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Aims: Whether coronary artery calcium (CAC) testing in younger individuals with metabolic syndrome (MetS) and diabetes mellitus (DM) helps predict cardiovascular disease (CVD) and death independent of traditional risk factors (RFs) remains less clear., Methods and Results: We pooled data obtained from 5174 individuals aged 38-55 years from the CARDIA (Coronary Artery Risk Development in Young Adults; n = 3047, year 20) and MESA (Multi-Ethnic Study of Atherosclerosis; n = 2127, Visit 1) studies who completed computed tomography of CAC. The mean age (SD) of participants (44.7% men) was 47.3 (4.2) years. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of CVD, coronary heart disease (CHD), and all-cause death. There were 1085 participants (21.0%) with prevalent CAC at baseline. A total of 461 (8.9%) had DM, 1025 (19.8%) had MetS without DM, and 3688 (71.3%) had neither condition. Over a median follow-up of 14.2 years, 256 (5.0%) participants died, and 304 (5.9%) CVD and 188 (3.6%) CHD events occurred. The CAC score was independently associated with incident CVD in those with DM (HR: 95% CI; 1.22: 1.08-1.38), MetS (1.18: 1.08-1.31), and neither condition (1.36: 1.26-1.46). The corresponding HRs for CAC ≥ 100 were 2.70 (1.25-5.83), 3.29 (1.87-5.79), and 6.30 (4.02-9.86), respectively. Similar associations for CHD and death were found. The impact of CAC ≥ 100 on CVD and CHD was lower in the presence of DM (P interaction < 0.05). The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels., Conclusion: Coronary artery calcium score is independently associated with cardiovascular events and death over nearly 15 years after screening at ages 38-55 years, with a less pronounced impact on CVD and CHD events in the presence of DM., Competing Interests: Conflict of interest: M.D.S. is on the scientific advisory boards of Amgen, Agepha, Ionis, New Amsterdam, Novartis, Precision BioScience, and Novo Nordisk, and is a consultant for Ionis, Novartis, Regeneron, Aidoc, and Shanghai Pharma Biotherapeutics. All other authors declare that they have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999-2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0-10.1) and 2.9 (2.6-3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36-5.98], 1.92 [1.11-3.31], 2.04 [1.09-3.80] and 1.42 [1.10-1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10-2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events., (© 2023. The Author(s).)

Background and Aims: We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study., Methods: 7190 participants (4049 women) aged 20-90 years with 2-5 eGFR data from examinations (2001-2005 to 2015-2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline., Results: During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6-202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05)., Conclusion: KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD.Key messages:Menopausal status may influence the relationship between cardiometabolic risk factors and KFD;The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients.The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention.

Background: Previous studies have reported an association between a significant decline in estimated glomerular filtration rate (eGFR) over time and an increased risk of cardiovascular disease (CVD). This study aimed to investigate the association between the eGFR slope and CVD among individuals with and without diabetes., Methods: This prospective cohort study was conducted within the Tehran Lipid and Glucose Study (TLGS) framework. We studied 6919 adults aged 20-70 years, including 985 with diabetes and 5934 without diabetes. The eGFR slope was determined based on repeated measurements of eGFR through linear mixed-effects models. A multivariable Cox proportional hazard model was employed to evaluate the association between eGFR slope, both in continuous and categorical form, and the risk of CVD., Results: The slopes of eGFR exhibited a bell-shaped distribution, with a mean (standard deviation (SD)) of -0.63 (0.13) and - 0.70 (0.14) ml/min per 1.73 m 2 per year in individuals with and without diabetes, respectively. During a median follow-up of 8.22 years, following the 9-year eGFR slope ascertainment period, a total of 551 CVD events (195 in patients with diabetes) were observed. Among individuals with diabetes, a steeper decline in eGFR slope was significantly associated with a higher risk of CVD events, even after adjusting for baseline eGFR, demographic factors, and traditional risk factors for CVD; slopes of (-1.05 to -0.74) and (-0.60 to -0.52) were associated with 2.12 and %64 higher risks for CVD, respectively, compared with a slope of (-0.51 to 0.16). Among individuals without diabetes, the annual eGFR slope did not show a significant association with the risk of CVD., Conclusion: Monitoring the eGFR slope may serve as a potential predictor of CVD risk in individuals with diabetes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: As a surrogate for all relevant risk factors, it is preferable to show trends in the mean cardiovascular disease(CVD) risk rather than to examine each risk factor trend separately., Objectives: Using national representative data, this study aimed to determine the changes in the World Health Organization (WHO) CVD risk during the last decade considering both laboratory and non-laboratory risk scoring., Methods: We used data from five rounds of the WHO STEPwise approach to surveillance surveys (2007-2016). In all, 62,076 (31,660 women) participants aged 40-65 years were included and their absolute CVD risk were calculated. The generalized linear model was performed to assess the trend of CVD risk in men and women, and also in diabetic and non-diabetic individuals., Results: We showed significant declining trends in the mean CVD risk in the laboratory (from 10.5% to 8.8%) and non-laboratory (10.1% to 9.4%) models in men. In women, a significant reduction was observed in the laboratory-based model (from 8.4% to 7.8%). The laboratory model showed a greater decrease in men than women (P-for interaction < 0.001) and in diabetic patients (from 16.1% to 13.6%) than non-diabetic individuals (from 8.2% to 7%) (p-for interaction = 0.002). The proportion of high-risk individuals (risk ≥ 10%) decreased from 40% in 2007 to 31.5% in 2016 in men and from 29.8% to 26.1% in women based on the laboratory-model., Conclusions: During the last decade, CVD risk had a significant decrease in men and women. The reduction was more evident in men and diabetic population. However, still, one-third of our population is considered high-risk., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

