Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent Girls.

OBJECTIVE: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17-20 years). METHODS: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10 years, in the National Heart, Lung, and Blood Institute's National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9-17 years: <1 egg/wk (n = 361), 1 to <3 eggs/wk (n = 703), and ≥3 eggs/wk (n = 328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors. RESULTS: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p = 0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance. CONCLUSION: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance.

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds.

OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity. METHODS: PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]). RESULTS: In 2006, ≤25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile <20%; ALT/AST ≤25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P<.0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P<.0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P<.05). CONCLUSION: Despite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011.

Eggs and a Fiber-Rich Diet Are Beneficially Associated with Lipid Levels in Framingham Offspring Study Adults.

Background: For many years, United States' dietary policy recommended limiting egg intake to no more than 3/wk in the belief that restricting dietary cholesterol would lower plasma cholesterol levels and thereby reduce the risk of cardiovascular disease. The evidence supporting these recommendations is controversial. Objectives: To examine the impact of eggs, a major contributor to dietary cholesterol intake, on lipid levels and to determine whether these egg effects are modified by other healthy dietary factors in adults. Methods: Males and females aged 30-64 y with available 3-d diet record data, without cardiovascular disease and not taking lipid- or glucose-lowering medications in the prospective Framingham Offspring cohort were included (n = 1852). Analysis of covariance models were used to compare mean follow-up lipid levels adjusting for age, sex, BMI, and dietary factors. Cox proportional hazard's models were used to estimate risk for elevated lipid levels. Results: Consuming ≥5 eggs/wk was not adversely associated with lipid outcomes. Among men, consuming ≥5 (compared with <0.5) eggs/wk was associated with an 8.6 mg/dL lower total cholesterol level and a 5.9 mg/dL lower LDL cholesterol level, as well as lower triglycerides. Overall, higher egg intake combined with higher dietary fiber (compared with lower intakes of both) was associated with the lowest total cholesterol, LDL cholesterol, and LDL cholesterol-to-HDL cholesterol ratio. Finally, diets with higher (compared with lower) egg intakes in combination with higher total fish or fiber intakes, respectively, were associated with lower risks of developing elevated (>160 mg/dL) LDL cholesterol levels (hazard ratio: 0.61; 95% confidence interval: 0.44, 0.84; and HR: 0.70; 95% confidence interval: 0.49, 0.98, respectively). Conclusions: Higher egg intakes were beneficially associated with serum lipids among healthy adults, particularly those who consumed more fish and dietary fiber.

Arteriolar function in visceral adipose tissue is impaired in human obesity.

OBJECTIVE: The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS: In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 µm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS: Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.

Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults.

The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30-64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazard's models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (p = 0.0004) and SBP (p = 0.0284) after four years of follow-up. Higher egg intakes led to lower risks of developing IFG or T2D (HR: 0.72; 95% CI: 0.51-1.03) and high blood pressure (HBP) (HR: 0.68; 0.50-0.93). The beneficial effects of egg consumption were stronger in combination with other healthy dietary patterns. This study found that regular egg consumption as part of a healthy diet had long-term beneficial effects on blood pressure and glucose metabolism and lowered the long-term risks of high blood pressure and diabetes.

Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans.

Inflammation and infiltration of immune cells in white adipose tissue have been implicated in the development of obesity-associated insulin resistance. Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects. In this study, we examined the relationships between AMPK activity, the expression of multiple inflammatory markers in visceral (mesenteric and omental) and abdominal subcutaneous adipose tissue, and whole-body insulin sensitivity in morbidly obese patients (BMI 48±1.9 kg/m(2)) undergoing gastric bypass surgery. AMPK activity was assessed by Western-blots (P-AMPK/T-AMPK) and mRNA levels of various markers of inflammation by qRT-PCR. Patients were stratified as insulin sensitive obese or insulin-resistant obese according to their HOMA-IR values. The results indicate that AMPK activity is lower in visceral than in subcutaneous abdominal adipose tissue of these patients and that this is associated with an increased expression of multiple inflammatory genes. They also revealed that AMPK activity is lower in adipose tissue of obese patients who are insulin resistant (HOMA-IR>2.3) than in BMI-matched insulin sensitive subjects. Furthermore, this difference was evident in all three fat depots. In conclusion, the data suggest that there are close links between reduced AMPK activity and inflammation in white adipose tissue, and whole-body insulin resistance in obese humans. Whether adipose tissue AMPK dysregulation is a causal factor for the development of the inflammation and insulin resistance remains to be determined.

Maladaptive enlargement of the brachial artery in severe obesity is reversed with weight loss.

