlation with cardiometabolic risk factors

ObjectiveBehcet's disease (BD) is a chronic inflammatory disease and recent findings suggest a role of oxidative stress in the pathogenesis of BD. Free radical-induced oxidative stress is also involved in the pathogenesis of cardiovascular and other rheumatic diseases. Oxidative stress may be detected in vivo by measuring F2 isoprostanes. Here, we measured plasma levels of F2 isoprostane in patients with BD and evaluated the correlation of F2 isoprostane with cardiometabolic risk factors.MethodsForty-three patients with BD in remission and 37 age- and sex-matched controls were recruited for the study. Blood samples were obtained to determine F2 isoprostane, C-reactive protein levels, erythrocyte sedimentation rate, and other biochemical parameters. Homeostasis model assessment insulin resistance and body mass index were calculated. Systolic blood pressure, diastolic blood pressure, and waist circumference were measured.ResultsPlasma F2 isoprostane, fasting plasma glucose, triglyceride, and C-reactive protein levels were significantly higher in patients with BD compared with healthy controls, whereas high-density lipoprotein cholesterol levels were significantly lower in patients with BD. F2 isoprostane levels did not correlate with cardiometabolic risk factors, C-reactive protein levels, or erythrocyte sedimentation rate.ConclusionHigh levels of F2 isoprostane in patients with BD indicate oxidative stress. Antioxidant therapeutic approaches could potentially affect the course of this disease.

Insulin Resistance Increases the Risk of Contrast-Induced Nephropathy in Patients Undergoing Elective Coronary Intervention.

We assessed the influence of insulin resistance (IR) on the development of contrast-induced nephropathy (CIN) in patients (n = 719) undergoing elective percutaneous coronary intervention (PCI). Patients were divided into diabetes mellitus (DM = 242), nondiabetic IR (IR = 120), and nondiabetic insulin sensitivity (IS = 357) groups according to medical history and homeostasis model assessment insulin resistance index. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were measured before and 72 hours after PCI. There were no differences in SCr and eGFR among the groups before PCI; SCr increased and eGFR decreased significantly in the DM and IR groups post-PCI (P < .001). The incidence of CIN in the IR group was as high as in the DM group and were both significantly higher than in the IS group (6.7% vs 8.7% vs 2.2%, P < .05). Multivariate logistic regression analysis showed DM (odds ratio [OR] = 1.19, 95%CI = 1.08-1.510, P < .001), HOMA-IR (OR = 1.39, 95%CI = 1.23-1.58, P < 0.001), and eGFR (OR = 0.88, 95%CI = 0.84-0.92, P < .001) were independent risk factors in predicting CIN. Screening IR patients and taking appropriate prophylactic strategy before PCI may reduce the incidence of CIN.

Relationship between neck circumference and insulin resistance in a community population

Objective To investigate the relationship between neck circumference(NC)and insulin resistance in a large Chinese cohort of community population. Methods A total of 2 318 subjects in this study were from a community-based health examination survey in Xuzhou. Serum triglyceride(TG), total cholesterol(TC), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C), and glucose levels were determined. NC, height, waist circumference(WC), hip circumference, and body weight were measured. Insulin resistance was assessed by homeostasis model assessment-insulin resistance(HOMA-IR)index. Results NC was positively correlated with age, body mass index(BMI), WC, hip circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, uric acid, TC, TG, LDL-C, while negatively correlated with HDL-C. NC was significantly associated with increasing trend of HOMA-IR in both men and women after adjusting for age and other cardiometabolic risk factors. The associations still existed after further adjustment for BMI and WC. Moreover, there were significant interactions between NC and BMI or WC on HOMA-IR(P<0.01). The associations between NC and HOMA-IR appeared stronger among those with higher BMI or WC. Conclusions In healthy Chinese adults, NC is independently related to HOMA-IR and other cardiometabolic risk factors, and interacts with other parameters of overall or central adiposity, such as BMI and WC. (Chin J Endocrinol Metab, 2015, 31: 33-36) Key words: Neck circumference; Insulin resistance

Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring.

Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts.

Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients.

The association of retinol binding protein 4 (RBP4) with atherosclerosis of the carotid artery in type 2 diabetes mellitus (T2DM) remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups: in group I, patients had normal neck vascular ultrasound, in group II, intimal carotid artery media thickness was equal to or more than 1 mm, and in group III, carotid artery plaque was present. Height, weight, blood pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (apoA-1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein (HsCRP) were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbA1c, TG, TC, LDL-C, APOB, Lp(a), HsCRP, RBP4 and homeostasis model assessment insulin resistance index (HOMA-IR) were significantly lower in group I than in the other two groups (P<0.01, P<0.01). Plasma levels of HbA1c, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp(a), waist and BP were significantly increased in group III than in group II (P<0.01). Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclerosis and its risks in descending order were: high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbA1c and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.

Effects of exercises on the lipid metabolism and expression of PPAR-α mRNA in skeletal muscles of ApoE knockout mice

Objective To observe the influence of exercises on the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α) and its target genes of acyl-CoA oxidase (ACO),Enoyl-CoA-hydratase and 3-hydroxyacyl-CoA-dehydrogenase (EHHADH) in the skeletal muscles in insulin-resistance mice to develop a way to improve the lipid metabolism.Methods Twenty male ApoE knockout mice were randomly divided into two groups,the high-fat diet group (group HFD) and the exercise training group (group Ex).The HFD group were fed with highfat diet,while the Ex group were fed in the same way,with additionally swimming training.And ten healthy male C57BL/6j mice were chosen as the control group(group ND).After 12 weeks of intervention,the serum lipid,blood glucose and insulin levels were determined,and homeostasis model assessment insulin resistance index (Homa-IRI) was calculated.The bilateral gastrocnemiuses were cut to be observed under a transmission electron microscope,and the mRNA expression of PPAR-α,ACO and EHHADH in skeletal muscle were measured using reverse transcription polymerase chain reaction(RT-PCR).Results The transmission electron microscope showed that the sarcolemma edema,mitochondrial swelling,as well as focal myocytolysis and edema within myofibrils were observed in the HFD group.The total cholesterol,low-density lipoprotein cholesterol,free fatty acid,fasting glucose,insulin and HomaIRI of the HFD group were significantly higher than the control group (P ＜ 0.05),while the mRNA expression of PPAR-α,ACO and EHHADH was significantly deceased than the latter(P ＜ 0.05).After swimming,the abovementioned pathological changes disappeared.The serum lipid of the Ex group were significantly lower (P ＜ 0.05),while HDL was significantly higher (P ＜ 0.05).And fasting insulin,glucose and HOMA-IR of the Ex group were significantly lower (P ＜ 0.05),while the mRNA expression of the above in the Ex group were significantly increased (P ＜0.05).Conclusion Swimming training could improve insulin resistance and metabolic disorder of lipid of ApoE knockout mice.The possible mechanisms may be through up-regulating the expression of PPAR-α,which in turn stimulates the expression of ACO and EHHADH mRNA to strengthen fatty acid β-oxidation. Key words: Exercises; Insulin resistance; Peroxisome proliferators-activated receptor alpha; acyl-CoA oxidase; Enoyl-CoA-hydratase and 3-hydroxyacyl-CoA-dehydrogenase

Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial

BackgroundNon-alcoholic fatty liver disease is a major health problem worldwide. Resveratrol is a natural polyphenol found in edible plants that has a variety of biochemical and physiological effects. AimsTo evaluate the effect of resveratrol on insulin resistance, glucose and lipid metabolism in non-alcoholic fatty liver disease. MethodsDouble-blind, randomized, placebo-controlled trial: 60 subjects with non-alcoholic fatty liver disease were given 2 placebo capsules (placebo group) or 2 150mg resveratrol capsules (resveratrol group) twice daily for three months. Liver ultrasound imaging, anthropometric profile, serum liver enzymes, insulin, glucose, C-peptide, lipid profile, and inflammation-related cytokines were compared pre and post-treatment. ResultsCompared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol [−6.00 (−9.00, −3.00) IU/L, −0.64±0.31mmol/L, and −0.41±0.35mmol/L, respectively, P≤0.001] alanine aminotransferase, total cholesterol [−7.00 (−11.0, −2.50) IU/L and −0.67±0.50mmol/L, respectively, P=0.002], and homeostasis model assessment insulin resistance index (−0.60±1.15, P=0.016). In the resveratrol group significant reductions of the levels of tumour necrosis factor-alpha, cytokeratin 18 fragment, and fibroblast growth factor 21 [−0.53±1.30pg/mL, −26.9 (−70.3, 5.12) IU/L and −23.3 (−43.0, 0.31) pg/mL, respectively, P<0.05] and elevation of adiponectin level [1.22 (−0.37, 1.60) ng/mL, P=0.025] were observed. ConclusionResveratrol supplementation may benefit patients with non-alcoholic fatty liver disease.

Subclinical hypothyroidism: association with cardiovascular risk factors and components of metabolic syndrome

The aim of this cross-sectional study was to evaluate the cardiovascular risk in patients with subclinical hypothyroidism (SH) and metabolic syndrome (MetS) components. The study included 60 patients with SH and a control group of 60 healthy volunteers, gender and age matched, with normal thyroid-stimulating hormone (TSH) and free thyroxin (FT4) concentration. The following measurements were made in all participants: TSH, FT4, thyroid peroxidase antibodies, anti-thyroglobulin antibodies, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), TC/HDL cholesterol and LDL/HDL cholesterol ratio, basal insulin level and homeostatic model assessment insulin resistance (HOMA-IR) index. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The results showed that the following indices were statistically significantly higher in the SH group: BMI (p < 0.05), diastolic blood pressure (p < 0.001), TC (p < 0.05), TG (p < 0.05) and basal insulin level (p < 0.05). Although MetS parameters were present in a higher per cent in the SH group, there was a significantly higher number of patients with hypertension and decreased HDL cholesterol (p < 0.05). More frequently, MetS was diagnosed in SH patients (46.67%) than in the control group (33.33%), although the difference was not statistically significant. These results indicated that the traditional cardiovascular risk factors were more frequently present in SH patients as compared to euthyroid participants. Our results did not confirm significantly higher presence of MetS in SH patients in comparison with euthyroid respondents.

Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.

Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment-Insulin Resistance index was used to quantify insulin resistance. RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 ± 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model Assessment-Insulin Resistance index (1.30 ± 0.42 vs. 4.18 ± 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

Abstract 9379: Higher Levels of Plasminogen-Activator Inhibitor 1 Are Associated with Progression of Coronary Artery Calcification in Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study