To examine the associations between long-term exposure to five major air pollutants including SO 2 , PM 10 , O 3 , NO 2 , and CO , and incident dysglycemia, impaired fasting glucose (IFG), and diabetes, separately. A total of 4254 (1720 men) normoglycemic individuals aged 20-69 years at baseline were followed from 2001 to 2018 every 3 years. To measure the long-term hazards of air pollutants for incident dysglycemia, the Weibull proportional hazards models for every 10-unit increment adjusted for diabetes risk factors were fitted. The air pollutants were put in the models in the form of averages of 1-, 2-, and 3-year periods. During a median follow-up of 12.2 years, we observed 1780 dysglycemia events. In contrast to NO 2 , the increase in SO 2 , O 3 , and PM 10 levels were significantly associated with a higher risk of dysglycemia and IFG in all time spans excluding PM 10 at 2 years. The largest hazard ratios for incident dysglycemia and IFG were attributable to PM 10 in 3 years (2.20 (95% CI 1.67, 2.89) and 2.08 (1.55, 2.80), respectively). Moreover, exposure to all the pollutants except NO 2 in 1 year (0.89 (0.80, 0.98)) had no significant associations with incident diabetes. There was a signal that younger (< 45 years) and never-smoker individuals were more predispose to dysglycemic effects of air pollution (all P for interactions > 0.03). Our findings suggested that long-term exposure to air pollution increased incident dysglycemia risk, the effect which was mainly attributable to IFG status., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the relationship between glucose intolerance statuses at baseline defined as normal glucose tolerance (NGT), pre-diabetes, newly diagnosed (NDM) and known diabetes mellitus (KDM) and all-cause hospitalization among Iranian men and women during 20 years of follow-up., Research Design and Methods: This study included 8,014 individuals (3,836 men) ≥30 years from the cohort of Tehran Lipid and Glucose Study. Incidence rate ratios (IRRs) and (95% confidence interval (95% CI) for three groups of pre-diabetes, NDM and KDM was estimated using the Negative Binomial regression model, considering NGT group as reference group. Regression models were adjusted for age, body mass index, hypertension, chronic kidney disease, and cardiovascular disease (CVD)., Results: Among men, compared with NGT group, those with pre-diabetes, NDM and KDM had higher incidence rate for hospitalization, with IRRs (95% CI) of 1.08 (0.96-1.20), 1.38 (1.20-1.57) and 1.96 (1.66-2.26), respectively, after adjusting for confounders. The corresponding values were 1.07 (0.96-1.17), 1.40 (1.21-1.59) and 2.07 (1.72-2.42) for women. Men with diabetes, generally had a higher rate of hospitalization for CVD rather than their female counterparts (IRRs: 1.46; 1.17-1.74). In patients with diabetes, the most common causes of hospitalization were macrovascular complications (i.e. coronary heart disease and stroke). Moreover, among the individuals with diabetes, those with poor glycaemic control (fasting plasma glucose (FPG) >10 mmol/l) had 39% higher rate of hospitalization than those with fair glycaemic control (FPG <10 mmol/l) (1.39; 1.12-1.65), adjusted for confounders., Conclusion: Pre-diabetes, NDM, and KDM were associated with increased hospitalization rates during long-term follow-up. Interventions such as lifestyle modification or pharmacological therapies aiming to slow down the pre-diabetes and fair control of diabetes might potentially decrease the rate of hospitalization.Key messagesNDM and KDM status both increased rate of all-cause hospitalization.CVD and T2DM complication were the most common cause of hospitalization among patients with diabetes.Hospitalization due to recurrent CHD was significantly higher in men with diabetes than their female counterparts.

