Serum retinol levels are positively correlated with hemoglobin concentrations, independent of iron homeostasis: a population-based study.

Micronutrient interactions give rise to complex issues that have an impact on preventive strategies when multiple micronutrient deficiencies coexist. The aim of this population-based study was to determine the prevalence of vitamins A and E and iron deficiencies among women 15 to 49 years of age in the northern Persian Gulf region. We hypothesized that serum retinol levels may show correlations with hemoglobin (Hb) concentrations, independent of iron status. A total of 1242 nonpregnant women of reproductive age were selected via a multistage stratified random cluster sampling technique. Serum ferritin and soluble transferrin receptor levels were measured using enzyme immunoassay techniques. Serum retinol (vitamin A) and α-tocopherol (vitamin E) were determined for 727 women by high-performance liquid chromatography. The prevalence of anemia (Hb <12 g/dL), iron deficiency (serum ferritin <15 µg/L), and iron deficiency anemia was 8.7%, 25.4%, and 4.6%, respectively. Vitamin A (<0.7 µmol/L) and vitamin E (<11.6 µmol/L) deficiencies were found in 1.2% and 5.9% of the studied population, respectively. Multiple regression analysis revealed that serum retinol levels exhibit a significant association with Hb concentrations after controlling for serum ferritin levels, anemia associated with chronic disease, and risk factors for anemia. Therefore, most nonpregnant women of reproductive age in the northern Persian Gulf were found to have adequate serum vitamin A and E levels. However, the status of anemia and iron deficiency anemia could be considered a mild public health problem in this region. On the basis of multivariate analyses, we conclude that low serum retinol levels may contribute to anemia, independent of iron homeostasis.

Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women.

The bone and fat interface is implicated in the pathogenesis of postmenopausal osteoporosis. The association between circulating omentin-1 levels and bone mineral density (BMD) in postmenopausal women has never been assessed. A total of 382 healthy postmenopausal women were randomly selected. Omentin-1, visfatin, adiponectin, the receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin, high sensitivity C-reactive protein, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific enzyme-linked immunosorbent assay methods. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy X-ray absorptiometry. In multivariable-adjusted linear regression, serum omentin-1 levels were inversely correlated with BMD at the lumbar spine (ß=-0.11, p=0.020). In multiple regression analyses, serum visfatin and adiponectin levels were not significantly correlated with BMD at different skeletal sites after controlling for age, body mass index, and bone-related markers. However, the highest quartile of adiponectin compared to the lowest quartile, after adjusting for potential confounders, revealed an inverse association with BMD in the lumbar spine (ß=-0.19, p=0.010). In conclusion, circulating omentin-1 levels had an inverse correlation with BMD at the lumbar spine in Iranian postmenopausal women. To further understand the role of omentin-1 in bone and mineral metabolism, large-scale longitudinal studies focusing on BMD and osteoporotic fractures are warranted.

Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data.

BACKGROUND: Epidemiological studies on genital human papilloma viruses infection (HPVs) in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. RESULTS: Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic, or "high risk genotypes" and one genotype (HPV-66) was "probably carcinogenic." CONCLUSIONS: In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.

Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism.

Although it has been shown that osteocalcin functions as a hormone in the regulation of glucose metabolism and fat mass, no population-based study to date has addressed serum osteocalcin levels in relation to energy metabolism concurrent with bone metabolism in postmenopausal women. In a population-based study, cardiovascular risk factors, high-sensitivity C-reactive protein (hs-CRP), osteoprotegerin, receptor activator of nuclear factor-κB ligand, osteocalcin, CrossLaps, alkaline phosphatase, and bone mineral density (BMD) at the lumbar spine (L2-L4) and the proximal femur were measured in 382 Iranian postmenopausal women. In multiple logistic regression analysis, lower osteocalcin and CrossLaps levels were associated with a higher odds ratio (OR) of having type 2 diabetes mellitus when adjustments were made for age, hs-CRP, cardiovascular risk factors, BMD, and markers of bone metabolism [OR 5.17, CI (2.66-10.04), p < 0.0001 and OR 2.51, CI (1.37-4.61), p = 0.003, respectively]. However, lower alkaline phosphatase levels were associated with a lower OR of having type 2 diabetes mellitus [OR 0.28, CI (0.15-0.52), p < 0.0001] in regression analysis. No significant difference was found between serum osteocalcin levels of those with and without metabolic syndrome. Among the metabolic syndrome components, low osteocalcin levels had significant associations with elevated blood glucose [OR 1.89, CI (1.16-3.07), p = 0.010] and elevated waist circumference [OR 2.53, CI (1.13-5.67), p = 0.024] in multivariate analyses. In conclusion, serum osteocalcin was independently associated with glucose intolerance and abdominal obesity as the components of metabolic syndrome and type 2 diabetes mellitus in postmenopausal women. Since CrossLaps and alkaline phosphatase levels were independently associated with the presence of type 2 diabetes mellitus, the unique contribution of osteocalcin in glucose metabolism could not be concluded.