Maladaptive peripheral arterial remodeling, which leads to large arteries with low shear stress, may be associated with increased cardiovascular risk. We tested the hypothesis that arterial enlargement in severe obesity represents maladaptive remodeling and that weight reduction would reverse this process. We evaluated brachial arterial diameter and flow using ultrasound in 244 severely obese patients (age 44 +/- 11 years, 80% female, body mass index (BMI) 46 +/- 9 kg/m) at baseline and in a group of 67 subjects who experienced weight loss at 1 year. Higher BMI was associated with larger brachial artery diameter (p = 0.01) and lower shear stress (p = 0.008), indicating maladaptive remodeling. Significant (> or = 10%) weight reduction was associated with a decrease in resting arterial diameter (-0.19 +/- 0.47 mm, p = 0.02) along with a trend toward increased shear stress. Decreased systemic inflammation was associated with weight loss-induced reverse remodeling of the brachial artery. Our findings demonstrate the presence of maladaptive arterial remodeling in advanced obesity that was ameliorated by significant weight loss.

Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects.

OBJECTIVE: Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals. METHODS AND RESULTS: We collected subcutaneous abdominal fat in 77 obese subjects (BMI >or=30 kg/m(2)) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5+/-4.5 versus 2.6+/-1.9, P=0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5+/-4.4% versus 10.8+/-3.8%, P<0.05), as compared to subjects with quiescent noninflamed adipose architecture (n=27). Macrophage retention in fat was linked to upregulated tissue CD68 and tumor necrosis factor (TNF)-alpha mRNA expression in addition to increased plasma hs-CRP. CONCLUSIONS: In a cohort of obese subjects, we demonstrate that proinflammatory changes in adipose tissue are associated with systemic arterial dysfunction and insulin resistance. These findings suggest that adipose inflammation may be linked to vascular injury and increased cardiovascular risk in obese subjects.

Dietary Cholesterol Intake Is Not Associated with Risk of Type 2 Diabetes in the Framingham Offspring Study.

Identification of diet and lifestyle risk factors for prevention of type 2 diabetes mellitus (T2DM) is of great importance. The specific role of dietary cholesterol (DC) in T2DM risk is unclear. This study uses data from 2192 Framingham Offspring Study subjects to estimate the effects of DC alone and in combination with markers of a healthy diet and other lifestyle factors on fasting glucose and risk of T2DM or impaired fasting glucose (IFG) over 20 years of follow-up. Dietary data were derived from two sets of three-day food records. Statistical methods included mixed linear regression and Cox proportional hazard's modeling to adjust for confounding. There were no statistically significant differences in glucose levels over 20 years of follow-up across DC intake categories (.

Dietary Cholesterol, Lipid Levels, and Cardiovascular Risk among Adults with Diabetes or Impaired Fasting Glucose in the Framingham Offspring Study.

Previous recommendations to limit dietary cholesterol intake have been eliminated for most adults. Questions remain about whether dietary cholesterol has adverse cardiovascular effects among individuals with impaired fasting glucose or diabetes (IFG/T2DM). We used data for 993 adults (40.9% female), ages 35⁻<65 years, with prevalent IFG/T2DM in the prospective Framingham Offspring Study to address this question. Dietary cholesterol was assessed using 3-day diet records at exams 3 and 5 and used to classify subjects into sex-specific tertiles of mean cholesterol intake. Outcomes included fasting lipid levels over 20 years and incident cardiovascular disease (CVD). Statistical analyses included repeated measures mixed regression models and Cox proportional hazards models to adjust for confounding. Among adults with T2DM/IFG, there was no consistent association between dietary cholesterol intake and fasting low-density lipoprotein (LDL), high-density lipoprotein (HDL), LDL/HDL ratio, or triglycerides over 20 years of follow-up. In longitudinal analyses, the adjusted hazard ratio for CVD in the highest (vs. lowest) sex-specific tertile of cholesterol intake was 0.61 (95% CI: 0.41, 0.90). These analyses provide no evidence of an adverse association between dietary cholesterol and serum lipid levels or atherosclerotic CVD risk among adults with prevalent IFG/T2DM.

B lymphocytes in human subcutaneous adipose crown-like structures.