Background: We investigated the impact of weight change on mortality in a population-based cohort setting., Methods: We conducted two weight measurements for 5436 participants aged ≥ 30 years with an approximate 3-year interval. Based on their weight change, we categorized participants to: > 5% weight loss, 3-5% weight loss, stable weight (± < 3%), 3-5% weight gain, > 5% weight gain. We followed participants for mortality annually up to March 20th 2018. We applied the multivariable Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for all-cause, cardiovascular (CV), and cancer mortality, considering stable weight as reference. The Cox models was adjusted for age, sex, educational level, body mass index, smoking status, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease (CVD) at baseline., Results: During a median follow-up of 14.4 years, 629 deaths (247 CV and 126 cancer deaths) have occurred. Over 5% weight loss and gain were associated with increased risk of all-cause mortality in multivariable analysis with HRs of 1.47 [95% CI: 1.17-1.85] and 1.27 [1.02-1.57], respectively; however, a 3-5% loss or gain did not alter the risk of all-cause mortality significantly. These significant risks for wight change > 5% were not modified by the presence of diabetes, obesity, and smoking status; however, the unfavorable impact of weight change on mortality events was more prominent in those older than > 65 years (P-value for interaction: 0.042). After excluding those with history of CVD, diabetes, and cancer during the weight measurements period, these associations significantly attenuated (HR: 1.29 [0.89-1.87] for > 5% weight loss and 1.12 [0.84-1.50] for > 5% weight gain). Additionally, a > 5% weight loss was also associated with about 60% higher risk for CV mortality (HR: 1.62 [1.15-2.28]), and a 3-5% weight loss was associated with about 95% higher risk of cancer mortality (HR: 1.95 [1.13-3.38])., Conclusions: Our findings showed a U-shaped association across weight change categories for all-cause mortality risk with over 5% weight gain and loss causing higher risk. Moreover, weight loss can have adverse impact on CV and cancer mortality events., (© 2022. The Author(s).)

Background: This study investigates the trajectory of the risk factors of prediabetes progression to overt diabetes., Methods: The study retrospectively investigated 1610 prediabetic individuals. The trajectory of metabolic indicators was investigated using the generalized estimated equation method with autoregressive working correlation structure through a linear model with the identity link function., Results: During 15 years of follow-up, the trajectories of metabolic risk factors changed from 3 years before diabetes occurrence for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG), 6 years for waist circumference (WC), 9 years for high-density lipoprotein cholesterol (HDL-C), and earlier for body mass index, triglyceride (TG), and TG:HDL ratio. It was shown that the differences in the trajectory of WC and HDL were stable after adjustment for other metabolic risk factors. The trajectories of FPG and 2hPG remained stable after considering multiple insulin resistance markers., Conclusions: Deterioration of metabolic risk factor status can be a predictor of diabetes many years before its occurrence, but the abrupt change in plasma glucose is evident 3 years before diabetes mellitus onset. It seems that the HDL-C and WC trajectories are two independent predictors for diabetes incidence. It was also found that when the rising trend in plasma glucose starts, preventive strategies to lessen insulin resistance might not be efficient., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: To investigate the population based incidence rate of chronic kidney disease (CKD) and its potential risk factors among Iranian diabetic adults during over 14 years of follow-up., Methods: Two different equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]) were applied for the calculating the estimated glomerular filtration rate (eGFR). Among a total of 1,374 diabetic Tehranian adults, 797 and 680 individuals were eligible for CKD-EPI and MDRD analyses, respectively. CKD was defined as eGFR lower than 60 mL/min/1.73 m2. Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CI) for all potential risk factors., Results: The incidence rates (95% CI) of CKD per 1,000 person-years were 43.84 (39.49 to 48.66) and 55.80 (50.29 to 61.91) based on CKD-EPI and MDRD equations, respectively. Being older, a history of cardiovascular disease, and having lower levels of eGFR were significant risk factors in both equations. Moreover, in CKD-EPI, using glucose-lowering medications and hypertension, and in MDRD, female sex and fasting plasma glucose ≥10 mmol/L were also independent risk factors. Regarding the discrimination index, CKD-EPI equation showed a higher range of C-index for the predicted probability of incident CKD in the full-adjusted model, compared to MDRD equation (0.75 [0.72 to 0.77] vs. 0.69 [0.66 to 0.72])., Conclusion: We found an incidence rate of more than 4%/year for CKD development among our Iranian diabetic population. Compared to MDRD, it can be suggested that CKD-EPI equation can be a better choice to use for prediction models of incident CKD among the Iranian diabetic populations.

The coronavirus infection is an evolving pandemic with high morbidity and mortality, especially in people with comorbidities. The case fatality rate (CFR) is 9.2% in the presence of diabetes, while it is 1.4% in those without any comorbidity. Diabetes is a prevalent disease globally; hence, healthcare professionals are highly concerned about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic progression. Current evidence does not support higher incidence of coronavirus disease 2019 (COVID-19) in people with diabetes (PWD). However, people with diabetes are considered high risk for developing complications. Optimal metabolic control is a challenging concept, especially in the presence of an acute and severe respiratory viral infection. In this consensus, we considered the challenging issues in management of patients with diabetes during the COVID-19 pandemic. The consensus covers various aspects of outpatient as well as inpatient care based on the current evidence., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

