Association of different lipid measures with incident bone fractures: Tehran lipid and glucose study.

OBJECTIVE: To investigate the association between different lipid measures and long-term hospitalization-required incident fracture among Iranian men and women. METHODS: A total of 3309 individuals aged ≥50 years (men = 1598) were included in the study. Multivariate Cox proportional hazard analyses were performed to assess the risk of incident fracture across quintiles, considering first quintile as reference, as well as for 1-standard deviation (SD) increase in each lipid measure, i.e. total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and related indices (TG/HDL-C and TC/HDL-C). Covariates included age, body mass index, current smoking, type 2 diabetes mellitus, hypertension, lipid lowering-drugs, and steroid medications (for women). RESULTS: During a median follow-up of 18 years, incident fracture was observed in 201 cases (men = 87). In both gender, no linear association was found between different lipid measures and incident fracture. Among men, only the fourth quartile of TG was associated with lower risk of fracture in the age-adjusted analysis with the hazard ratio (HR) and 95% confidence interval (CI) of [0.45 (0.21-0.95)]. Among women, the age-adjusted HRs and 95% CIs for the second, third, fourth, and fifth quintiles of non-HDL-C were [0.46 (0.25-0.87)], [0.73 (0.42-1.25)], [0.90 (0.54-1.51)], and [0.52 (0.29-0.95)], respectively; the corresponding values in the multivariate model were [0.48 (0.26-0.90)], [0.76 (0.4-1.32)], [0.94 (0.56-1.58)], and [0.52 (0.28-0.95)], respectively. The second quintile of LDL-C was also associated with lower risk for incident fracture in the multivariate analysis [0.53 (0.29-0.98)]. CONCLUSIONS: Among Iranian women, a nonlinear association between non-HDL-C and LDL-C and incident fracture was found as the second and fifth quintile of the former and the second quintile of the latter were associated with about 50% lower risk of fracture. Generally, our findings did not support harmful impact of these lipid measures on incident fracture.

Impact of educational level on incident chronic kidney disease during 13 years of follow-up: a prospective cohort study.

OBJECTIVES: To examine the association between educational level and chronic kidney disease (CKD) among the Iranian population. STUDY DESIGN: This is a prospective cohort study conducted in the framework of the Tehran Lipid and Glucose Study. METHODS: A total of 8173 Iranians (men = 3659) aged ≥20 years were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The association between educational status and CKD was explored using multivariate Cox proportional regression analyses, adjusted for age, gender, current smoking, marital status, body mass index, waist circumference, baseline eGFR, diabetes, hypertension, physical activity, history of cardiovascular diseases and dyslipidaemia. RESULTS: During a median follow-up of 13.14 years, 2609 cases of incident CKD were identified; the corresponding incidence rate was 26.35 (range 25.39-27.34) per 1000 person-years. Compared to low educational level, middle and high educational levels showed lower risks for incident CKD in the crude model [hazard ratio (HR) 0.37 (95% confidence interval {CI} 0.34-0.40) and HR 0.40 (95% CI 0.35-0.45), respectively]; however, these HRs changed direction after further adjustment for age and gender [HR 1.26 (95% CI 1.14-1.39) and HR 1.40 (95% CI 1.22-1.61), respectively]. The increased risk of incident CKD for those at higher educational levels remained significant in the fully adjusted model. In addition, results from the gender stratified analyses were in the same direction as those found among the whole study population (P-value for interaction of gender and education >0.8). CONCLUSIONS: Higher educational levels were associated with incident CKD during more than a decade of follow-up; this finding may be attributed to unhealthy lifestyle behaviours among this population group.

Iodine supplementation for pregnant women: a cross-sectional national interventional study.

