Jigar Bhagatwala

Dietary Sodium, Adiposity, and Inflammation in Healthy Adolescents

OBJECTIVES: To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. METHODS: A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. RESULTS: The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05). CONCLUSIONS: The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption.

Adolescent Fiber Consumption Is Associated with Visceral Fat and Inflammatory Markers

CONTEXT The link between adolescent fiber consumption, inflammation, and body fat distribution has not been investigated. OBJECTIVE This study investigated associations of dietary fiber intake with inflammatory-related biomarkers and robust measures of total and central adiposity in a sample of 559 adolescents aged 14-18 yr (49% female, 45% Black). METHODS Fasting blood samples were measured for leptin, adiponectin, resistin, C-reactive protein, and fibrinogen. Diet was assessed with four to seven 24-h recalls, and physical activity was determined by accelerometry. Fat-free soft tissue mass and fat mass were measured by dual-energy x-ray absorptiometry. Visceral adipose tissue was assessed using magnetic resonance imaging. RESULTS Multiple linear regression, adjusting for age, race, Tanner stage, fat-free soft tissue mass, energy intake, and physical activity, revealed that dietary fiber intake was inversely associated with fat mass and serum leptin in males (all P < 0.03) but not in females. In both genders, dietary fiber intake was negatively associated with visceral adipose tissue, plasma C-reactive protein, and plasma fibrinogen and positively associated with plasma adiponectin (all P < 0.05). No relations were found between dietary fiber intake and plasma resistin in either males or females. CONCLUSION Our adolescent data suggest that greater consumption of dietary fiber is associated with lower visceral adiposity and multiple biomarkers implicated in inflammation.

Circulating 25-Hydroxyvitamin D Concentrations Are Correlated With Cardiometabolic Risk Among American Black and White Adolescents Living in a Year-Round Sunny Climate

OBJECTIVE Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population. RESEARCH DESIGN AND METHODS 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP). RESULTS Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = −0.32, P < 0.01), fibrinogen (r = −0.05, P = 0.03), glucose (r = −0.16, P = 0.02), HOMA-IR (r = −0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = −0.10, P = 0.02), and diastolic BP (r = −0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates. CONCLUSIONS Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.

Arterial Stiffness and Pulse-Pressure Amplification in Overweight/Obese African- American Adolescents: Relation With Higher Systolic and Pulse Pressure

BACKGROUND Obesity is associated with a higher systolic blood pressure (BP) and pulse pressure (PP) in African-American youths, increasing their risk for developing hypertension. However, it is unknown whether arterial stiffness and wave reflection are associated with a higher systolic BP and PP or with smaller PP amplification in overweight/obese (OW/OB) African-American adolescents. METHODS We measured carotid-femoral pulse wave velocity (CF-PWV), carotid-radial PWV (CR-PWV), the augmentation index (AIx) adjusted to a heart rate of 75 bpm (AI75), the augmentation pressure (AugP), PP amplification, and body composition in 227 healthy African-American adolescents (age, 16.9 ± 0.2 years; 54% male). RESULTS Adolescents who were OW/OB (n = 86, body mass index (BMI) ≥ 85th percentile) demonstrated 5%-6%, 13%-16%, and 2.5% higher aortic and brachial systolic BP, brachial and aortic PP, and mean arterial pressure (MAP), respectively (all P < 0.05), than adolescents of normal-weight (NW, n = 141, BMI < 85th percentile). The OW/OB adolescents had a 7% higher CF-PWV, 5% lower CR-PWV, and 3.5% lower PP amplification than the NW group (all P < 0.05), but no differences in AI75 or AugP. In the entire cohort after adjustment for age, sex, heart rate, height, and MAP, CF-PWV was positively correlated, and CR-PWV and PP amplification were negatively correlated, with total and abdominal/hip adiposity. Additionally, CF-PWV, AI75, and AugP were positively correlated with MAP and negatively correlated with PP amplification. CR-PWV, AI75, and AugP were negatively correlated with brachial and aortic PP. CONCLUSIONS Higher aortic stiffness is associated with smaller PP amplification with increasing adiposity in African-American adolescents. Whether a reduction in PP amplification predicts increased CVD risk in obese African-American adolescents requires further study.

Cytokine profiling of young overweight and obese female African American adults with prediabetes.