To determine levels of change in risk factors for cardiovascular disease among people with and without a previous diagnosis of diabetes from 2007 to 2016 in Iran. Data were obtained from five rounds of the World Health Organization STEPwise approach to Surveillance (STEPS) cross-sectional surveys. Participants were 7665 and 93,733 adults with and without known diabetes, respectively, aged 25-65 years. We used logistic and linear regressions to assess the trends of risk factors. Individuals with known diabetes compared to those without the condition, experienced greater reductions in mean levels of systolic blood pressure (3.0 vs. 0.5 mmHg among women and 3.9 vs. 1.6 mmHg among men), diastolic blood pressure (6.4 vs. 5.11 mmHg in women and 3.3 vs. 1.8 mmHg in men), and non-HDL cholesterol (42.4 vs. 27.2 mg/dL among women and 30.3 vs. 21.0 mg/dL among men) throughout these years. Men with diabetes also showed a greater reduction in the prevalence of daily cigarette smoking compared to their non-diabetic counterparts (7.3% vs. 2.3%). Fasting plasma glucose decreased among subjects with diabetes but increased among those without diabetes. Significant increases were observed in proportions who met goals for blood pressure, triglycerides, non-HDL cholesterol and LDL cholesterol in both groups; however, almost half of diabetic subjects did not achieve risk factor goals in 2016. Secondary prevention in diabetic patients was more effective than primary prevention in the general population; however, the rate of diabetic patients who met the designated goals for each risk factor was still suboptimal.

Aims: To investigate future diabetes in different abdominal obesity phenotypes during 12 years of follow-up., Methods: For this population-based cohort, 7982 adults without diabetes including 3533 men and 4449 women, aged ≥20 years were selected from the Tehran Lipid and Glucose Study. Abdominal obesity was defined according to the national cutoffs for waist circumference (WC). Metabolic health was defined as having ≤1 metabolic abnormality based on Joint Interim Statement (JIS) criteria other than WC. Participants were classified into 4 groups of abdominal obesity phenotypes: Metabolically healthy non-abdominal obese (MHNAO), metabolically healthy abdominal obese (MHAO), metabolically unhealthy non-abdominal Obese (MUNAO), and metabolically unhealthy abdominal obese (MUAO)., Results: In total, 1018 cases of incident diabetes occurred. Compared to the MHNAO phenotype, based on multivariate Cox regression models, diabetes risk was increased in all unhealthy phenotypes except the MUNAO phenotype in men. Regarding the association of the MHAO phenotype with incident diabetes, borderline statistical significance in men [HR 1.5 (95% CI: 1.0-2.36), p-value: 0.07] and statistical significance in women [HR 1.68 (95% CI: 1.08-2.6)] were detected., Conclusions: In addition to unhealthy phenotypes except the MUNAO phenotype in men, the MHAO phenotype is also associated with incident diabetes, highlighting the importance of preventive strategies in this subgroup of abdominally obese subjects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the effect of combinations of blood pressure and glucose tolerance status on cardiovascular and all-cause mortality. A total of 7619 participants aged ⩾30 years old were stratified to nine categories as follows: (1) normotension (NTN) and normal glucose tolerance (NGT) (reference group), (2) NTN and pre-diabetes mellitus (pre-DM), (3) NTN and DM, (4) pre-hypertension (pre-HTN) and NGT, (5) pre-HTN and pre-DM, (6) pre-HTN and DM, (7) HTN and NGT, (8) HTN and pre-DM and (9) HTN and DM. Cox proportional hazards were applied to calculate the multivariate hazard ratios (HRs) of different groups for outcomes. For all-cause mortality outcomes, prevalent cardiovascular disease (CVD) was also adjusted. In a median follow-up of 11.3 years, 696 CVD and 412 all-cause mortality events occurred. Among the population free from CVD at baseline (n=7249), presence of HTN was associated with increased risk of CVD, regardless of glucose tolerance status with HRs of 1.97 (95% confidence interval (CI), 1.49-2.61), 2.25 (1.68-3.02) and 3.16 (2.28-4.37) for phenotypes of HTN and NGT, HTN and pre-DM and HTN and DM for CVD, respectively; corresponding HRs for all-cause mortality were 1.65 (95% CI, 1.15-2.37), 1.69 (1.15-2.49) and 2.73 (1.80-4.14), respectively. Phenotypes of NTN and pre-DM (1.48; 1.03-2.14) and NTN and DM (2.04; 1.06-3.92) were also associated with CVD and all-cause mortality, respectively. HTN was significantly associated with CVD/mortality events, regardless of glucose tolerance status. Blood pressure <120/80 mm Hg among pre-diabetic/diabetic population, not on antihypertensive medications, was generally associated with worse outcomes.

To evaluate the joint effect of hypertension (HTN) and diabetes (DM) on coronary heart disease (CHD), and stroke event, all-cause, and cardiovascular disease (CVD) mortality in Middle Eastern older adults, 2747 people (1436 women) aged ≥ 50 years, free of CVD at baseline, were categorized into four groups (HTN-/DM-, HTN+/DM-, HTN-/DM+, HTN+/DM+). Multivariate Cox proportional hazard models were run for different outcomes. To compare the impact of HTN versus DM, HTN+/DM- was considered as reference. In a median of 13.9 years, incidence rate of CHD, and stroke event, all-cause and CVD mortality in total population were 19.0, 4.7, 13.5, and 6.4 per 1000 person-years, respectively. The multivariate sex-adjusted hazard ratios (HRs) of HTN-/DM+ for CHD, stroke, all-cause mortality and CVD mortality were 1.19 (confidence interval (CI): 0.9-1.57), 1.07 (CI: 0.63-1.82), 1.62 (CI: 1.2-2.18), and 1.28 (CI: 0.83-1.97); the corresponding HRs for HTN+/DM+ were 1.96 (CI: 1.57-2.46), 1.66 (CI: 1.1-2.52), 2.32 (CI: 1.8-2.98), and 2.6 (CI: 1.85-3.65) respectively. The associations between HTN/DM status with stroke incidence and all-cause mortality were stronger among men than in women (P for interaction <0.05). Compared to HTN+/DM-, HTN-/DM+ increases all-cause mortality by 62%, however, they are not considerably different regarding CHD, stroke incidence and CVD mortality.