Correlation of circulating omentin-1 with bone mineral density in multiple sclerosis: the crosstalk between bone and adipose tissue.

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of osteoporosis and fractures. Adipose tissue-derived adipokines may play important roles in the osteoimmunology of MS. In order to determine whether omentin-1 and vaspin may be related to bone health in MS patients, we compared circulating levels of these recently identified adipokines, between MS patients and healthy controls. METHODS: A total of 35 ambulatory MS patients with relapsing-remitting courses were compared with 38 age- and sex-matched healthy controls. Bone mineral density (BMD) was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating omentin-1, vaspin, osteocalcin, osteopontin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, matrix metalloproteinase 9, C-reactive protein and 25-hydroxy vitamin D levels were evaluated by highly specific enzyme-linked immunosorbent assay methods. RESULTS: There was no significant difference between the two groups regarding bone-related cytokines, adipocytokines, and the BMD measurements of patients with MS and the healthy controls. However, in multiple regression analysis, serum omentin-1 levels were positively correlated with BMD at the femoral neck (ß = 0.49, p = 0.016), total hip (ß = 0.42, p = 0.035), osteopontin (ß = 0.42, p = 0.030) and osteocalcin (ß = 0.53, p = 0.004) in MS patients. No correlations were found between vaspin, biochemical, and BMD measures in both groups. CONCLUSIONS: Elevated omentin-1 serum levels are correlated with BMD at the femoral neck and the serum levels of osteocalcin and osteopontin in MS patients. Therefore, there is crosstalk between adipose tissue and bone in MS.

Influence of levothyroxine treatment on serum levels of soluble Fas (CD95) and Fas Ligand (CD95L) in chronic autoimmune hypothyroidism.

Fas/FasL-mediated apoptosis results in the destruction of thyrocytes in chronic autoimmune hypothyroidism (CAIH). In this study, we examined the serum levels of soluble Fas (sFas) and soluble sFas ligand (sFasL) in euthyroid patients with chronic autoimmune hypothyroidism, who were taking levothyroxine (euthyroid, LT4-CAIH), to investigate the possible role of thyroid hormone therapy in down-regulation of apoptotic factors. Fifty euthyroid patients with CAIH on levothyroxine (median of duration 36 months, range 6-228 months) were compared with 75 age- and sex-matched healthy individuals. Serum levels of soluble Fas and soluble Fas Ligand, autoantibodies to thyroid peroxide and thyroglobulin were measured using ELISA. Serum levels of sFas were significantly higher in the euthyroid, LT4-CAIH group [median 9.12 ng/ml, interquartile range (7.86-10.72 ng/ml)] than in the controls [6.11 ng/ml (5.60-6.81 ng/ml)] (P < 0.0001). Compared with controls [80.33 pg/ml (68.22-103.70 pg/ml)], the euthyroid, LT4-CAIH group [125.71 pg/ml (106.11-149.48 pg/ml)] had significantly higher levels of sFasL (P < 0.0001). In a chronological study, there was no significant correlation between sFas, sFasL, and the duration of levothyroxine therapy. In conclusion, normalization of serum sFas and sFasL levels cannot be achieved during levothyroxine treatment in patients with CAIH. It appears that levothyroxine therapy has no important effect on down-regulation of apoptotic factors in CAIH. Thus, like thyroid autoantibodies, monitoring of serum levels of sFas/sFasL is not indicated during thyroid hormone therapy.

Osteoprotegerin in relation to type 2 diabetes mellitus and the metabolic syndrome in postmenopausal women.

Osteoprotegerin (OPG) is an inhibitor of bone resorption. Circulating levels of OPG seem to be elevated in patients with cardiovascular disorders and diabetes. The relationship between OPG and the metabolic syndrome has never been studied in postmenopausal women. In a population-based study, 382 Iranian postmenopausal women were randomly selected. Cardiovascular risk factors, high-sensitivity C-reactive protein, and OPG were measured. The diabetes classification and the metabolic syndrome definition were based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. The mean serum OPG level was higher in those with type 2 diabetes mellitus than those without diabetes (4.33 +/- 1.70 vs 3.84 +/- 1.76 pmol/L, P = .016). In multiple logistic regression analysis, type 2 diabetes mellitus showed a significant association with serum OPG levels when adjustments were made for age, high-sensitivity C-reactive protein, and cardiovascular risk factors (odds ratio = 2.21; confidence interval, 1.34-3.66; P = .002). No significant difference was found between the mean serum OPG levels of those with the metabolic syndrome and those without the metabolic syndrome. Mean OPG levels did not differ significantly between subjects with and without hypertension, dyslipidemia, glucose intolerance, or abdominal obesity according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. In conclusion, circulating OPG levels are significantly associated with diabetes, independent of cardiovascular risk factors in postmenopausal women. However, OPG levels have no correlation with the metabolic syndrome or its components. Further studies are warranted to determine the pathophysiologic origin of elevated OPG in type 2 diabetes mellitus.

