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.

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels.

OBJECTIVE: It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). METHOD: Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06-11.52]ng/ml versus 10.50 [4.30-20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0 µg/ml versus 20.66±8.12 µg/ml, p<0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30-0.79]; p=0.004 and OR=0.74, CI [0.67-0.82]; p<0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. CONCLUSIONS: The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs' increased risk of diabetes needs to be further elucidated.

Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus.

AIM: To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction. METHODS: Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. RESULT: Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71±0.93 ng/ml versus 2.69±2.02 ng/ml, p=0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452±0.254 ng/ml versus 0.409±0.275 ng/ml, p>0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR)=1.71, 95% confidence interval (1.30-2.25); p<0.0001]. CONCLUSION: The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group.

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.

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.

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.

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.

Reference database of CrossLaps and osteocalcin for a healthy Iranian population.

Markers of bone turnover are becoming an important tool for practitioners in the management of osteoporosis. Therefore, it is essential to establish a reference database of the markers before using them in various clinical settings. A total of 785 individuals (37% males, 63% females) without apparent or suggested abnormalities affecting bone mass were randomly selected from 13 clusters in Bushehr Port in southern Iran. The serum CrossLaps ELISA and the N-MID Osteocalcin ELISA were used for the quantitative measurement of CrossLaps and osteocalcin in sera. Bone mineral density was determined for the lumbar spines (L2-L4), proximal femur (neck), and forearm (the distal part) using dual-energy X-ray absorptiometry. Men had higher biochemical serum bone markers (P<0.0001). In women, there were progressive increases in serum CrossLaps after 30 years of age, peaking at >60 years. In men, serum CrossLaps levels were decreased progressively by increases in age, with the peak at 20 - 29 years. In women, there was a significant decrease in serum osteocalcin from 20 - 29 years to 30-49 years, followed by a progressive increases during 50 - 59 years, with the peak at >60 years. In men, the highest concentrations for serum osteocalcin occurred at 20 - 29 years. At all sites checked for bone mineral densitys, women in the high osteocalcin quartile had the lowest mean bone mineral densitys values, but women in the high CrossLaps quartile had the lowest mean bone mineral densitys at lumbar and radial sites. However, in men, bone mineral densitys values at neither site differed between the lowest and the highest quartiles of serum biochemical bone markers. We presented a five- year age-specific mean values of bone markers in a general healthy Iranian population. Only women in the high osteocalcin and CrossLaps quartiles had the lowest mean bone mineral densitys values at the lumbar and radial sites. Our results suggest that the significance of osteoclastic bone resorption or bone formation as a determinant of bone mineral densitys may depend on sex.

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.

Concurrent increased high sensitivity C-reactive protein and chronic infections are associated with coronary artery disease: a population-based study.

BACKGROUND: An elevated serum level of C-reactive protein (CRP) is an independent predictor of coronary artery disease (CAD). Chronic infections have also been implicated in the pathogenesis of CAD. AIMS: To investigate how concomitant chronic infection and CRP related to electrocardiogram-defined CAD in a general population. SETTING AND DESIGN: A population-based cross-sectional study, which was conducted in three Iranian ports in the northern Persian Gulf. MATERIALS AND METHODS: For evaluation of CAD, we used Minnesota coding criteria of a 12-lead resting electrocardiogram in 1,754 subjects, aged 25 years and over, selected by cluster random sampling. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae (C. pneumoniae), Herpes simplex virus type 1 (HSV-1), Helicobacter pylori (H. pylori) and cytomegalovirus (CMV) using ELISA. Measurement of CRP by a high-sensitivity CRP assay was done. STATISTICAL ANALYSIS: Multiple logistic regression analysis was used. RESULTS: None of the infectious agents (CMV, H. pylori, C. pneumoniae and HSV-1) showed a significant association with electrocardiogram-defined CAD after adjusting for sex and age. Elevated CRP levels did not show significant association with electrocardiogram-defined CAD independent of seropositivity to one of the four infectious agents, but concurrent elevated CRP levels (>10.0 mg/L) and anti-C. pneumoniae [OR = 1.68 (CI, 1.24-2.59; P=0.04)], H. pylori [OR = 1.98 (CI, 1.26-3.13; P=0.003)], CMV [OR = 1.66 (CI, 1.10-2.49; P=0.01)] or HSV-1 [OR=1.79 (CI, 1.18-2.72; P=0.006)] IgG antibodies were associated with prevalence of electrocardiogram-defined CAD in the general population, after adjustment for multiple risk factors, including age, sex and the components of the metabolic syndrome. CONCLUSIONS: Beyond traditional cardiovascular risk factors, concomitant chronic infection and elevated CRP are significantly correlated with electrocardiogram-defined CAD.

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.