Aims: To determine the effect of different glucose categories on incident cardiovascular disease (CVD) and all-cause mortality in a population-based cohort., Methods: A total of 834 individuals aged 65 years and older without a history of CVD at baseline were stratified according to 2-h post-load glucose fasting glucose test into six categories including: (i) normal fasting glucose/normal glucose tolerance; (ii) prediabetes, (iii) isolated fasting hyperglycemia (IFH); (iv) isolated post-challenge hyperglycemia (IPH); (v) IPH and IFH; and (vi) known diabetes mellitus. The prognostic significance of these groups on CVD and total mortality were examined by Cox proportional hazard ratios in a multivariate adjusted model., Results: Over 9 years of follow up, 186 incidents of CVD and 218 deaths occurred (72 CVD mortality).Of the population, 45.2%, 30.7%, 1.2%, 6.1% 4.7%, and 11.9% were normal fasting glucose/normal glucose tolerance, prediabetes IFH, IPH, IFH and IPH, and known diabetes mellitus, respectively. Multivariate adjusted hazard ratios for CVD were 1.13 (95% CI 0.78-1.64), 1.03 (95% CI 0.25-4.22), 1.17 (95% CI 0.65-2.11), 2.52 (95% CI 1.43-4.42) and 2.39 (95% CI 1.55-3.69), and for CVD mortality were 0.59 (95% CI 0.27-1.30), 2.02 (95% CI 0.27-15.15), 1.26 (95% CI 0.51-3.16), 3.57 (95% CI 1.64-7.75), and 4.70 (95% CI 2.54-8.69) for prediabetes, IFH, IPH, IFH and IPH, and known diabetes mellitus phenotypes, respectively. Corresponding hazard ratios for all-cause mortality in multivariate model adjusted for prevalent CVD were 1.07 (95% CI 0.73-1.57), 0.59 (95% CI 0.08-4.30), 0.92 (95% CI 0.5-1.70), 2.31 (95% CI 1.33-4.01) and 3.88 (95% CI 2.70-5.55), respectively., Conclusion: Among the elderly population with newly diagnosed diabetes, only the combined IFH and IPH phenotype, but not IFH or IPH alone, was a significant predictor of CVD and mortality events. Prediabetes was not associated with any risk. Geriatr Gerontol Int 2016; 16: 1263-1271., (© 2015 Japan Geriatrics Society.)

Objectives: Identifying an appropriate set of predictors for the outcome of interest is a major challenge in clinical prediction research. The aim of this study was to show the application of some variable selection methods, usually used in data mining, for an epidemiological study. We introduce here a systematic approach., Study Design and Setting: The P-value-based method, usually used in epidemiological studies, and several filter and wrapper methods were implemented to select the predictors of diabetes among 55 variables in 803 prediabetic females, aged ≥ 20 years, followed for 10-12 years. To develop a logistic model, variables were selected from a train data set and evaluated on the test data set. The measures of Akaike information criterion (AIC) and area under the curve (AUC) were used as performance criteria. We also implemented a full model with all 55 variables., Results: We found that the worst and the best models were the full model and models based on the wrappers, respectively. Among filter methods, symmetrical uncertainty gave both the best AUC and AIC., Conclusion: Our experiment showed that the variable selection methods used in data mining could improve the performance of clinical prediction models. An R program was developed to make these methods more feasible and visualize the results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To determine the extent to which burden of cardiovascular disease (CVD) outcomes among diabetic population is attributable to hypertension. Nine-year follow-up data were secured for 7068 participants aged ≥ 20 years old, free from CVD at baseline. Cox proportional hazards regression was implemented to estimate hazard ratios (HRs) of hypertension. Population-attributable hazard fraction (PAHF) was used to assess proportion of diabetic population hazard of CVD events and mortality attributable to hypertension. In the whole population, irrespective of diabetes or hypertension status, incidence rate (95% CI) of CVD, coronary heart disease (CHD), as well as CVD and all-cause mortality per 1000 person-year were 8.3 (7.6-9.0), 7.1 (6.5-7.8), 1.8 (1.5-2.1) and 3.9 (3.5-4.5), respectively. Among diabetes participants, hypertension was a risk factor for CHD (HR = 1.63, 95% CI 1.15-2.03), CVD (HR = 1.74, 95% CI 1.50-2.41), CVD mortality (HR = 1.65, 95% CI 0.87-3.12) and all-cause mortality (HR = 1.53, 95% CI 0.97-2.42). HRs, however, were not statistically significant for all-cause or CVD mortality. PAHFs (%) of hypertension was 27.5 (95% CI 8.3-42.6) for CHD, 29.6 (95% CI 10.6-44.4) for CVD, 27.9 (95% CI - 17.2 to 55.7) for CVD mortality and 22.6 (95% CI - 5.9 to 43.4) for all-cause mortality. Our study shows that there is an excess risk of CVD in hypertensive patients with diabetes related to inadequate control of blood pressure.

