F. Azizi

Sustainability of a well-monitored salt iodization program in Iran: Marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt

Objective: Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households. Methods: Schoolchildren (7–10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7–10 yr old children were compared in 2001 vs 1999. Results: In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18–499) μg/l and in 1996 (no.=2917) was 205 (10–2300) μg/l (p<0.0001). In 2001 vs 1996, mean±SD for iodine salt content was 32.7±10.1 vs 33.0±10.2 ppm (p=0.68) in households and was 33.2±13.4 and 33.8±13.2 ppm (p=0.57) in factories, respectively. Among 7–10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999. Conclusions: After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

Changes in calcium, 25(OH) vitamin D3 and other biochemical factors during pregnancy

Introduction and aims: Calcium and vitamin D play major roles in calcium homeostasis and skeletal development, especially during pregnancy. This study was conducted to determine changes in calcium, 25 hydroxy [25(OH)] vitamin D3 and other biochemical factors (PTH, osteocalcin, alkaline phosphatase, magnesium, phosphorus) related to calcium homeostasis and bone turnover during pregnancy and compare the values to those of non-pregnant women. Materials and Methods: In a cohort study, 48 pregnant women, in their first trimester of pregnancy (12±2.7 weeks), from 5 prenatal care centers, and 47 non-pregnant women randomly selected from the Tehran Lipid and Glucose Study (TLGS) population were enrolled. These pregnant women were followed in their second (26±1.9 weeks) and third trimesters (37±3.2 weeks) of pregnancy. Samples were drawn from June 2002 to March 2003. Including criteria were healthy women with no background of disease. Women using photo protection and calcium and vitamin D supplementation were excluded. A questionnaire was used to obtain demographic information for both groups. Venous blood samples were taken after 12–14 h of overnight fasting to measure serum calcium, phosphorus, magnesium, alkaline phosphatase, PTH, 25 (OH) vitamin D3 and serum osteocalcin levels. The repeated measures analysis of variance and t-test were used for statistical analysis. Data were matched for age and weight in both the case (in the first trimester) and control groups. Results: Significant differences were found in the mean serum levels of osteocalcin and alkaline phosphatase between the three trimesters of pregnancy (p<0.001). Osteocalcin was significantly higher in the first trimester as compared to second and third trimesters of pregnancy. Alkaline phosphatase was significantly lower in the first trimester as compared to the second and third trimesters of pregnancy and their controls. There was also a significant difference in osteocalcin in the second and third trimesters and alkaline phosphatase in the first and third trimesters of pregnancy in comparison to the control group. The mean values of osteocalcin were 12.7±8.5, 8.1 ±6.9,5.6±5.0 and 13.9±7.9 ng/ml, respectively, and mean values for alkaline phosphatase were 115±38, 125±37, 174±61 and 134±35.0 Iu/l, respectively. In the first trimester, alkaline phosphatase was lower and osteocalcin was higher than in the second and third trimesters. In the first trimester of pregnancy, 20 and 40% of women had 25(OH) vitamin D3 <10 and <20 ng/ml, respectively, and 19% of women had serum calcium levels <8.6 mg/dl. Conclusion: 60% of women in the first trimester, 48% in the second and 47% in the third trimester had either severe or moderate vitamin D deficiency. It is recommended that the importance of calcium supplements with vitamin D in pregnant women be stressed for these individuals.

Lipid ratios and appropriate cut off values for prediction of diabetes: a cohort of Iranian men and women

BackgroundDyslipidemia is a risk factor for incident type 2 diabetes; however, no study has specifically assessed the lipid ratios (i.e. total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)/HDL-C) as predictors of diabetes. We aimed to compare the independent association between the different lipid measures with incident diabetes over a median follow up of 6.4 years in Iranian men and women.MethodThe study population consisted of 5201 non diabetic (men = 2173, women = 3028) subjects, aged ≥20 years. The risk factor adjusted odds ratios (ORs) for diabetes were calculated for every 1 standard deviation (SD) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Receiver operator characteristic (ROC) curve analysis was used to define the points of the maximum sum of sensitivity and specificity (MAXss) of each lipid measure as a predictor of diabetes.ResultWe found 366 (146 men and 220 women) new diabetes cases during follow-up. The risk-factor-adjusted ORs for a 1 SD increase in TG, TC/HDL-C and TG/HDL-C were 1.23, 1.27 and 1.25 in men; the corresponding risks in females were 1.36, 1.14, 1.39 respectively (all p < 0.05, except TC/HDL-C in females which was marginally significant, p = 0.07). A 1 SD increase of HDL-C only in women decreased the risk of diabetes by 25% [0.75(0.64-0.89)]. In both genders, there was no difference in the discriminatory power of different lipid measures to predict incident diabetes in the risk factor adjusted models (ROC ≈ 82%). TG cutoff values of 1.98 and 1.66 mmol/l; TG/HDL-C cutoff values of 4.7 and 3.7, in men and women, respectively, TC/HDL-C cutoff value of 5.3 in both genders and HDL-C cutoff value of 1.18 mmol/l in women yielded the MAXss for defining the incidence of diabetes.ConclusionTC/HDL-C and TG/HDL-C showed similar performance for diabetes prediction in men population however; among women TG/HDL-C highlighted higher risk than did TC/HDL-C, although there was no difference in discriminatory power. Importantly, HDL-C had a protective effect for incident diabetes only among women.

Systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for prediction of cardiovascular events and mortality in a Middle Eastern population

Abstract We compared systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) as independent predictors of cardiovascular disease (CVD), total and CVD mortality among an Iranian population. The study conducted among 5991 subjects aged ≥ 30 years without baseline CVD and antihypertensive medication. The mean of two measurements of SBP and DBP, in sitting position, was considered the subjects blood pressure. During a median follow-up of 8.7 years, 346 CVD and 157 deaths, 63 attributed to CVD, occurred. Hazard ratios (HRs) of each outcome were calculated for a one standard deviation (SD) increase in each blood pressure (BP) measures. In multivariate models, all BP measures were associated with increased risk of CVD regardless of age. In those aged < 60 years, SBP, DBP, PP and MAP were associated with total mortality (p < 0.05), but in subjects aged ≥ 60 years, only SBP and PP increased risk of total mortality significantly. In multivariate analyses, a 1SD increase in SBP, PP and MAP were associated with 35%, 31% and 28% increased risk of CVD mortality (p < 0.05). In terms of fitness and discrimination of models, DBP, PP and MAP were not superior to SBP. In conclusion, our findings provided further evidence from a Middle Eastern population, in support of SBP predictability for CVD events and CVD and all-cause mortality compared with other BP measures.

Age-specific serum anti-Müllerian hormone levels: estimates from a large population-based sample

Abstract Objective Despite the wide use of anti-Müllerian hormone (AMH) measurement as a clinical marker for assessment of ovarian reserve, a population-based estimate for its reference values is not available. In this study, we have estimated age-specific AMH levels in a large sample of fertile women directly selected from a general population cohort. Methods All women who were naturally fertile and aged 18–50 years with regular menstrual cycles were selected from the Tehran Lipid and Glucose Study cohort and their blood levels of AMH were measured. Centiles for AMH distribution were estimated according to the exponential–normal 3-parameter model. We repeated the analysis after including a subgroup of women aged 40–50 years who met all the eligibility criteria except having entered natural menopause after age 40 years (n = 141). Results A total of 1015 women entered the study. The mean age was 36.7 years (standard deviation 7.5 years) and the mean body mass index was 27.0 kg/m2 (standard deviation 4.6 kg/m2). A non-linear decline of serum AMH concentration with age was observed. Age-specific AMH levels for the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles were calculated. Results were reproduced after inclusion of 141 women aged 40–50 years who met all the eligibility criteria except having entered natural menopause after 40 years. Conclusion In this study, we have presented a nomogram of age-specific estimates of anti-Müllerian hormone in a large sample of naturally fertile women within the general population. This could help clinicians in more accurate individual interpretation of serum AMH levels in healthy women.

Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: a population based study.

Background: Current reference values for thyroid function tests are based on data from different ethnicities and geographical areas. The aim of the present study was to determine reference intervals for thyrotropin (TSH) and free T4 (FT4), based on the criteria of the National Academy of Clinical Biochemistry (NACB) in an Iranian population. Material and methods: This study was conducted within the framework of Tehran Thyroid Study (TTS), an ongoing prospective cohort of 5704 randomly selected individuals, age ≥20 yr. A total of 2199 individuals (43.3% male, 56.7% female), based on NACB criteria were included in this study. Reference limit analysis was performed for the negative thyroid peroxidase antibody (TPOAb) group. Results: After applying all exclusion criteria except TPOAb positivity (10.5%), data of 2459 participants remained for analysis. Of these, 953 (43.3%) were males and 1246 (56.7%) were females; the mean±SD age was 43.53±14.16 yr. The mean±SD and median+IQR for TSH were 1.77 mU/l ±1.24 and 1.46 (0.93–2.23) mU/l, respectively. The 2.5th and 97.5th percentiles TSH were 0.32 mU/l and 5.06 mU/l respectively. The mean±SD and median (IQR) for FT4 for all negative TPOAb subjects were 1.19±0.16 and 1.18 (1.08–1.31) ng/dl respectively. Conclusion: Reference ranges for thyroid function tests need to be derived from national databases. This study determined age and sex specific TSH and FT4 reference ranges in a Tehranian population, which could eventually enable clinicians to classify patients more appropriately.