BACKGROUND: Although Iran has been considered iodine replete since 2000, the first national survey of iodine intake among Iranian pregnant women in 2014 indicated that despite the adequate intake of iodine by the general population, this vulnerable group has moderate iodine deficiency. Therefore, in this national cross-sectional interventional study, we aimed to assess the iodine intake and thyroid function of Iranian pregnant women 2 years after implementing national iodine supplementation for this vulnerable group. MATERIALS AND METHODS: In this cross-sectional study, we conducted a national interventional survey of pregnant women. A total of 1200 pregnant women (400 women from each trimester) from 12 provinces of Iran were recruited from the antenatal care clinics from October 2018 to March 2019. The median urinary iodine concentration (MUIC), as an indicator of iodine status in three spot urine samples, was measured, along with the serum total T4 (TT4), thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPO-Ab), and iodine content of household salt. RESULTS: The mean age of the cohort was 28 ± 6.2 years, with the mean gestational age of 22.7 ± 13.0 weeks. The overall MUIC (IQR) of pregnant women was 188 µg/L (124.2-263 µg/L). Also, the MUICs in the three trimesters of pregnancy were 174 µg/L (110-254), 175 µg/L (116-251), and 165 µg/L (114-235), respectively. The MUICs ≥ 150, 100-149, and < 100 µg/L were found in 63, 19.8, and 16.2% of the subjects, respectively. The mean TT4 level was 12 ± 4.5 µg/dL, and the median (IQR) level of TSH was 2.37 mIU/L (1.66-3.18 mIU/L). According to our local reference range, 118 (10.5%) pregnant women had subclinical hypothyroidism, 6 (0.53%) women had isolated hypothyroxinemia, and 65 (5.7%) women were TPO-Ab positive. Also, the median (IQR) level of Tg was 10.08 µg/dL (5.7-20.4 µg/dL), and the median iodine content of household salt was 29.6 µg/g; the iodine content was ≥ 30 µg/g in 85% of household salt. The results showed that more than 95% of households were under iodized salt coverage. CONCLUSION: The results of this study indicated that iodine supplementation with at least 150 µg of iodine per day improved the iodine intake of pregnant women. Except for subclinical hypothyroidism, the prevalence of clinical hypothyroidism, clinical/subclinical thyrotoxicosis, TPO-Ab positivity, and isolated hypothyroxinemia decreased significantly, which emphasizes the importance of iodine supplementation during pregnancy.

All-cancer incidence in Tehranian adults: more than a decade of follow-up-results from the Tehran Lipid and Glucose Study.

OBJECTIVES: To investigate the incidence rates for different malignancies and assess the risk factors for all-cancer incidence in Tehran. STUDY DESIGN: Cohort study. METHODS: This study consists of 8599 participants aged ≥ 30 years who were free of cancer (3935 men). Cancer diagnosis was based on pathology reports. Sex-stratified crude incidence rates and age-standardized incidence rates (ASRs) using Segi's method were calculated for all-cancers. Multivariate Poisson regression models were used to evaluate associations of potential risk factors, including sex, age, obesity status (body mass index [BMI]: 25-30 kg/m2 as reference), education, smoking status, and diabetes mellitus with the incidence of cancers among the population. Incidence rate ratios (IRRs) with 95% confidence interval (CI) were also reported. RESULTS: During a median follow-up of 13.9 years, there were 130 and 129 incident cancers for men and women, respectively; the corresponding ASRs were 356.1 and 243.6 per 100,000 person-years, respectively. The three most incident cancers among men were gastrointestinal (GI) (ASR = 127.5), hematopoietic (ASR = 99.5), and reproductive system malignancies (ASR = 46.3). The most common incident cancers in women were breast cancer (ASR = 92.1), GI (ASR = 65.4), and reproductive system malignancies (ASR = 16.8). Among risk factors for cancer incidence, age (IRR [95% CI]: 1.05 [1.03-1.06]) and having a BMI < 25 kg/m2 (IRR [95% CI]: 1.38 [1.01-1.90]) had a statistically significant association with incident cancer. CONCLUSIONS: The high rates of cancers in Tehran during more than a decade of follow-up calls for a need to define risk factors as well as to implement programs for early screening.

The association between serum total testosterone and progression of hyperglycemia: a 15-year prospective cohort study.