Accumulation of macrophages and T cells within crown-like structures (CLS) in subcutaneous adipose tissue predicts disease severity in obesity-related insulin resistance (OIR). Although rodent data suggest the B cell is an important feature of these lesions, B cells have not been described within the human CLS. In order to identify B cells in the human subcutaneous CLS (sCLS) in obese subjects and determine whether the presence of B cells predict insulin resistance, we examined archived samples of subcutaneous and omental fat from 32 obese men and women and related findings to clinical parameters. Using immunohistochemistry, we identified B (CD19(+)) and T cells (CD3 (+)) within the sCLS and perivascular space. The presence and density of B cells (B cells per high-power field (pHPF), T cells pHPF, and B cell:T cell (B:T) ratio) were compared with measures of insulin resistance (homeostasis model assessment (HOMA)) and other variables. In 16 of 32 subjects (50%) CD19(+) B cells were localized within sCLS and were relatively more numerous than T cells. HOMA was not different between subjects with CD19(+) vs. CD19(-) sCLS (5.5 vs. 5.3, P = 0.88). After controlling for diabetes and glycemia (hemoglobin A(1c) (HbA(1c))), the B:T ratio correlated with current metformin treatment (r = 0.89, P = 0.001). These results indicate that in human OIR, B cells are an integral component of organized inflammation in subcutaneous fat, and defining their role will lead to a better understanding of OIR pathogenesis and potentially impact treatment.

Reduced adipose tissue inflammation represents an intermediate cardiometabolic phenotype in obesity.

OBJECTIVES: The purpose of this study was to determine whether obese individuals with reduced adipose tissue inflammation exhibit a more favorable cardiovascular risk profile. BACKGROUND: Obesity is associated with a low-grade state of chronic inflammation that might be causally related to cardiometabolic disease. METHODS: With immunohistochemistry, we categorized obese individuals dichotomously as having inflamed fat (n = 78) or noninflamed fat (n = 31) on the basis of the presence (+) or absence (-) of macrophage crown-like structures (CLS) in subcutaneous abdominal fat biopsy samples. We compared their metabolic, vascular, and adipose tissue characteristics with lean subjects (n = 17). RESULTS: Inflamed CLS+ obese individuals displayed higher plasma insulin, homeostasis model assessment, triglycerides, glucose, blood pressure, high-sensitivity C-reactive protein, low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, and brachial artery flow-mediated dilation compared with lean subjects (p < 0.05). Adipose messenger ribonucleic acid expression of inflammatory genes including CD68, leptin, matrix metalloproteinase-9, CD163, and CD8A were significantly greater and vascular endothelial growth factor was lower in the CLS+ group (p < 0.05). In contrast, obese subjects with noninflamed fat exhibited a mixed clinical phenotype with lower insulin resistance, reduced proatherogenic gene expression, and preserved vascular function as in lean subjects. In multiple linear regression adjusting for age and sex, CLS status (beta = -0.28, p = 0.008) and waist circumference (beta = -0.25, p = 0.03) were independent predictors of flow-mediated dilation. CONCLUSIONS: These findings lend support to the novel concept that factors in addition to absolute weight burden, such as qualitative features of adipose tissue, might be important determinants of cardiovascular disease. Therapeutic modulation of the adipose phenotype might represent a target for treatment in obesity.

Long-term successful weight loss improves vascular endothelial function in severely obese individuals.

Obesity is associated with increased cardiovascular risk. Although short-term weight loss improves vascular endothelial function, longer term outcomes have not been widely investigated. We examined brachial artery endothelium-dependent vasodilation and metabolic parameters in 29 severely obese subjects who lost > or =10% body weight (age 45 +/- 13 years; BMI 48 +/- 9 kg/m(2)) at baseline and after 12 months of dietary and/or surgical intervention. We compared these parameters to 14 obese individuals (age 49 +/- 11 years; BMI 39 +/- 7 kg/m(2)) who failed to lose weight. For the entire group, mean brachial artery flow-mediated dilation (FMD) was impaired at 6.7 +/- 4.1%. Following sustained weight loss, FMD increased significantly from 6.8 +/- 4.2 to 10.0 +/- 4.7%, but remained blunted in patients without weight decline from 6.5 +/- 4.0 to 5.7 +/- 4.1%, P = 0.013 by ANOVA. Endothelium-independent, nitroglycerin-mediated dilation (NMD) was unaltered. BMI fell by 13 +/- 7 kg/m(2) following successful weight intervention and was associated with reduced total and low-density lipoprotein cholesterol, glucose, hemoglobin A(1c), and high-sensitivity C-reactive protein (CRP). Vascular improvement correlated most strongly with glucose levels (r = -0.51, P = 0.002) and was independent of weight change. In this cohort of severely obese subjects, sustained weight loss at 1 year improved vascular function and metabolic parameters. The findings suggest that reversal of endothelial dysfunction and restoration of arterial homeostasis could potentially reduce cardiovascular risk. The results also demonstrate that metabolic changes in association with weight loss are stronger determinants of vascular phenotype than degree of weight reduction.