Introduction: Relationships of inflammatory and hemostatic biomarkers with progression of coronary artery calcification (CAC) in asymptomatic women are unknown. Hypothesis: We assessed the hypothesis that C-reactive protein (CRP), fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), and tissue plasminogen activator antigen (tPA-ag) were associated with CAC progression in women free of known coronary heart disease (CHD) and stroke. Methods: CRP, fibrinogen, PAI-1, and tPA-ag were measured in SWAN Heart participants from the Pittsburgh and Chicago sites at baseline. CAC was obtained by CT scans and quantified by the Agatston score at baseline and after 2.3±0.5 years of follow-up. Significant CAC progression was defined as present if 1) CAC score was &gt;0 at follow-up in subjects with CAC score = 0 at baseline, 2) annualized change in CAC score was ≥10 in subjects with 0&lt;CAC score&lt;100 at baseline, and 3) annualized percent change in CAC score was ≥10% in subjects with CAC score ≥100 at baseline. Univariable and multivariable logistic regression were used for statistical analyses. The novel biomarkers were log-transformed. Baseline CAC was transformed as log(CAC+1). Results: The study included 252 women (32.5% black, 67.5% white; 56.4% pre- and early perimenopausal, 30.6% late peri- and postmenopausal, and 13.1% hormone therapy users) with a mean age of 51.2±2.6 years at baseline. In unadjusted analyses, log(PAI-1) and log(tPA-ag) were positively and significantly associated with CAC progression (p&lt;0.05), but log(CRP) and log(fibrinogen) were not. Adjusted analyses included the following covariates: baseline CAC, age, site, race, menopausal status, income, education, systolic blood pressure, body mass index, Homeostasis Model Assessment insulin resistance index, family history of cardiovascular (CV) disease, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, CV medication use, and current smoking. Only log(PAI-1) was significantly associated with CAC progression (OR: 1.91; 95% CI: 1.24-2.93; p=0.003). Conclusions: In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CHD risk factors.

Abstract 9509: Heart Fat, but Not Peri-Aortic Fat Depots Were Significantly Associated With Presence and Severity of Coronary Calcification in Women at Midlife: The Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study

Introduction: Increasing evidence demonstrates a role of cardiovascular fat in the pathogenesis of CAD. It is unknown whether heart and vascular fat depots are related to atherosclerotic burden in women transitioning through menopause, a time of increasing CAD risk. Hypothesis: We hypothesize that volumes of epicardial (EAT), pericardial (PAT), total heart (TAT=EAT+PAT) and peri-aortic (PVAT) adipose tissues are associated with presence and severity of coronary artery calcification (CAC) in a sample of white and black midlife women. Methods: CAC and cardiovascular fat depots were quantified by electron beam CT. Outcomes were presence of CAC (none vs. any: Agatston score &gt;0), and severity of CAC (CAC Agatston score). Logistic and tobit regression were used. Final models were adjusted for age, race, study site, menopausal status, obesity (BMI ≥30 Kg/m 2 ), systolic blood pressure, lipids, homeostasis model assessment insulin resistance index, current smoking, physical activity, comorbidity (history of hypertension, stroke, angina, heart attack or diabetes) and medication use (cholesterol lowering, antihypertensive or antidiabetic medications). Results: The study included 509 women (37.9% black; 58.4% pre-/early perimenopausal, 41.6% late peri-/postmenopausal) aged 46-59 years with data on any of the 4 fat depots. CAC was found in 47.4% of the participants. Odds ratios (95% CI) from final logistic regression models showed that higher volumes of EAT (2.43 (1.22, 4.86), PAT (1.57 (1.04, 2.37), and TAT (2.43 (1.22, 4.87), were significantly associated with higher odds of presence of CAC. Similarly, tobit regression models showed that higher volumes per 1 log-unit increase of EAT (β (SE): 28.0 (10.7)), PAT (16.5 (6.6)), and TAT (30.0 (10.7)), were significantly associated with greater severity of CAC in final adjusted models. PVAT was not associated with either CAC presence or severity in final models. Conclusions: Heart fat (EAT, PAT and TAT), but not peri-aortic fat were independently associated with greater presence and severity of CAC in women at midlife, suggesting that local cardiovascular fat depots may contribute to CAD in midlife women. Future work is warranted to understand the underlying mechanistic pathways.

Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices

Objective: To develop a predictive index based on high sensitivity C-reactive protein (hs-CRP), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) measurements for early diagnosis of gestational diabetes mellitus (GDM).Methods: Healthy pregnant women who were screened for GDM during their first antenatal visit were included in this retrospective cohort study. FPG, FPI and serum hs-CRP concentrations were measured between weeks 11 and 14. A two-step glucose challenge test was carried out between gestational weeks 24 and 28. Fasting glucose/insulin ratio (FIGR), Homeostatic Model Assessment Insulin Resistance (HOMA-IR), HOMA-β indices and Quantitative Insulin Sensitivity Check Index (QUICKI) were used to estimate insulin sensitivity and β-cell function.Results: Of the 450 women who were eligible for the study, 49 (11.2%) were diagnosed with GDM at weeks 24–28. The median FPG and hs-CRP levels were higher in the GDM diagnosed women compared to the others. Comparison of accuracy measures resulted in the highest specificity (87.2%; 95% CI 83.5–90.1) and diagnostic odds ratio (3.9; 95% CI 2.1–7.6) for hs-CRP.Conclusion: FPG and hs-CRP in the first trimester are correlated with later development of GDM in the pregnancy. In our study, FPG provided a better sensitivity while hs-CRP exhibited a better specificity for prediction of GDM.

Epigallocatechin gallate prevents inflammation by reducing macrophage infiltration and inhibiting tumor necrosis factor-α signaling in the pancreas of rats on a high-fat diet

In this study, we hypothesized that epigallocatechin gallate (EGCG) would suppress inflammation in the pancreas, and thus, we investigated the effects that EGCG administration had in the pancreas of rats fed a high-fat diet (HFD). To test our hypothesis, 30 male Sprague-Dawley rats were divided into 2 groups: normal diet (control) group and HFD group. When there was a significant difference in body weight between the 2 groups (P < .05), the HFD group was further divided into 2 subgroups: the HFD group (HFD, n = 10, 16 weeks) and the EGCG group (HFD + 3.2 g/kg EGCG, n = 10, 16 weeks). Metabolite levels and the expression of inflammatory markers (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], and toll-like receptor 4) were measured using standard biochemical techniques. Insulin secretion and pancreatic histology were also evaluated. Epigallocatechin gallate significantly decreased fasting insulin levels as well as the homeostasis model assessment–insulin resistance index. In the HFD group, the average glucose infusion rate and the TNF-α and IL-6 levels increased, whereas toll-like receptor 4 and TNF receptor-associated factor-6 did not. A pathologic analysis of pancreatic tissue revealed an increase in inflammatory TNF-α and infiltrating CD68+ macrophages in the islets of the HFD rats, but rarely is this observed in the in the HFD + EGCG rats. Overall, these data suggest that EGCG suppresses inflammation, partially reverses metabolic abnormalities, and ultimately increases insulin sensitivity in the pancreas of HFD rats.

Bone mineral density in women with polycystic ovary syndrome.

PurposePCOS is a complex disorder and various features of this disorder may have great importance for bone metabolism. The aim of the study was to determine the relationship between existing hormonal disorders, and bone mineral density (BMD) in young women with PCOS.Methods69 reproductive-aged PCOS women and 30 age-matched healthy controls were enrolled to the study women. In each individual we assessed the body mass index (BMI). We evaluated the serum concentrations of: gonadotropins, prolactin (PRL), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), testosterone (T), thyroid stimulating hormone (TSH), free thyroxine (fT4). We used the Homeostatic Model Assessment–Insulin Resistance Index (HOMA–IR) to diagnose insulin resistance. Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA).ResultsThe PCOS women had lower BMD values as compared to the controls (1.057 ± 0.1260 vs. 1.210 ± 0.1805 g/cm2, p < 0.0002). In the analysis of PCOS patients according to BMI, only in the subgroup of the normal weight PCOS we find significantly lower BMD in comparison to controls (p = 0.0049). In patients with PCOS, BMD was positively correlated with insulin concentration and HOMA–IR. In the controls Z-score values were positively correlated with insulin concentration and HOMA–IR.ConclusionsThe deleterious effect of estrogen deficiency on bones in PCOS is not balanced by androgen overproduction. Women with PCOS had significantly lower BMD of the lumbar spine compared to controls. Insulin seems to be one of the most important positive bone growth stimulators.