BACKGROUND: The association between low testosterone concentration and increased risk of hyperglycemia in men has been demonstrated in observational and interventional studies. However, considering a variety of confounding factors, limited population-based studies have so far been conducted. Also, no information is available regarding the effect of testosterone on progressive development of dysglycemia. OBJECTIVE: To examine the effect of total testosterone on development of pre-diabetes/diabetes in normoglycemic middle-aged and older men. MATERIALS AND METHODS: Data were obtained from the Tehran Lipid and Glucose Study, a community-based prospective cohort of an Iranian population. Analyses were conducted on 903 normoglycemic eligible men aged 30-70 years. An illness-death model was applied to estimate the probabilities of three transitional phases of normoglycemia→diabetes, normoglycemia→pre-diabetes, and pre-diabetes→diabetes. RESULTS: Over a median follow-up of 12 years, 0.9% individuals developed diabetes. Per unit increase (ng/mL) in testosterone concentration, the transition rate from normoglycemia to pre-diabetes decreased by 6% [hazard ratios (HRs): 0.94 (95% confidence interval (CI): 0.90, 0.99)]. However, no effect for testosterone on the progression of diabetes from normoglycemia or pre-diabetes was observed [HRs: 0.79 (95% CI: 0.44, 1.41) and 0.98 (95% CI: 0.84, 1.16), respectively]. High body mass index was a strong predictor of hyperglycemia within all transitions. DISCUSSION: Independent of major confounding factors, low testosterone was associated with normoglycemia progression to pre-diabetes, but not with pre-diabetes to diabetes, which might indirectly highlight the stronger impact of other risk factors after occurrence of pre-diabetes. CONCLUSION: Low testosterone concentrations in men are associated with progression from normoglycemia to pre-diabetes, but not from pre-diabetes to diabetes.

Thyroid dysfunction in patients with impaired glucose metabolism: 11 year follow up from the Tehran Thyroid Study.

OBJECTIVES: This study aimed to assess the prevalence and incidence and predictive factors of thyroid disorders (TD) in patients with impaired glucose metabolism. METHODS: Prevalence of TD was calculated in patients with impaired glucose metabolism compared to healthy controls, aged over 30 years in phase 1 of the Tehran Thyroid Study (TTS). Follow up assessments were conducted every 3 yrs, after which incidence of TD was calculated and its correlations with age, sex, smoking, blood pressure, body mass index (BMI), thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides and cholesterol were assessed. RESULTS: Incidence of TD among 435 diabetics, 286 prediabetics, and 989 healthy controls at baseline was 14, 18, and 21 per 1000 patients per year, respectively, being significantly lower in diabetics than that in healthy controls, a difference however that was not significant after adjusting for the variables mentioned (OR:0.64, 95% CI: 0.39-1.01). The incidence of TD in subjects with baseline serum TSH>1.94 mU/L or TPOAb≥40 IU/ml in all three groups was higher than that in patients with TSH≤1.94 mU/L or TPOAb<40 IU/ml, and remained significant after variable adjustment. Baseline TSH>1.94 mU/L was predictive of TD with 70% sensitivity and specificity. Baseline serum TSH (ROC area: 0.73, 95% CI: 0.68-0.77) had better predictive value than TPOAb (ROC area: 0.65, 95% CI: 0.61-0.69) for developing TD. CONCLUSION: Incidence of TD in type 2 diabetics or prediabetics is not higher than healthy controls. It is however necessary to conduct thyroid tests in patients with TPOAb≥40 IU/ml or TSH>1.94 mU/L.

Is the association between insulin resistance and diabetogenic haematopoietically expressed homeobox (HHEX) polymorphism (rs1111875) affected by polycystic ovary syndrome status?

Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P<0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33-0.78; P=0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status.

Sex-specific incidence rates and risk factors of insulin resistance and ß-cell dysfunction: a decade follow-up in a Middle Eastern population.

AIMS: To examine the incidence of and risk factors for insulin resistance and ß-cell dysfunction in a representative Iranian population over a median follow-up of 9.2 years. METHODS: In total, 3662 people (1528 men) without known diabetes with a baseline homeostasis model assessment of insulin resistance (HOMA-IR) level < 75th percentile and, when ß-cell dysfunction was the outcome of interest, 3664 people (1530 men) with a homeostasis model assessment of ß-cell function (HOMA-ß) level ≥ 25th percentile were included in the study (HOMA-IR < 2.20 and HOMA-ß ≥ 64.3 among men, and HOMA-IR < 2.39 and HOMA-ß ≥ 81.7 among women). RESULTS: The incidence rates of insulin resistance and ß-cell dysfunction were 56.3 and 33.6/1000 person-years among men and 48.6 and 50.3/1000 person-years among women, respectively. Applying multivariable Cox regression in both sexes, fasting insulin, triglyceride/HDL cholesterol ratio and lower education were positive predictors of insulin resistance, whereas age was a negative predictor. Moreover, fasting plasma glucose, waist-to-height ratio, wrist circumference and lower hip circumference were significantly associated with incident insulin resistance only among women (all P < 0.05). Considering ß-cell dysfunction in both sexes, age and fasting plasma glucose increased the risk, whereas 2-h post-challenge plasma glucose was a positive predictor only among men, and waist-to-height ratio and triglyceride/HDL cholesterol ratio were negative predictors only among women (all P < 0.05). CONCLUSIONS: Modifiable risk factors are related to the incidence of insulin resistance and ß-cell dysfunction, which can be prevented with proper strategies although the difference between men and women should be taken into account.