We validated the transportability of the updated diabetes prediction model from Atherosclerosis Risk in Communities (ARIC) Study, to a Middle Eastern population. We investigated 3,721 participants of the Tehran Lipid and Glucose Study (TLGS) aged ≥20 years, free of diabetes at baseline. They underwent a standard 75gr 2-h post-challenge plasma glucose test that was repeated every 3 years using the same protocol. All the models were tested with respect to discrimination and calibration. We confirm the findings of Kahn et al. (Ann Intern Med 150(11):741-751, 2009) in a middle-aged, Middle Eastern population. We obtained the same predictive discrimination for the ARIC model (C statistic: men 0.790 and women 0.829) as for the TLGS' own model (men 0.824 and women 0.847) and validated a good calibration for the updated ARIC diabetes prediction model in the TLGS sample. Among men, optimal cut-point was set to the score of 31 where the maximum value of sensitivity (71.6%) plus specificity (75.3%) was achieved. Among women, the optimal point was set to the score of 38 with sensitivity of 67.1% and specificity of 85.0%. The updated ARIC model predicted the individual diabetes risk with a high level of sensitivity and specificity in the TLGS population, which was comparable with that of original sample. More parsimonious model incorporating age, family history of diabetes, waist circumference, pulse rate, and fasting plasma glucose, which were significantly associated with the risk of incident diabetes in the TLGS population, could be equally effective in predicting diabetes.

Background: Data about the risk factors of stroke are sparse in the Middle East populations. We aimed to determine the potential risk factors and their population attributable fraction (PAF) for stroke in an Iranian population., Methods: A cohort Study consisted of 1089 men and 1289 women, with mean (SD) ages of 61.1(7.6) and 59.0(6.7) years, respectively. Cox regression was implemented to estimate the hazard ratio (HR) of each risk factor for stroke events in a stepwise method. We calculated a multivariate adjusted population attributable fraction (PAF) for any risk factors remained in the model., Results: During 9.3 years of follow-up, 69 events of stroke occurred with incidence rates of 4.5 (95% CI: 3.3-6.0) and 2.5 (1.7-3.6) in 1000 person-years for men and women respectively. Among potential risk factors, only age ≥ 65 years (HR: 2.03, CI: 1.24-3.31), male gender (HR: 2.00, CI: 1.16-3.43), hypertension (HR: 3.03, CI: 1.76-5.22), diabetes mellitus (HR: 2.18, CI: 1.34-3.56), and chronic kidney disease (CKD) (HR: 2.01, CI: 1.22-3.33), were independently associated with increased risk of stroke events in the total population. A paired homogeneity test showed that the hazard ratio of CKD did not differ from other independent risk factors. The PAFs were 29.7% and 25% for male gender and age ≥ 65 as non-modifiable and 48.6%, 29.1% and 22.0% for hypertension, CKD and diabetes as modifiable risk factors respectively., Conclusion: Following this population based study of Iranians, we demonstrated that among modifiable risk factors, CKD as well as hypertension and diabetes are the strongest independent predictors of stroke.

The aim of this study is to determine safe fasting plasma glucose (FPG) levels. We included data on 5,960 individuals aged ≥20 years at baseline with at least one follow-up examination. Diabetes was ascertained in accordance with American Diabetes Association criteria, using standard 2-h post-challenge plasma glucose test. Multivariate restricted cubic splines Weibull regression was implemented for interval-censored survival data on incident diabetes. We used Harrell's C statistic for discrimination, Nam-D'Agostino χ(2) for calibration, and Royston's R(2) for variations in the outcome explained by models. During a 6-year median follow-up, 369 incident cases of diabetes were ascertained. Family history of diabetes, systolic blood pressure, waist-to-height ratio, and triglyceride-to-high-density lipoprotein cholesterol ratio, independent of FPG and each other remained associated with incident diabetes. The cubic splines model achieved good calibration (χ(2) = 12.1) and discrimination (C = 0.828) and explained 75% of variation in the time until incident diabetes. A J-shaped FPG-diabetes relationship was observed. Descending arm of the dose-response relationship curve corresponded to increasing FPG levels up to 4.0 mmol l(-1), where it started increasing. The risk of incident diabetes decreased with decreasing levels of FPG down to 4.0 mmol l(-1), where the risk stopped decreasing. Multivariate-adjusted risk of incident diabetes was zero at FPG = 5.05 mmol l(-1). Although currently there is no firm evidence to show that early intervention among individuals with the elevated FPG levels could prevent or delay onset of diabetes, individuals with FPG levels below 5.05 mmol l(-1) could be safely reassured about their near-term risk of developing incident diabetes and screened on a less frequent basis.