Approximately 5-10% of subjects with prediabetes become diabetic every year. Inflammation is involved in the development of obesity-related type 2 diabetes (T2D). However, to date, the relationship between inflammation and prediabetes, defined by hemoglobin A1c (HbA1c) ≥5.7 and <6.5%, remains largely unexplored, especially in African Americans. Therefore, in this study we examined a comprehensive panel of 13 cytokines involved in the inflammatory response in overweight/obese subjects with prediabetes. A total of 21 otherwise healthy, overweight/obese, young adult African American females with prediabetes, together with 20 matched overweight/obese controls, were selected for this study. Plasma cytokines were assessed by multiplex cytokine profiling. Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p<0.05). Plasma concentrations of all the other cytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the prediabetic group, but failed to reach statistical significances. Upon merging both groups, HbA1c was found to be positively correlated with IFN-γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. This study demonstrates elevated levels of various pro-inflammatory cytokines in overweight/obese young subjects with prediabetes, which place them at higher risk of developing T2D and cardiovascular diseases. Our data also call for further investigations in animal models and population cohorts to establish the roles of a variety of pro-inflammatory cytokines in the early development of obesity-related T2D.

Plasma kallistatin is associated with adiposity and cardiometabolic risk in apparently healthy African American adolescents.

OBJECTIVE It is generally recognized that obesity and cardiometabolic risk are more prevalent in African Americans. Kallistatin, a novel tissue kallikrein inhibitor, has anti-inflammatory and anti-oxidant properties. Thus, the goal of this study was to examine the relationships among plasma kallistatin levels, adiposity and cardiometabolic risk factors in African American adolescents. MATERIALS/METHODS Plasma kallistatin levels were determined in 318 apparently healthy African American adolescents (aged 14-19 years, 48.1% females) by enzyme-linked immunosorbent assay. RESULTS Plasma kallistatin levels did not differ between males (27.9±11.2 μg/mL) and females (26.8±11.0 μg/mL) (p=0.47). Plasma kallistatin levels were inversely correlated with percent body fat (% BF, r=-0.13, p=0.04), total cholesterol (r=-0.28, p<0.01), low density lipoprotein cholesterol (LDL, r=-0.30, p<0.01) and interleukin-6 (r=-0.14, p=0.05), but positively correlated with adiponectin (r=0.16, p=0.03) and high density lipoprotein (HDL, r=0.17, p=0.02). These correlations remained significant after adjustment for age, sex and body mass index percentiles. Stepwise multiple linear regression analysis showed that LDL cholesterol alone explained 14.2% of the variance in kallistatin, while % BF and adiponectin explained an additional 3.6% and 2.8% of the variance, respectively. CONCLUSIONS The present study demonstrates that plasma kallistatin levels are inversely associated with adiposity, adverse lipid profiles and inflammation in apparently healthy African American adolescents. As a potent antioxidant and anti-inflammation agent, kallistatin may also hold therapeutic promise in cardiometabolic disorders.

Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings.

Objectives Understanding of the influence of vitamin D deficiency on epigenome will provide novel insights into the chronic disease risk. We tested our hypotheses that 1) vitamin D deficiency is associated with global hypomethylation and this association may be race/ethnicity dependent; and 2) vitamin D supplementation will increase global DNA methylation level. Methods A two-stage design, cross-sectional observation followed by a 16 week randomized, double- blinded, placebo-controlled trial (RCT) of vitamin D3 supplementation, was undertaken. Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlashTM Methylated DNA Quantification kit (Epigentek). Global methylation data was obtained from 454 Caucasians and African Americans (42%) in the observation cohort and 58 African Americans with vitamin D deficiency in the dose responsive RCT. Results In the cross-sectional study, African Americans had lower %5-mC than Caucasians (P = 0.04). A significant interaction was detected between plasma 25(OH)D and race on %5-mC (P = 0.05), as a positive association was observed between plasma 25(OH)D and %5-mC in African Americans (β = 0.20, p<0.01), but not in Caucasians (β = 0.03, p = 0.62). In the 16-week RCT, a dose-response benefit of vitamin D3 supplementation was observed for %5-mC, as indicated by a significant linear upward trend (-0.01 ± 0.01%, placebo; 0.11 ± 0.01%, ~600 IU/day; 0.30 ± 0.01%, ~2,000 IU/day; and 0.65 ± 0.01%, ~4,000 IU/day group; P-trend = 0.04). Conclusions Vitamin D deficiency is associated with global hypomethylation in African Americans. Vitamin D3 supplementation increases global DNA methylation in a dose-response manner in African Americans with vitamin D deficiency.