The effect of a single dose of vitamin D on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a randomized clinical trial.

AIMS: To assess whether a single parental dose of 25-hydroxy vitamin D [25(OH)Vit D] could improve glucose control and inflammation in type 2 diabetic patients (T2D) with ischemic heart disease (IHD). METHODS: A randomized, placebo-controlled, double-blind trial was performed on 95 patients (47-placebo and 48-vitamin D groups). Participants were randomized using a randomization table to a single dose of either vitamin D (300,000 IU, IM) or a matching placebo. Fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), 25(OH)Vit D and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 8 weeks. RESULTS: No significant differences in baseline values were noted between groups, except in HbA1c, which was lower in the placebo group. In the supplemented group, the level of serum 25(OH)Vit D increased (29.6 ± 20.8 vs. 44.5 ± 19.2 ng/mL) and those of FBS and HbA1c decreased significantly [186.5 ± 64.1 vs. 165.1 ± 58.5 mg/dL and 8.2 ± 2.0 % (66.3 ± 21.8 mmol/mol) vs. 7.7 ± 1.8 % (61.7 ± 20.0 mmol/mol), respectively] (all p < 0.05), and no changes, however, were observed in the placebo group. We also compared change of marginal means of outcome variables (HbA1c, FBS, 25(OH)Vit D and hs-CRP) from baseline between the vitamin D versus placebo group, using ANCOVA, adjusted for the baseline of each variable itself, season at study entry, age and body mass index. During trial, only HbA1c level decreased significantly [0.48 % (standard error: 0.17), p = 0.04]. No any adverse effect was seen. CONCLUSIONS: A single parenteral dose of vitamin D in T2D patients with IHD improved glycemic control, but not inflammatory status. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trial Registry. CLINICAL TRIAL NUMBER: ACTRN12614000529640.

Maternal Thyroid Function and Autoimmunity in 3 Trimesters of Pregnancy and their Offspring's Thyroid Function.

This study was performed to evaluate maternal thyroid dysfunction and autoimmunity during pregnancy and its correlation with thyroid function of offspring. In this cohort study, Serum TT4, TT3, T3U, TSH, TPOAb, and TgAb were measured. Serum samples of 120 pregnant women were collected during 3 trimesters as well as in 57 cord bloods, 69 neonates, 34, 37, and 36 infants aged 2, 4, and 6 months. Repeated measure and Pearson correlation test were used to compare thyroid hormone values and to assess the correlations, respectively. Main outcomes were correlations between thyroid hormones and antibodies in mothers and offspring. An increasing trend for TT3 (p for trend < 000.1) and TSH (p for trend 0.01) was found over the course of gestation. Among 120 mothers, 10 (8%) had subclinical hyperthyroidism and 18 mothers (15%) showed subclinical hypothyroidism. We found one hypothyroid (0.8%) and 3 hyperthyroid (2.5%) mothers during pregnancy. Correlations among maternal thyroid hormones were found but not with auto-antibodies. A positive correlation between maternal thyroid auto-antibodies in all trimesters with cord blood and neonates was found. Cord blood TSH had a good correlation with maternal TSH, but only in the first trimester (r=0.29, p<0.05). A positive correlation between neonatal TSH and maternal TT4 was found only in the third trimester (r=0.25, p<0.05). Subclinical hypothyroidism was the most common thyroid dysfunction in the pregnant women studied. The association between maternal auto-antibodies and thyroid hormones of offspring was observed mostly in the neonatal period and became weaker after one month of age.

The Association Between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study.