Background: We contrasted impacts on all-cause and cardiovascular disease (CVD) mortality of diabetes vs. CVD., Methods: Among participants the Tehran lipid and glucose study aged ≥ 30 years (n = 9752), we selected those who participated in the follow-up study until 20 March 2009 (n = 8795). Complete data on covariate were available for 8, 469 participants, contributing to a 67935 person-year follow up. In the analysis of outcomes (all-cause and CVD mortality), diabetes and CVD were assessed using Cox proportional hazard regression model adjusting for established CVD risk factors. We used population attributable hazard fraction (PAHF) and rate advancement period (RAP) that expresses how much sooner a given mortality rate is reached among exposed than among unexposed individuals., Results: Ten percent of the participants self-reported to have pervious CVD, and diabetes was ascertained in 17% of participants at baseline examination. During a median follow-up of 9 years 386 participants died of which 184 were due to CVD. All-cause and CVD mortality rate (95% CIs) were 5.5 (5.0-6.1) and 2.6 (2.3-3.0) per 1000 person-year, respectively. The PAHF of all-cause mortality for diabetes 9.2 (7.3-11.1) was greater than the one for CVD 3.5 (1.1-5.5). RAP estimates for all-cause mortality associated with diabetes ranged from 7.4 to 8.6 years whereas the RAP estimates for all-cause mortality associated with CVD ranged from 3.1 to 4.3 years. The PAHF of CVD mortality for diabetes 9.4 (6.8-12.0) was greater than the one for CVD 4.5 (1.8-7.0). RAP estimates for CVD mortality associated with diabetes ranged from 8.2 to 9.8 years whereas the RAP estimates for CVD mortality associated with CVD ranged from 4.7 to 6.7 years., Conclusions: We demonstrated that diabetes, which was shown to be keeping pace with prevalent CVD in terms of conferring excess risk of incident CVD, is currently causing more deaths in the population than does CVD.

Elevated blood pressure (BP) may lead to incident diabetes. However, data about the effect of different BP components on incident diabetes in Middle Eastern women is lacking. We evaluated systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) as independent predictors of diabetes in Iranian women. We performed a population-based prospective study among 3028 non-diabetic women, aged ≥20 years. Odds ratios (ORs) of diabetes were calculated for every 1 s.d. increase in SBP, DBP, PP and MAP. During ≈6 years of follow-up, 220 women developed diabetes. There were significant interactions between family history of diabetes and SBP, PP and MAP (P≤0.01) in predicting incident diabetes. In women without a family history of diabetes, all BP components were significantly associated with diabetes in the age-adjusted model; the risk factor-adjusted ORs were significant (P<0.05) for SBP, PP and MAP (1.30, 1.34 and 1.27, respectively) with similar predictive ability (area under the receiver operating characteristic curve ≈83%). In women with family history of diabetes, in the age-adjusted model, SBP, DBP and MAP were associated with diabetes; in multivariable model, they were not independent predictors of diabetes. In conclusion, in women without family history of diabetes, SBP, PP and MAP, were independent predictors of diabetes with almost similar predictive ability; hence, in the evaluation of the risk of BP components for prediction of diabetes, the presence of family history of diabetes should be considered.

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.

Background: Metabolic syndrome (MetS) and body mass index (BMI, kg.m(-2)) are established independent risk factors in the development of diabetes; we prospectively examined their relative contributions and joint relationship with incident diabetes in a Middle Eastern cohort., Method: participants of the ongoing Tehran lipid and glucose study are followed on a triennial basis. Among non-diabetic participants aged≥ 20 years at baseline (8,121) those with at least one follow-up examination (5,250) were included for the current study. Multivariate logistic regression models were used to estimate sex-specific adjusted odd ratios (ORs) and 95% confidence intervals (CIs) of baseline BMI-MetS categories (normal weight without MetS as reference group) for incident diabetes among 2186 men and 3064 women, aged ≥ 20 years, free of diabetes at baseline., Result: During follow up (median 6.5 years); there were 369 incident diabetes (147 in men). In women without MetS, the multivariate adjusted ORs (95% CIs) for overweight (BMI 25-30 kg/m(2)) and obese (BMI≥30) participants were 2.3 (1.2-4.3) and 2.2 (1.0-4.7), respectively. The corresponding ORs for men without MetS were 1.6 (0.9-2.9) and 3.6 (1.5-8.4) respectively. As compared to the normal-weight/without MetS, normal-weight women and men with MetS, had a multivariate-adjusted ORs for incident diabetes of 8.8 (3.7-21.2) and 3.1 (1.3-7.0), respectively. The corresponding ORs for overweight and obese women with MetS reached to 7.7 (4.0-14.9) and 12.6 (6.9-23.2) and for men reached to 3.4(2.0-5.8) and 5.7(3.9-9.9), respectively., Conclusion: This study highlights the importance of screening for MetS in normal weight individuals. Obesity increases diabetes risk in the absence of MetS, underscores the need for more stringent criteria to define healthy metabolic state among obese individuals. Weight reduction measures, thus, should be encouraged in conjunction with achieving metabolic targets not addressed by current definition of MetS, both in every day encounter and public health setting.