Relationships among serum receptor of nuclear factor-kappaB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineral density in postmenopausal women: osteoimmunity versus osteoinflammatory.

OBJECTIVE: The aim of this study was to investigate the correlations among circulating osteoprotegerin (OPG), the receptor activator of nuclear factor-kappaB ligand (RANKL), high-sensitivity C-reactive protein (hsCRP), and bone mineral density (BMD) in healthy postmenopausal women. METHODS: In a population-based study, highly specific enzyme-linked immunosorbent assay methods were used to evaluate the sera of 382 healthy Iranian postmenopausal women (mean age +/- SD, 58.7 +/- 7.5 y) for RANKL, OPG, hsCRP, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. RESULTS: Circulating levels of OPG (r = 0.30, P < 0.001) and the RANKL/OPG ratio (r = -0.17, P < 0.001) were significantly associated with age. The geometric mean of hsCRP was 1.89 mg/L (SE, 1.05) in the population studied. There was a significant correlation between log(hsCRP) levels and body mass index (BMI; r = 0.36, P < 0.001). Multivariate linear analyses revealed that age (beta = -0.295, P < 0.001), BMI (beta = 0.464, P < 0.001), RANKL (beta = -0.105, P = 0.014), and OPG (beta = 0.098, P = 0.029) were the independent determinants for lumbar BMD (R(2) = 0.35). Age (beta = -0.250, P < 0.001), BMI (beta = 0.486, P < 0.001), and RANKL (beta = -0.110, P = 0.009) were independently correlated with femoral neck BMD (R(2) = 0.36). Age- and BMI-adjusted analysis by quartiles of log-transformed hsCRP did not reveal an association with BMD, serum levels of biochemical markers of bone turnover, RANKL, or OPG. CONCLUSIONS: The circulating levels of the RANKL/OPG osteoimmunity system have an association with BMD, but subclinical systemic inflammation may not be involved in bone mass in healthy postmenopausal women.

High sensitivity C-reactive protein is associated with the metabolic syndrome independent to viral and bacterial pathogen burden.

AIM: To investigate the influences of bacterial or viral pathogen burden in the relationship of high sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome in a population-based study. METHODS: Data from 1754 men and women aged >or=25 years, from the Persian Gulf Healthy Heart Study were analyzed. The definition of the metabolic syndrome according to the Adult Treatment Panel III was used. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, Herpes simplex virus type 1, Helicobacter pylori and cytomegalovirus using ELISA. Measurement of CRP by a high-sensitivity CRP assay was done. RESULTS: The subjects with the metabolic syndrome had a higher geometric mean of CRP levels than the normal persons (p<0.0001). A linear relationship between an increase in the number of metabolic syndrome components and CRP concentrations was observed (p for trend<0.0001). In multiple logistic regression models, hs-CRP showed significant associations with the metabolic syndrome after controlling for cardiovascular risk factors and infectious burden divided into 2, 3 and 4 pathogens [OR=2.06, CI (1.32-3.21), p=0.001; OR=1.75, CI (1.26-2.42), p=0. 001; OR=2.12, CI (1.46-3.08), p<0.0001; respectively]. CONCLUSION: There was a strong association between inflammation and the metabolic syndrome independent to viral and bacterial infectious burden.

Elevated high sensitivity C-reactive protein is associated with type 2 diabetes mellitus: the Persian Gulf Healthy Heart Study.

Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. However, limited information is available about the relationship of diabetes mellitus and inflammation in Asia. We examined the association between high-sensitivity C-reactive protein (CRP) levels and diabetes in a general Iranian population. In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged > or = 25 years, a random sample of 1754 (49.2 percent males, 50.8 percent females) subjects were evaluated. High sensitivity C-reactive protein was measured by enzyme-linked immunosorbent assay. Elevated serum CRP was defined as more than 3.0 mg/l. The diabetes classification was based on the criteria of the American Diabetes Association. A total of 8.6 percent of the subjects (8.0 percent of males & 9.1 percent of females; p>0.05) had type 2 diabetes mellitus. Geometric mean of CRP was 1.94 mg/l (3.80 SD) in the studied population. The subjects with diabetes had a higher geometric mean of CRP levels than the subjects with no diabetes [3.67 (SD 3.71) versus 1.85 (3.83) respectively; p<0.0001)]. In multiple logistic regression analysis, diabetes showed a significant age-adjusted association with elevated CRP levels [Odds Ratio = 2.03, Confidence Interval (1.38-2.98); p<0.0001] after adjusting for sex, LDL-cholesterol, HDL-cholesterol blood pressure, smoking and body mass index. In conclusion, beyond traditional cardiovascular risk factors, elevated CRP is significantly correlated with diabetes in general population of the northern Persian Gulf. Further insight into the specific effects of proinflammatory cytokines and acute-phase proteins will be essential for the development of new preventive strategies for diabetes mellitus.