Several studies have shown an association between overt hypothyroidism and diastolic hypertension. Association between subclinical hypothyroidism and hypertension is a matter of debate. The aim of this study was to examine the association of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure with serum thyroid hormones levels in euthyroid subjects.Data from 4 756 individuals of the Tehran Thyroid study (TTS) without any previously known thyroid disease were analyzed. We divided participants based on TSH tertiles. Serum TSH and free T4 (FT4) concentration, systolic blood pressure (SBP), diastolic blood pressure (BPD) body mass index (BMI) were measured in all subjects.Among 5 786 individuals participated, 4 985 were euthyroid. After implementing exclusion criteria, 4 756 individuals remained of whom 2 122 (44.6%) were male and 2 634 (55.4%) were female. Multiple linear regression analysis revealed no association between TSH levels within reference ranges and blood pressure profile. No significant relationship was observed between TSH levels and systolic or diastolic blood pressure or the mean arterial pressure or pulse pressure in each tertile of TSH. There was a negative association between pulse pressure and TSH in the second tertile (r=- 0.066, p=0.009). Regression analysis showed that FT4 was significantly associated with systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure.No association was found between serum TSH and blood pressure profile in euthyroid subjects. Serum FT4 levels showed a positive association with blood pressure profiles.

Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort.

AIM: The association between insulin resistance and thyroid function in euthyroid subjects has not yet been clarified. This study aimed to investigate the association between thyroid function within the normal reference range and insulin resistance in participants of the Tehran Thyroid Study (TTS). METHODS: This cross-sectional study was conducted within the framework of the TTS. Of 5786 subjects aged ≥ 20 years, 2758 euthyroid subjects free of thyroid disorders, diabetes, chronic kidney disease and cardiovascular disease, and not taking steroids and lipid-lowering agents, were included. Serum concentrations of free thyroxine (FT4) and TSH were measured. The homoeostasis model assessment index for insulin resistance (HOMA-IR) was used to evaluate IR. RESULTS: On linear regression analysis, a negative association was found between serum FT4 levels and HOMA-IR in the model with age, smoking and physical activity (B = -0.09, P < 0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B = -0.06, P < 0.01). In addition, there was a positive association between serum TSH levels and HOMA-IR in both models [with age, smoking and physical activity (B = 0.07, P = 0.006), and age, smoking, physical activity and adjusted for WC (B = 0.05, P = 0.01)] that was not more significant on logistic regression analysis. In women, neither serum FT4 nor TSH levels were associated with HOMA-IR; the prevalence of IR decreased from 27.2 to 19.1 with increasing tertiles of FT4 only in men (P = 0.01). No significant differences were observed in HOMA-IR and its components between thyroid peroxidase antibody (TPOAb)-negative and -positive groups. Also, it was found that metabolically healthy but obese (MHO) subjects had higher levels of TSH than individuals who were MONW (metabolically obese but normal weight; P < 0.01). CONCLUSION: Low FT4 was independently associated with IR in healthy euthyroid Iranian men.

Presence of hypertension modifies the impact of insulin resistance on incident cardiovascular disease in a Middle Eastern population: the Tehran Lipid and Glucose Study.

AIMS: To examine the independent impacts of the homeostasis model assessment of insulin resistance (HOMA-IR) and the updated model (HOMA2-IR) on incident cardiovascular /coronary heart disease in a Middle Eastern population with a high prevalence of cardiovascular disease risk factors. METHODS: We examined 3777 Iranian people, aged ≥ 30 years, without history of cardiovascular disease and without use of antidiabetic medication at baseline. Both HOMA-IR and HOMA2-IR were log-transformed and categorized into quartiles. The multivariable Cox proportional hazard regression model, adjusted for traditional cardiovascular disease risk factors, was applied to examine the association between HOMA-IR/HOMA2-IR with incident cardiovascular/coronary heart disease, considering the lowest quartile as reference. RESULTS: During a median follow-up of > 10 years, 197 cardiovascular disease and 181 coronary heart disease events occurred. Among the covariates, we found a significant interaction between hypertension and HOMA-IR/HOMA2-IR for incident coronary heart/cardiovascular disease (all P ≤ 0.01). Among the population without hypertension, the risk of cardiovascular disease significantly increased in the second [hazard ratio 1.96 (95% CI 1.04-3.68)], third [hazard ratio 1.93 (95% CI 1.00-3.75)] and fourth [hazard ratio 2.34 (95% CI 1.15-4.75)] quartiles of HOMA-IR, and the risk of coronary heart disease increased significantly in the fourth quartile of HOMA-IR [hazard ratio 2.30 (95% CI 1.12-4.73)], but no significant association was detected between HOMA-IR and cardiovascular/coronary heart disease in the population with hypertension. Among the populations both with and without hypertension, no risk was found to be associated with HOMA2-IR quartiles however, a 1-unit increase in HOMA2-IR was associated with a significant risk of cardiovascular disease among the non-hypertensive group [hazard ratio 1.60 (95% CI 1.03-2.48); P = 0.03]. CONCLUSIONS: The presence of hypertension modified the impact of HOMA-IR/HOMA2-IR on incident cardiovascular/coronary heart disease. The presence of insulin resistance highlighted a significant and independent risk for cardiovascular disease/coronary heart disease only in the population without hypertension.

