Prevalence of 'hypertriglyceridemic waist' in men who participated in the Quebec Health Survey: association with atherogenic and diabetogenic metabolic risk factors

BACKGROUND: A triad of metabolic markers (high insulin and apolipoprotein B levels, and small, dense, low density lipoprotein particles) is associated with a substantially increased risk of coronary artery disease (CAD) in men. Also, the simultaneous presence of an elevated waist circumference (90 cm or greater) and moderate hypertriglyceridemia (triglyceride concentration 2.0 mmol/L or higher) in men has been shown to be associated with this atherogenic metabolic triad, with a probability of more than 80%. OBJECTIVES: To quantify the prevalence of the 'hypertriglyceridemic waist' phenotype in a sample of adult men and to compare the metabolic risk profile of nondiabetic men with hypertriglyceridemic waist with the CAD risk profile of patients with type 2 diabetes. METHODS: The sample of people who participated in the Quebec Health Survey was used to obtain representative data on the prevalence and distribution of cardiovascular disease risk factors in the Quebec population. Fasting plasma lipoprotein-lipid, insulin and glucose concentrations were measured, and anthropometric measurements were taken in a sample of 907 men. RESULTS: Among men who participated in the Quebec Health Survey, 19% had an elevated waist circumference (90 cm or greater) plus elevated triglyceride levels (2.0 mmol/L or higher). Men with this hypertriglyceridemic waist phenotype were characterized by the highest values for fasting plasma insulin, and the highest total cholesterol to high density lipoprotein cholesterol ratios. They also displayed a metabolic risk profile that was deteriorated to the same extent as that of men with diabetes who had participated in the survey. CONCLUSIONS: The results of the the present study of men who participated in the Quebec Health Survey provide further evidence that the simultaneous measurement and interpretation of waist circumference and fasting triglyceride concentrations may improve the physician's ability to identify abdominally obese men with atherogenic and diabetogenic profiles. Furthermore, this high risk clinical phenotype is highly prevalent (about 20%) among adult men.     

Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men

The present study examined the associations between a major adipokine, adiponectin, and adiposity indices as well as metabolic risk variables in a sample of 190 untreated asymptomatic men. Anthropometric measurements and a complete fasting plasma lipoprotein and lipid profile were obtained, and subjects underwent an oral glucose tolerance test. Fasting plasma adiponectin concentrations were determined by an ELISA. Although all adiposity and adipose tissue (AT) distribution indices were negatively correlated with plasma adiponectin levels (-0.14 /=30 kg/m(2)) but who markedly differed in their level of visceral AT (< vs. >/=130 cm(2); n = 15) revealed significant differences in adiponectin levels (7.0 +/- 3.0 vs. 11.1 +/- 4.9 microg/ml; P < 0.02 for men with high vs. low visceral AT, respectively). Finally, when men were stratified into tertiles of visceral AT and further classified on the basis of the 50th percentile of adiponectin levels (8.8 microg/ml), a 3 x 2 ANOVA revealed an independent contribution of adiponectin on the variation of high-density lipoprotein cholesterol levels (P < 0.002) and of the glucose area (P < 0.02). These results support the notion that adiponectin concentration is influenced to a greater extent by visceral than sc obesity. Furthermore, adiponectin predicts glucose tolerance and plasma high-density lipoprotein cholesterol levels in a manner that is partly independent from the contribution of visceral adiposity.     

Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men

OBJECTIVE: This study examined the relationships of two inflammatory cytokines, IL-6 and TNF-alpha, to visceral adiposity and indices of plasma glucose-insulin homeostasis. RESEARCH DESIGN AND METHODS: Plasma levels of IL-6 and TNF-alpha were measured in 189 untreated asymptomatic men (aged 43.7 +/- 7.8 yr; body mass index 29.0 +/- 4.3 kg/m(2); waist girth 98.6 +/- 10.3 cm). RESULTS: Significant and positive associations were found between both cytokines with adiposity and adipose tissue distribution indices (0.15 < or = r < 0.32; P < 0.05) as well as plasma glucose-insulin homeostasis variables (0.22 < or = r < 0.28; P <0.05). Comparison of two subgroups, each composed of 32 overweight men (> or =25 kg/m(2)) with similar body mass index values (28.7 kg/m(2) in both groups) but with markedly different levels of visceral adipose tissue (< vs. > or = 130 cm(2)), revealed significant differences only for IL-6 levels (1.42 +/- 1.15 vs. 0.86 +/- 0.52 pg/ml; P < 0.02 for men with high vs. low visceral adipose tissue, respectively). Finally, when subjects were stratified on the basis of their respective concentrations of IL-6 and TNF-alpha (using the 50th percentile of their overall distribution), an ANOVA revealed an independent contribution of IL-6 to the variation of fasting insulin (P < 0.01) and each of these two cytokines to the variation of insulin levels measured after a 75-g oral glucose challenge (P <0.01 for IL-6 and P < 0.05 for TNF-alpha). CONCLUSIONS: Because IL-6 appeared to be clearly associated with visceral adiposity, TNF-alpha rather showed associations with indices of total body fatness. Thus, TNF-alpha may contribute to the insulin resistance of overall obesity, whereas IL-6 may be one of the mediators of the hyperinsulinemic state specifically related to excess visceral adiposity.     

Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.     

Influence of obesity indices, metabolic parameters and age on cardiac autonomic function in abdominally obese men

Heart rate variability (HRV) is affected by age, hyperglycemia and accumulation of body fat. This study compares the predictive value of four measurements of adiposity/obesity on HRV and investigates the specific role of age, metabolic contributors and degree/distribution of fat in HRV alterations. The sample consisted of 97 non-diabetic and non-medicated men with features of the metabolic syndrome (50 ± 8 years of age, body mass index [BMI] 31 ± 3 kg/m², waist circumference [WC] 107 ± 9 cm, triglycerides 2.3 ± 0.7 mmol/L, fasting glucose 6.0 ± 0.5 mmol/L, insulin 156 ± 71 pmol/L; mean ± SD). WC, BMI, percent body fat (% fat, from dual energy X-ray absorptiometry) and visceral adipose tissue volume (VAT, from computed tomography) were used as measures of adiposity/obesity. HRV measures were obtained from 24-h, day- and night-time segments of Holter recordings. BMI presented no independent association with HRV. Percentage fat was the strongest obesity index to be associated with HRV: 24-h pNN50, rMSSD, HF and daytime pNN50, rMSSD, HF and LF (?0.27 ≤ std β ≤ ?0.20, P < .05). VAT was associated with 24-h SDNN, LF (std β = ?0.25 and ?0.20, P < .05, respectively) and daytime SDNN (std β = ?0.24, P < .05) while WC was associated with nighttime SDNN and SDANN (std β = 0.22 and 0.32, P < .05). In addition, age, fasting glucose, 2-h oral glucose tolerance test and triglycerides presented independent association with HRV. Adiposity/obesity measurements seem to be differently associated with HRV. An approach considering the combination of age, obesity and glucose metabolism factors could be helpful in the global cardiovascular risk management in abdominally obese men.     

Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer.

PURPOSE: This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. PATIENTS AND METHODS: A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2) plus paclitaxel 200 mg/m(2) as a 3-hour infusion (AP) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (AC) every 3 weeks for 4 courses followed by surgery. RESULTS: A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). CONCLUSION: The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.     

Update on docetaxel and breast cancer

Docetaxel (Taxotère) has been developed in breast cancer during the last decade. First its activity in monotherapy was proven in metastatic setting after failure of anthracycline therapy. Then the association with anthracycline demonstrated substantial activity leading to its development in early stages of breast cancer and its incorporation in adjuvant and neoadjuvant settings. Recently the first adjuvant trial comparing the association TAC versus FAC was presented. In the TAC arm, the disease free survival was better comparing with FAC (p = 0.0011) and survival was better in the subgroup with less than four positive lymph nodes. In the neoadjuvant setting, the incorporation of docetaxel after an anthracycline-based regimen (protocols Aberdeen and NSABP-B27) led to better clinical response, subsequently to better breast conservation and more important the increase of the pathological response rate. Improvement of survival has been reported in the Aderbeen study but a longer follow-up of the NSABP B27 study is required to confirm the impact of Taxotère in the outcome of breast cancer. The next step will be the development of the combination of the most active chemotherapeutic regimen with targeted therapies according to molecular characteristics of the tumor. The integration of trastuzumab with taxane-based chemotherapy has already demonstrated high activity in metastatic breast cancer with overexpression of HER2 and adjuvant trials are ongoing.     

