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Erfan Sadeghi,1,2 Sayed Mohsen Hosseini,1 Mehrdad Vossoughi,3 Ashraf Aminorroaya,4 Massoud Amini4 1Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran; 2Student Research Committee, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran; 3Oral and Dental Disease Research Center, Department of Dental Public Health, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran; 4Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, IranCorrespondence: Sayed Mohsen HosseiniDepartment of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan 81746-73461, IranTel +98 313 792 3251Fax +98 311 668 2509Email hosseini@hlth.mui.ac.irPurpose: Dyslipidemia is claimed to be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, first-degree relatives (FDRs) of patients with T2DM are reported to be at higher risk. The aim of this study was to evaluate the association between serum lipid profile and T2DM incidence in FDRs.Patients and methods: Information on 1222 T2DM FDRs during 14 years of follow-up was retrieved. All individuals were examined for diabetes status and dyslipidemia once a year. We used a Bayesian joint longitudinal-survival model to assess the association.Results: Our data showed that a 10 mg/dL increase in triglycerides (TG), very-low-density lipoprotein (VLDL), and non-high-density lipoprotein (non-HDL) cholesterol levels during the follow-up period was associated with an increased risk of diabetes by 5%, 29%, and 6.6%, respectively. Moreover, for every one-unit increase in the TG to HDL ratio, the T2DM incidence increased by 35%. Subgroup analysis also showed that the increased risk of diabetes was significant only in female FDRs, so that a 10 mg/dL increase in TG and VLDL cholesterol level and a one-unit increase in TG to HDL ratio in female FDRs resulted in an increased risk of diabetes by 7.8%, 46%, and 64%, respectively. However, analysis of HDL, low-density lipoprotein (LDL), total cholesterol (TC), TC to HDL, and LDL to HDL cholesterol levels/ratios did not find any statistically significant associations.Conclusion: Increases in TG, VLDL, non-HDL cholesterol level, and TG to HDL ratio are associated with an increased risk of T2DM in FDRs, especially in female FDRs.Keywords: diabetes mellitus, joint model, longitudinal studies, survival

Roqayeh Aliyari,1 Ebrahim Hajizadeh,1 Ashraf Aminorroaya,2 Farshad Sharifi,3 Iraj Kazemi,4 Ahmad-Reza Baghestani5 1Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 2Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; 3Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Statistics, Faculty of Sciences, University of Isfahan, Isfahan, Iran; 5Department of Biostatistics, Physiotherapy Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Ebrahim HajizadehDepartment of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 1411713116, IranTel +982182883810Fax +982182884510Email hajizadeh@modares.ac.irAshraf AminorroayaIsfahan Endocrine and Metabolism Research, Isfahan University of Medical Sciences, Isfahan, IranTel +98 313 335 9933Fax +98 313 337 3733Email aminorroaya@med.mui.ac.irBackground: Increase in the prevalence of type 2 diabetic mellitus (T2DM) as a complex disease, its complications, and spread has become a dominant global health threat in recent decades.Objective: The aim of the current study was to investigate the impact of risk factors and transition probability on the development and progression of the late complications of T2DM.Methods: This study was an open cohort one which was conducted at Isfahan Endocrine and Metabolism Research Center (IEMRC). The data were collected from 1993 to 2018. The sample size consisted of 2519 adults diagnosed with type 2 diabetes. We applied the homogeneous multistate models including no complication, retinopathy alone, coronary artery disease (CAD), microalbuminuria, retinopathy and CAD, and the final absorbing mortality states.Results: Based on our results, time-varying hypertension strongly intensified the hazard of transition to mortality in CAD, no complication, CAD and retinopathy, and retinopathy patients by 4.99, 4.09, 3.42, and 2.65 times, respectively. Hypertension seemed to be a potential factor for the transition of microalbuminuria to no complication in diabetic patients. One-unit increase in LDL increased the hazard ratio of transition from CAD, and retinopathy and CAD to mortality by 1.8% and 2.4%, respectively. Moreover, one level increase in time-varying HbA1c increased the hazard ratio of transition to retinopathy and mortality among no complication diabetic patients by 30% and 67%, respectively. One level increase in time-varying HbA1c also intensified the hazard ratio of transition from retinopathy to mortality by 45%. The same level of increase in time-varying HbA1c also intensified the hazard ratio of transition from CAD alone to CAD and retinopathy, and microalbuminuria to retinopathy by 26% and 50%, respectively.Conclusion: In addition to glycemic control, our study indicates that controlling hypertension and hyperlipidemia is more effective in reducing mortality and the diabetic macro- and microvascular complications.Keywords: T2DM, hypertension, CAD, microalbuminuria, retinopathy, diabetics complications, multistate models, transition probability