Impact of hip circumference and height on incident diabetes: results from 6‐year follow‐up in the Tehran Lipid and Glucose Study

Diabet. Med. 28, 1330–1336 (2011)

Effect of menopause on cardiovascular disease and its risk factors: a 9-year follow-up study

Abstract Objectives To explore the cardiovascular risk attributable to menopausal status in a 9-year follow-up, population-based study. Method All middle-aged women who met our eligibility criteria were selected from the Tehran Lipid and Glucose Study cohort. Data were collected by face-to-face interviews, physical examination and biochemical assessments at 3-year intervals. The World Health Organization classification was used to define menopausal status. Cardiovascular events that occurred in the cohort were investigated by a panel of medical specialists. Results Based on menopausal status, there were no significant differences in cardiovascular disease after adjustment for age, body mass index and other confounders; however, significant relationships between serum concentrations of low density cholesterol and total cholesterol and menopausal status were observed. Conclusions Menopause, independent of other cardiovascular disease risk factors, incurred cardiometabolic risk.

Transient congenital hypothyroidism in an iodine-replete area is not related to parental consanguinity, mode of delivery, goitrogens, iodine exposure, or thyrotropin receptor autoantibodies.

Objective: To assess transient congenital hypothyroidism (TCH) etiologies in two Iranian cities. Materials and methods: Cord dried blood spot samples were collected from neonates in Tehran and Damavand. Serum TSH and T4 were measured in those with cord TSH ≥20 mlU/l. Normal serum values at 2–3 weeks of age confirmed transient hyperthyrotropinemia (THT), while persistently abnormal levels revealed congenital hypothyroidism (CH). Normal serum TSH and T4 4–6 weeks after levothyroxine replacement therapy discontinuation at 2–3 yr of age differentiatedTCH from persistent CH. Results: Among 50,409 screened newborns, 9 (1:5601 births) were diagnosed as TCH and compared to 88 full-term neonates (≥37 weeks’ gestation) with THT and 45 normal (cord TSH<20 mIU/l) neonates. At a median age of 11 days, median (range) serum TSH values in TCH, THT, and normal neonates were 36.8 (13–130), 3.6 (0.1–13.3), and 2.9 (0.7–8.0) mIU/l (p<0.0001) and serum T4 values were 97 (36–168), 142 (74–232), and 160 (79–228 nmol/l), respectively (p=0.002). Urinary iodine concentration (UIC) >220 μg/l was observed in 5 (55.6%) of TCH neonates. The occurrence of TCH was not associated with gender, parental consanguinity, mode of delivery, pre- or post-natal consumption of goitrogens and/or thyroid affecting medications, TSH receptor autoantibodies, or neonatal UIC. Conclusions: Elevated UIC was the most frequent finding in newborns with TCH but the distribution of excessive UIC was not significantly different among TCH, THT, and normal neonates. Since no other etiologies were found in TCH neonates without elevated UIC values, evaluation of other environmental and/or genetic factors is warranted.

Cardiovascular risk and all-cause mortality attributable to diabetes: Tehran Lipid and Glucose Study

Aim: To quantify the burden of cardiovascular diseases (CVD), and all-cause mortality attributable to diabetes. Subjects and methods: Data on an 8.6-yr follow-up of 6331 participants (2741 men), free of CVD at baseline, were analyzed to determine the burden of CVD and all-cause mortality attributable to self-reported and screen-detected diabetes mellitus (SRDM and SDDM, respectively). Risks of events of interest were separately assessed for women and men using Cox-proportional-hazard model. Results: The mean age at baseline was 47 yr with 997 (15.7%) of participants having diabetes (men 14.8%, women 16.5%). SRDM and SDDM prevailed in 9.7% (men 9.2, women 10.2%) and 6.0% of participants (men 5.7, women 6.3%), respectively. During follow up (52,404 person-yr), we observed 447 incident cases of CVD [387 had coronary heart disease (CHD)] and 209 deaths. Among men, participants with SDDM had increased relative hazard for all-cause mortality translated to a population attributable risk fraction (PAF) of 10.1%. Among women, SDDM was associated with CVD and CHD but not with all-cause mortality; so that 9.3% and 8.8% of CVD and CHD events were respectively attributable to the SDDM. If SRDM had been eliminated from the population, the incidences of CVD, CHD, and death would have decreased by 10.5, 9.5, and 17.3% in men; and 22.0, 24.2, and 17.8% in women, respectively. Conclusion: SDDM and SRDM have high PAF for all-cause mortality and CVD. Besides diabetes treatment and prevention, screening to detect undiagnosed diabetes should warrant high priority among the public health strategies to lower the incidence of CVD and mortality.