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ObjectiveFew prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes.MethodsWe performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up.ResultsAmong 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88–1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82–1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87–1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88–1.29). The results were robust in all sub-group and sensitivity analyses.ConclusionsThis is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes.Significance statementEvidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future. Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes. Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses. Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

© 2019 American Society of Andrology and European Academy of Andrology 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.

Background/Aims: We aimed to evaluate the association between change in thyroid function tests within the euthyroid range and body mass index (BMI) in persons with normal weight at baseline. Methods: This study investigated 1,100 normal-weight euthyroid persons in a population-based cohort study, Tehran Thyroid Study. BMI was calculated and serum concentrations of thyrotropin (TSH) and free T4 (FT4) were assayed at baseline and after 10 years of follow-up. We evaluated the relationship between thyroid and obesity based on 2 definitions for outcome: (1) a binary outcome as BMI 2, and (2) a multinomial outcome as normal BMI, overweight, and obese. Results: A total of 569 women and 531 men, aged 36.3 ± 13.5 years, were included. Modified Poisson regression analysis for binary outcome, after adjustment for age, sex, smoking, and anti-thyroid peroxidase antibody status, revealed a negative association between delta serum FT4 and follow-up BMI (relative risk 0.55 [95% CI 0.37-0.80]) without any significant association between change in serum TSH and follow-up BMI. However, in multinomial logistic regression analysis, we found no relationship between delta serum FT4 or TSH and follow-up BMI categories, for either overweight or obese vs. normal-weight participants. Conclusions: In normal-weight euthyroid individuals, changes in serum concentrations of FT4, but not TSH, may contribute to change in body weight.

Background Data regarding the effects of dietary protein on modifying serum lipid and lipoprotein levels are controversial. In this study we have investigated the hypothesis whether dietary protein and protein to carbohydrate ratio could be related to subsequent changes in lipid profile in adults. Methods This 3-yaers follow-up_longitudinal study was conducted on a sample of participants (845 men and 1043 women, aged 19-70 years) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated semi-quantitative food frequency questionnaire. Anthropometric and serum lipid and lipoprotein levels were measured both at baseline (2006–2008) and after 3 years. Results After adjustment for potential confounding variables and dietary factors, the highest quartile energy intakes from protein was inversely associated with changes in total cholesterol (β= -6.5; 95% CI= -11.5, -1.5) and HDL-C levels (β= -6.7; 95% CI= -12.2, -1.4) in men during the follow-up. Increased proportion of energy intake from protein, compared to that of carbohydrate also had favorable effect on 3-years changes in triglycerides (β= -18.2; 95% CI= -36.7, -0.1) and total cholesterol (β= -8.4; 95% CI= -15.1, -1.8) in men. Higher dietary P/C ratio (median ≥ 0.23) was associated with a significant decrease in serum total cholesterol at 3-years follow-up in men with the higher intake of protein (median ≥ 13.4 % of energy). Conclusion Higher intakes of dietary protein and more importantly, higher proportion of energy intakes from protein, compared to carbohydrate, had favorable effects on modifying lipid levels during a 3-year follow-up.

Objectives: The aim of this study was to assess leisure time physical activity and its determinants among adults in Tehran. Methods: This cross-sectional study comprised adults (n = 7285), aged 20 years and older. The subjects were participants of the Tehran Lipid and Glucose Study between 2002 and 2004. Information on the number of days spent on different activities during a week and the time devoted to each activity on a typical day was recorded. In addition, each activity, weighted by its relative intensity, was referred to as a metabolic equivalent. Results: The prevalence of inactivity was 69.8% (95% CI: 68.7-70.8) in the whole population and 30.2% (95% CI: 27.2-33.1%) of men and 30.3% (95% CI: 27.7-32.8%) of women were considered as active. Leisure time physical activity less than 30 min/week was scored in 1590 (50.6%) men and 1803 (43.5%) women. The most frequent leisure time physical activity performed by men (96.1%) and women (95.2%) was walking. A negative association was observed in men between leisure time physical activity and increased work hours, older age, more cigarette smoking and higher body mass index (69.8% were overweight and 75.3% were obese; P < 0.05). Leisure time physical activity was more likely to be associated with high educational levels in men. In addition, there was a statistically significant relationship between physical inactivity and occupation in both men and women. Conclusions: The prevalence of physical inactivity among adults in Tehran was high. Leisure time physical inactivity was more likely to be associated with older age, more cigarette smoking, more working hours, and higher body mass index. Public health efforts are needed to improve people′s participation in physical activities in Iran.