Relationship of hyperinsulinaemia, insulin resistance and ß-cell dysfunction with incident diabetes and pre-diabetes: the Tehran Lipid and Glucose Study.

AIMS: To examine the association of fasting insulin, insulin resistance and reduced ß-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance). METHODS: An Iranian population comprising 1532 men and 2221 women, aged ≥ 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and ß-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance. RESULTS: During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (≥ 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced ß-cell function as measured by homeostasis model assessment of ß-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and ß-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender. CONCLUSIONS: Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired ß-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor ß-cell dysfunction were associated with incident isolated impaired glucose tolerance.

Sex-specific relations between fasting insulin, insulin resistance and incident hypertension: 8.9 years follow-up in a Middle-Eastern population.

The purpose of this study was to investigate whether fasting serum insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and insulin-to-glucose ratio (IGR) were associated with incident hypertension. In a prospective study, 4093 Iranian participants (1725 men and 2368 women) without hypertension and known diabetes at baseline (1999-2001) were followed for a median of 8.9 years. Regular follow-up examinations were performed at 3-year intervals. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension adjusting for sex, and in sex-stratified models. During the study, 896 incident cases of hypertension (432 men and 464 women) were identified (total incident rate: 27.5 per 1000 person-years). In the multivariable models, serum insulin level, HOMA-IR and IGR were positively associated with hypertension incidence, adjusting for sex. In the sex-stratified analyses, after adjusting for potential confounders, women in the highest quartile of insulin, HOMA-IR and IG had a significantly higher incidence of hypertension, compared with those in the lowest quartile (HR: 1.7 (95% CI 1.26-2.30); HR: 1.80 (95% CI 1.31-2.40) and HR: 1.67 (95% CI 1.26-2.22), respectively); among men, these relations were also significant, until including waist circumference and body mass index in the models (HR: 1.17 (95% CI 0.85-1.62), HR: 1.25 (95% CI 0.91-1.73) and HR: 1.06 (95% CI 0.77-1.45), respectively). Higher fasting serum insulin levels, HOMA-IR and IGR were associated with incident hypertension among women, whereas these associations were not significant after adjusting for obesity measures in men.

Prevalence of hypothyroidism in patients with dyslipidemia: Tehran Thyroid Study (TTS).

Hypothyroidism is a relatively common endocrine disorder usually accompanied with changes in serum lipid profiles. The purpose of this study was to assess the association between dyslipidemia and hypothyroidism in a population-based study. In this cross-sectional study, 2,315 dyslipidemic patients, aged 20-90 years (mean age: 38.1 ± 13.2 years), were selected from among 5,760 participants of Tehran Thyroid Study and divided into 3 groups, the subclinical hypothyroid, overt hypothyroid, and euthyroid subjects, based on national reference ranges. Serum lipid profiles, free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured in all subjects. In subjects with dyslipidemia and nondyslipidemia, the prevalence of subclinical was 7% and 4.1%, respectively, and for clinical hypothyroidism 3% and 1.2%, respectively. In dyslipidemic subjects, the mean low density lipoprotein-cholesterol (LDL-C) levels differed significantly (p = 0.03) among the overt hypothyroid (144.3 ± 36.1), subclinical hypothyroid (129.3 ± 39.2), and euthyroid (132.7 ± 39.0) groups. In the overt hypothyroid group, mean total cholesterol level was higher than in the normal group, but not significant. There were no differences in median triglycerides (TG) and mean high density lipoprotein-cholesterol (HDL-C) levels among the 3 groups mentioned. After adjusting for age and sex, hypothyroidism was not related to elevated serum lipid profiles in patient with dyslipidemia. In conclusion, there is significant difference in the prevalence of subclinical and clinical hypothyroidism between nondyslipidemic and dyslipidemic subjects; after adjustment for age and sex the presence of dyslipidemia did not predict the presence of hypothyroidism.

Predictors of the incident metabolic syndrome in healthy obese subjects: a decade of follow-up from the Tehran Lipid and Glucose Study.