High sodium intake is associated with short leukocyte telomere length in overweight and obese adolescents

Background/objectives:Telomere shortening has an important role in cellular aging. However, the impact of high sodium intake, an important risk factor of age-related diseases, on telomere shortening remains unknown. Therefore, we examined the relationship between high dietary sodium intake and leukocyte telomere length (LTL), particularly in the context of obesity, as obesity increases salt sensitivity.Subjects/methods:LTL was determined by a quantitative polymerase chain reaction method in 766 adolescents aged 14–18 years (50% females, 49% African Americans). Dietary sodium intake was assessed by seven independent 24-h dietary recalls. We divided the sample into low sodium (mean 2388±522 mg per day) or high sodium groups (mean 4142±882 mg per day) based on the median value (3280.9 mg per day).Results:In the entire cohort, there was no significant association between sodium intake and LTL (r=−0.05, P=0.24). However, there was a significant interaction between sodium intake and obesity status (P=0.049). Further multiple linear regression analyses revealed that higher dietary sodium intake was associated with shorter LTL in the overweight/obese group (body mass index ⩾85th percentile, β=−0.37, P=0.04), but not in the normal-weight group (β=0.01, P=0.93) after adjusting for multiple confounding factors. In the overweight/obese group, LTL was significantly shorter in the high sodium intake subjects vs low sodium intake subjects (1.24±0.22 vs. 1.32±0.20, P=0.02), but not the normal-weight group (1.29±0.24 vs 1.30±0.24, P=0.69).Conclusions:Higher dietary sodium intake is associated with shorter telomere length in overweight and obese adolescents.

Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial

Background Clinical trials are scant and equivocal on whether vitamin D can ameliorate arterial stiffness, particularly in populations at high risk for vitamin D deficiency and cardiovascular disease (CVD). This study determined the dose-response effects of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency. Methods Seventy overweight African Americans (aged 13–45 years) with serum 25-hydroxyvitamin D [25(OH)D] levels ≤ 20 ng/mL were randomized to monthly oral supplementation of 18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), or 120,000 IU (~4000 IU/day, n = 18) of vitamin D3 or placebo (n = 17) for 16-weeks. The arterial stiffness measurements, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV, were assessed by applanation tonometry at baseline and 16 weeks. Results Vitamin D3 supplementation demonstrated a dose-response increase in serum 25(OH)D concentrations between groups (P<0.01). A significant downward linear trend was observed for carotid-femoral PWV (P<0.01), as the mean changes in carotid-femoral PWV across the four treatment groups were 0.13 m/s (95% CI: -0.24, 0.51 m/s) for placebo, 0.02 m/s (95% CI: -0.34, 0.38 m/s) for 600 IU/day group, -0.11 m/s (95% CI: -0.50, 0.27 m/s) for the 2,000 IU/day group, and -0.70 m/s (95% CI: -1.07, -0.32 m/s) for the 4,000 IU/day group. Findings were similar for carotid-radial PWV (P = 0.03), as the mean changes in carotid-radial PWV across the four treatment groups were 0.24 m/s (95% CI: -0.45, 0.92 m/s) for placebo, 0.09 m/s (95% CI: -0.54, 0.73 m/s) for 600 IU/day group, -0.57 m/s (95% CI: -1.20, 0.07 m/s) for the 2,000 IU/day group, and -0.61 m/s (95% CI: -1.25, 0.02 m/s) for the 4,000 IU/day group. Conclusion Arterial stiffness was improved by vitamin D3 supplementation in a dose-response manner in overweight African Americans with vitamin D deficiency.

Colonoscopy — Indications and Contraindications

This chapter discusses some of the major indications and contraindications for colonoscopy. Advances in colonoscopic techniques have expanded the role of colonoscopy beyond conventional screening, surveillance, and diagnosis to various complex therapeutic and interventional utilities. Several guidelines with new information are being published and updated regularly in the field of colonoscopy and are currently used in clinical practice. However, there is still a lack of welldesigned randomized clinical trials investigating the role of colonoscopy in early diagnosis and treatment of various conditions and its impact on long-term survival and disease status. Nevertheless, retrospective observational studies and a few randomized clinical trials abundantly supply data supporting the role of colonoscopy in the diagnosis and management of colonic pathologies in the absence of comparable alternatives.