3.1 Scholarship and the university

Universities now exist in an environment of increasing accountability for their academic performance, both in teaching and research. Dental schools are expected to meet the academic expectations of their parent university and, in addition, to contribute to the health-care needs of the community. Individual staff members must achieve collectively the performance targets required of their school and individually must develop skills and expertise in their academic and clinical activities to merit tenure and promotion. This discussion examines the issues which impact on current problems of recruitment and retention of academic staff in dental schools internationally. The essential issue is career development in a manner which maintains the values that will ensure the credibility of dentistry as a scientifically based discipline and profession, while balancing the achievable academic needs with the added demands of achieving specialist clinical skills. Central to this balance is recognition that scholarship, which provides the bridge between research and teaching, can be broadly defined and that different individuals can be scholarly in a range of ways. Increasingly, schools are recognizing the importance of providing structured opportunities and guidance for career development of younger staff and of the need for flexibility in their criteria for tenure and promotion, recognizing that a diversity of individual strengths and teamworking are necessary both for the collective performance of the institution and the morale and development of the individual.     

Secondary ion mass spectrometry as a tool for investigating radiopharmaceutical distribution at the cellular level: the example of I-BZA and (14)C-I-BZA.

Further development of nuclear medicine for imaging and internal radiotherapy demands a precise knowledge of the tissue and cellular distribution of radiopharmaceuticals. Ion microscopy (secondary ion mass spectrometry [SIMS]) may be particularly useful in this respect. We used SIMS to study the biodistribution of the melanoma-targeting molecule N-(2-diethylaminoethyl)-4-iodobenzamide (I-BZA), both in its native state and radiolabeled with (14)C. METHODS: C57BL6/J1/co mice bearing pulmonary colonies of B16 melanoma cells were injected with I-BZA or (14)C-I-BZA. Appropriate tissues were fixed and included in epoxy embedding resin for SIMS studies. The distribution of unlabeled I-BZA was studied by detecting its stable iodine atom ((127)I). (14)C-I-BZA distribution was studied by dual detection of (127)I and (14)C. The time course of I-BZA concentrations at sites of tissue fixation was studied by measuring the signal ratio of (14)C and the naturally occurring isotope (13)C. RESULTS: SIMS showed that I-BZA concentrated in the cytoplasm of tumoral melanocytes (melanoma cells) and in the cytoplasm of tumor-infiltrating macrophages (melanophages). I-BZA was also detected in the cytoplasm of normal melanocytes in the pigmented structures of skin and eye. Interpretation of I-BZA distribution by using electron micrographs of adjacent sections showed that the intracytoplasmic melanin-rich organelles (melanosomes) were responsible for I-BZA retention. The distributions of (127)I and (14)C after (14)C-I-BZA injection were identical, even when I-BZA was separately labeled with (14)C at 2 different positions, indicating the stability of the amide bond of I-BZA. The time course of the (14)C/(13)C ratio in the melanosomes of melanoma cells suggested a retention half-life of about 38 h. CONCLUSION: Contrary to previous suggestions that I-BZA fixes principally to sigma-1 membrane receptors, our results strongly indicate that I-BZA associates with intracytoplasmic melanin pigments. Early I-BZA accumulation, in both melanocytes and melanophages, suggests that this compound fixes to preformed melanin rather than being incorporated during de novo melanin synthesis. These quantitative and qualitative data obtained with I-BZA illustrate the excellent potential of SIMS for studying the biologic fate of radiopharmaceuticals.