BACKGROUND/OBJECTIVE: There is limited data from long-term prospective studies on the natural course of metabolic syndrome (MetS) incidence in healthy obese phenotypes. The aim of this study was to determine the incidence and predictors of the MetS in healthy obese subjects without the MetS at baseline after a decade of follow-up. SUBJECTS/METHODS: In this prospective cohort study, 438 obese subjects free from MetS at baseline, aged ≥20 years, were selected from among the participants of the Tehran Lipid and Glucose Study and followed up for 10 years for development of MetS. Based on national data, central obesity was defined as waist circumference cutoff point of 89 cm for men and 91 cm for women. RESULTS: Initially, subjects had a mean age of 41.1 ± 11.8 years and a body mass index of 32.7 ± 2.7 kg/m(2). At the end of follow-up, the cumulative incidence (95% confidence interval) of MetS was 44.0 (36.8-51.1)%. In the multivariable analysis, the adjusted odds ratios of hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and insulin resistance for the development of MetS were 3.08 (1.39-6.79), 2.84 (1.26-6.42), 6.49 (3.18-13.25) and 2.87 (1.55-5.32), respectively. The area under receiver operating characteristic curve of all the components was significantly higher than various combinations of MetS components, except for the two models including combinations of three components, that is, triglycerides (TGs), HDL-C and fasting blood sugar, as well as, TGs, HDL-C and systolic blood pressure. CONCLUSIONS: Our findings demonstrate that MetS developed in nearly half of the individuals during the 10 years of follow-up. Predictors of MetS in healthy obese subjects may differ from the general population, and waist circumference does not have an independent role.

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.

Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines.

The presence of thyroid autoantibodies is relatively high in women of childbearing age. There is evidence that positive thyroperoxidase antibody even in euthyroid women may increase the risk of spontaneous and recurrent pregnancy loss and preterm delivery. However, the evidence is not enough to justify recommendation on the screening of pregnant women for thyroid autoantibodies or LT4 supplementation for reducing maternal or fetal complications. In this paper we reviewed the related evidence and compared the new guidelines of the American Thyroid Association and Endocrine Society with respect to the screening and management of positive thyroperoxidase antibody in euthyroid pregnant women. As there was no major contradiction or disagreement between the two guidelines, either one of two guidelines may be used by clinicians for the appropriate management of thyroid autoimmunity during pregnancy.

Non-linear association between 25-hydroxyvitamin D and the incidence of type 2 diabetes: a community-based nested case-control study.

AIMS: To examine the nature of the association between 25-hydroxyvitamin D [25(OH)D] and newly diagnosed type 2 diabetes. METHODS: Serum 25(OH)D concentrations were measured for 761 participants (aged 20-83 years) in the Tehran Lipid and Glucose Study, selected for a 1-to-3 nested case-control study. Cases were 191 cases of Type 2 diabetes diagnosed during a median follow-up of 3.6 years. A total of 570 participants were matched with these cases with regard to age, sex, BMI, and month of entering the study. Diabetes was defined according to the American Diabetes Association criteria, 2003. Serum 25(OH)D was measured using the enzyme immunoassay method. Odds ratios for Type 2 diabetes were obtained from conditional logistic regression models for tertiles of serum 25(OH)D concentrations [tertile-1: 2.82-11.02 (reference), tertile-2: 11.03-21.80, and tertile-3: ≥ 21.82 ng/ml]. The multivariate model was adjusted for age, sex, family history of diabetes, systolic blood pressure, triglyceride-to- HDL cholesterol ratio, waist-to-height ratio, lifestyle modification intervention, leisure time physical activity, and fasting plasma glucose at baseline. Non-linearity in the associations between baseline 25(OH)D and Type 2 diabetes, was examined by using restricted cubic splines. RESULTS: Unadjusted odds ratios (95% confidence intervals) of diabetes were 0.73 (0.74-1.13), 0.54 (0.34-0.85) for the second and third tertiles, respectively. Multivariate adjusted odds ratios were 0.47 (0.25-0.90) and 0.43 (0.23-0.82), respectively. Below the cutoff of ~ 10 ng/ml the risk of newly diagnosed Type 2 diabetes increased dramatically. DISCUSSION: It was found that 25(OH)D concentrations contributed to the Type 2 diabetes incidence rate in a non-linear fashion, with the risk beginning to increase sharply for values < 10 ng/ml.