Relationship among insulinlike growth factor I concentrations, bone mineral density, and biochemical markers of bone turnover in postmenopausal women: a population-based study.

OBJECTIVE: : To assess the association among serum insulinlike growth factor I (IGF-I) concentrations, bone mineral density (BMD), and biochemical markers of bone turnover in a large group of postmenopausal women from the general population. DESIGN: : As an extension of a larger epidemiological study, the Iranian Multicentral Osteoporosis Study, a total of 406 healthy postmenopausal women (age, 59.0 +/- 7.6 years) were randomly selected from 13 clusters in Bushehr Port. IGF-I, serum CrossLaps, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific enzyme-linked immunosorbent assay. BMD was determined for the lumbar spine (L2-4) and proximal femur using dual-energy x-ray absorptiometry. RESULTS: : The mean (+/- SD) serum IGF-I concentration for all postmenopausal women was 183.35 +/- 65.60 ng/mL. In age-adjusted analyses, there was no correlation between IGF-I and BMD at the lumbar spine and femoral neck. Compared with women in the lowest quartile of IGF-I, women in the highest quartile had a significantly greater means of osteocalcin (P = 0.04) and alkaline phosphatase (P = 0.01). Analysis by quartiles of IGF-I did not reveal an association with serum CrossLaps. CONCLUSIONS: : Circulating IGF-I is associated with biochemical markers of bone formation, but there is no relationship among IGF-I, degradation products of C-terminal telopeptides of type I collagen, and BMD in postmenopausal women. Clearly more work will be needed before serum IGF-I can be used in clinical practice as a risk predictor for postmenopause-associated loss of bone mass.

Correlation of hyperhomocysteinaemia and Chlamydia pneumoniae IgG seropositivity with coronary artery disease in a general population.

BACKGROUND: Both Chlamydia pneumoniae infection and hyperhomocysteinaemia have been assumed to increase the atherosclerotic risk independently of each other and independently of the classic risk factors. The correlation between hyperhomocysteinaemia, C. pneumoniae infection and coronary artery disease (CAD) have not been investigated in the general population. METHODS: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of men and women aged >or=25 years, a random sample of 1699 (48.9% males, 51.1% females) subjects were evaluated. Total homocysteine, high sensitivity C-reactive protein (CRP) and IgG antibodies to C. pneumoniae were determined by ELISA. Minnesota coding criteria of a 12-lead resting electrocardiogram was used for evaluation of CAD. RESULTS: A total of 12.4% of the subjects had electrocardiogram-defined (Minnesota-coding criteria) coronary artery disease. Hyperhomocysteinaemia (>14 micromol/l) and IgG seropositivity were found in 50.8% and 37.7%, respectively. Neither of hyperhomocysteinaemia nor C. pneumoniae IgG seropositivity showed a significant association with CAD after adjusting of sex and age. Concurrent elevated CRP level (>8.2mg/l) and C. pneumoniae seropositivity (chronic C. pneumoniae infection) had a significant association with CAD [OR=1.73, CI (1.09-2.75); p=0.01] after adjusting for age, sex, systolic and diastolic blood pressures, BMI, and serum levels of LDL-cholesterol, fasting blood sugar and triglyceride as covariates in a logistic regression model. This odds ratio increased to 2.11, CI (1.18-4.12; p=0.02) when concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single covariate entity; was adjusted for multiple risk factors in another logistic regression model. CONCLUSION: Concurrent hyperhomocysteinaemia and chronic C. pneumoniae infection, as a single entity, was independently associated with coronary artery disease in the general population. This synergism may have important implications for risk-stratification and intervention trials.

The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: the Persian Gulf Healthy Heart Study.

BACKGROUND: The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated. METHODS: In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori) and CMV using ELISA. RESULTS: In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05-3.10); p = 0.03], H. pylori [OR = 1.50 (1.12-2.00); p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27-2.25); p < 0.0001] showed a significant association with the metabolic syndrome in men and HSV-1 [OR = 1.95 (1.22-3.11); p = 0.005], H. pylori [OR = 1.45 (1.09-1.94); 0.01] and Chlamydia pneumoniae [OR = 1.65 (1.23-2.21); p = 0.001] in women. CONCLUSION: The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.