Background: In Nov 2013, the instruction for controlling high cholesterol has been released by the American College of Cardiology (ACC) and the American Heart Association (AHA) which need to be assessed in the different communities. Methods: Of total 6275 individual aged 40-75 years who entered at the Tehran Lipids and Glucose Study from March 1999 to 20 March 2010 in first examination cycle, 5153 with the median follow-up of more than ten years were eligible to enter in this study. The 10-year risk of hard cardiovascular disease (Hard CVD) for Statin therapy based on ACC/AHA clinical guideline was calculated and this risk was calculated for each subgroup of the guideline who recommended for statin therapy comparing to the risk in individuals with prevalent CVD. Results: Of nearly 6.5 million urban population of Iran (according to the 1996 census) about 4 million individuals (2.55 million men and 1.4 million women) were eligible for statin therapy. With respect to the urban population growth from the 1996 to the 2011 census (about 2.5 percent increases) the number of individuals for receiving statin increased by 50% (5 million men and 3 million women). Also, the risk in non-diabetic men with calculated risk of 5-7.5% and diabetic women with calculated risk of

Background: Renal ischemia reperfusion (RIR) injury is a common clinical syndrome that affects renal function and significantly increases morbidity and mortality. Hydrogen sulfide (H2S) is an endogenously gaseous mediator that exhibits many cytoprotective effects. Recently, studies have shown that H2S have opposite effects in different doses. Therefore, in the current study we investigated the effects of H2S at different doses on renal function after induced renal ischemia reperfusion injury model. Methods: The present study is an experimental study in animals and was conducted in Tehran University of Medical Sciences in April 2014. Male Wistar rats were assigned to five main groups (n= 6): 1) Sham, 2) Ischemia reperfusion (IR), 3) Administration of 50 µmol/kg Sodium hydrosulfide (NaHS)+IR, 4) Administration of 75 µmol/kg NaHS+IR and 5) Administration of 125 µmol/kg NaHS+IR. Sham group underwent laparotomy without cross-clamping of renal pedicles. Renal ischemia (IR) was induced in rats by both renal arteries occlusion for 55 min followed by reperfusion. Rats in the NaHS groups received intraperitoneal injections of 50, 75, or 125 µmol/kg of NaHS 10 minutes before the onset of ischemia and immediately after the onset of reperfusion. After reperfusion, plasma was collected for functional evaluation. Results: Compared to the sham, IR animals demonstrated a significant rise in plasma creatinine and BUN levels. Rats in the low-dose NaHS treated groups (H50, H75) had improved renal function by significantly decrease of creatinine and BUN levels. However, treatment with a high-dose of NaHS increased the levels of plasma creatinine and BUN levels as compared with these indices in the IR group. Conclusion: Our study demonstrates that different doses of Sodium hydrosulfide (NaHS) can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury.

Background & Objectives: Studying several linked markers provides more information on locating disease genes locus by using genetic association analysis. The aims of this study were to introduce Multimarker Family Base Association Tests (FBAT-MM) and its Linear Combination (FBAT-LC) in multimarker genetic association analysis and to examine the association of selected microsatellites with HDL-C in an Iranian population. Methods: One hundred twenty five (125) families having at least one member with metabolic syndrome and at least two members with low HDL-C were selected from participants of the Tehran Lipid and Glucose Study (TLGS). Multimarker genetic association of HDL-C level with some microsatellites in the chromosomes 8, 11, 12, and 16 were examined using FBAT-MM and FBAT-LC methods.Results: The families consisted of 563 individuals (269 males and 294 females). FBAT-MM showed significant genetic association only between HDL-C and three microsatellites in Chromosome 11 (P