Background: Diabetes is a strong risk factor for cardiovascular disease (CVD).The relative role of various lipid measures in determining CVD risk in diabetic patients is still a subject of debate. We aimed to compare performance of different lipid measures as predictors of CVD using discrimination and fitting characteristics in individuals with and without diabetes mellitus from a Middle East Caucasian population., Methods: The study population consisted of 1021 diabetic (men = 413, women = 608) and 5310 non-diabetic (men = 2317, women = 2993) subjects, aged > or = 30 years, free of CVD at baseline. The adjusted hazard ratios (HRs) for CVD were calculated for a 1 standard deviation (SD) change in total cholesterol (TC), log-transformed triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using Cox proportional regression analysis. Incident CVD was ascertained over a median of 8.6 years of follow-up., Results: A total of 189 (men = 91, women = 98) and 263(men = 169, women = 94) CVD events occurred, in diabetic and non-diabetic population, respectively. The risk factor adjusted HRs to predict CVD, except for HDL-C, TG and TG/HDL-C, were significant for all lipid measures in diabetic males and were 1.39, 1.45, 1.36 and 1.16 for TC, LDL-C, non- HDL-C and TC/HDL-C respectively. In diabetic women, using multivariate analysis, only TC/HDL-C had significant risk [adjusted HR1.31(1.10-1.57)].Among non-diabetic men, all lipid measures, except for TG, were independent predictors for CVD however; a 1 SD increase in HDL-C significantly decreased the risk of CVD [adjusted HR 0.83(0.70-0.97)].In non-diabetic women, TC, LDL-C, non-HDL-C and TG were independent predictors.There was no difference in the discriminatory power of different lipid measures to predict incident CVD in the risk factor adjusted models, in either sex of diabetic and non-diabetic population., Conclusion: Our data according to important test performance characteristics provided evidence based support for WHO recommendation that along with other CVD risk factors serum TC vs. LDL-C, non-HDL-C and TC/HDL-C is a reasonable lipid measure to predict incident CVD among diabetic men. Importantly, HDL-C did not have a protective effect for incident CVD among diabetic population; given that the HDL-C had a protective effect only among non- diabetic men.

Background: To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged > or = 20 years., Methods: The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes., Results: The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (> or = 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57-1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1-2.4)., Conclusion: In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI > or = 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.

Aims: To compare the ability of definitions of Metabolic Syndrome (MetS) in the prediction of type 2 diabetes., Methods: We examined 4756 subjects in an Iranian population who were non-diabetic at baseline. After 3.6 years, 188 individuals developed diabetes., Results: Impaired glucose tolerance (IGT) and MetS definitions predicted type 2 diabetes with odds ratios ranging from 3.7 to 11.9 (all P<0.05) although IGT had the highest area under the receiver operator characteristic (aROC) curve than all the MetS definitions. Reduction of glucose in the National Cholesterol Education Program (NCEP) definition of the MetS increased diabetes prediction, but adding the family history of diabetes did not change aROC curves. The International Diabetes Federation (IDF) definition had the highest sensitivity and false positive rate (72.2 and 35.1%, respectively) and the WHO definition had the lowest ones (54.8 and 9.2%, respectively) for predicting diabetes. The positive predictive values of all definitions were low (8.6-19.7%) but their negative predictive values were around 98%., Conclusions: In Iranian population, the MetS was inferior to IGT for predicting type 2 diabetes. The NCEP definition of the MetS with reduced level of glucose (not including the family history of diabetes) and IDF definition predicted type 2 diabetes at least as well as WHO definition.

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Diabetes and dysglycemia have a high prevalence in Iranian population but the information about their impact on the cardiovascular disease (CVD) risk is scarce in this population. This study aimed to determine the risk of CVD according to glucose tolerance status."n"nMethods: We ascertained cases with incident CVD in a population of 1752 men and 2273 women, 40 years old and over and free of CVD at the beginning of study, during a follow up with a median of 7.6 years. To calculate hazard ratio (HR) for CVD, we controlled traditional risk factors, including age, body mass index, waist, total cholesterol, HDL-cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, education, smoking, hypertension medication, lipid lowering medication and family history of premature CVD and diabetes."n"nResults: Cardiovascular events occurred in 197 men and 143 women. Its incidence density was 11.8 per 1000 person-years (95% confidence interval: 10.6 to 13.1) totally. Multiple adjusted HR in women with known diabetes was 3.88 (95%CI: 2.40 to 6.27) and with newly diagnosed was 2.34 (95%CI: 1.39 to 3.95) and the corresponding values for men were 1.72 (95%CI: 1.00- 2.95) and 1.52 (95%CI: 1.01- 2.31) respectively. Impaired fasting glucose and impaired glucose tolerance increased 56% the risk of CVD in women (HR: 1.56 with 95% CI, 1.00 to 2.45), just in the age adjusted model."n"nConclusion: All diabetic patients should receive primary prevention for CVD intensively, regardless of whether they are newly diagnosed or are known cases; specially, females who have abnormal glucose metabolism.