Moluk Hadi Alijanvand,1–3 Ashraf Aminorroaya,2 Iraj Kazemi,4 Sima Aminorroaya Yamini,5 Mohsen Janghorbani,1,2 Masoud Amini,2 Marjan Mansourian1,21Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran; 2Isfahan Endocrine and Metabolism Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran; 3Student Research Center, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran; 4Department of Statistics, College of Science, University of Isfahan, Isfahan, Iran; 5Department of Engineering and Mathematics, Sheffiled Hallam University, Sheffield, UKBackground: Moderately increased albuminuria (MIA) is strongly associated with hypertension (HTN) in patients with type 2 diabetic mellitus (T2DM). However, the association between risk factors and coexisting HTN and MIA remains unassessed.Objectives: This study aimed to determine both cross-sectional and longitudinal associations of risk factors with HTN and MIA comorbidity in patients with T2DM.Methods: A total of 1,600 patients with T2DM were examined at baseline and longitudinal data were obtained from 1,337 T2DM patients with at least 2 follow-up visits to assess the presence of HTN alone (yes/no), MIA alone (yes/no) and the coexistence of both (yes/no) in a 9-year open cohort study between 2004 and 2013. Bivariate mixed-effects logistic regression with a Bayesian approach was employed to evaluate associations of risk factors with HTN and MIA‎ comorbidity in the longitudinal assessment.Results: After adjustment for age and BMI, patients with uncontrolled plasma glucose, as a combined index of the glucose profile, were more likely to have HTN [odds ratio (OR): 1.73 with 95% Bayesian credible intervals (BCI) 1.29–2.20] and MIA [OR: 1.34 (‎95% BCI 1.13–1.62)]. The risks of having HTN and MIA were increased by a one-year raise in diabetes duration [with 0.89 (95% BCI 0.84–0.96) and 0.81 (95% BCI 0.73–0.92) ORs, respectively] and a one-unit increase in non-high-density lipoprotein-cholesterol (Non-HDL-C) [with 1.30 (95% BCI 1.23–1.34) and 1.24 (95% BCI 1.14–1.33) ORs, respectively].Conclusions: T2DM patients with HTN,‎ MIA, and the coexistence of both had uncontrolled plasma glucose, significantly higher Non-HDL-C, and shorter diabetes duration than the other T2DM patients. Duration of diabetes and uncontrolled plasma glucose index showed the stronger effects on HTN and MIA comorbidity than on each condition separately.Keywords: hypertension, moderately increased albuminuria, microalbuminuria, type 2 diabetes, comorbidity, risk factor

Selected glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have cardioprotective effects in patients with type 2 diabetes mellitus (T2D) and elevated cardiovascular risk. Prescription and consistent use of these medications are essential to realizing their benefits. In a nationwide deidentified United States administrative claims database of adults with T2D, the prescription practices of GLP-1RAs and SGLT-2i were evaluated across guideline-directed co-morbidity indications from 2018 to 2020. The monthly fill rates were assessed for 12 months after the initiation of therapy by calculating the proportion of days with consistent medication use. Of 587,657 subjects with T2D, 80,196 (13.6%) were prescribed GLP-1RAs and 68,149 (11.5%) SGLT-2i from 2018 to 2020, representing 12.9% and 11.6% of patients with indications for each medication, respectively. In new initiators, 1-year fill rate was 52.5% for GLP-1RAs and 52.9% for SGLT-2i, which was higher for patients with commercial insurance than those with Medicare Advantage plans for both GLP-1RAs (59.3% vs 51.0%, p

Abstract Artificial intelligence (AI) can detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs). Wearable devices could allow for broad AI-based screening but frequently obtain noisy ECGs. We report a novel strategy that automates the detection of hidden cardiovascular diseases, such as LVSD, adapted for noisy single-lead ECGs obtained on wearable and portable devices. We use 385,601 ECGs for development of a standard and noise-adapted model. For the noise-adapted model, ECGs are augmented during training with random gaussian noise within four distinct frequency ranges, each emulating real-world noise sources. Both models perform comparably on standard ECGs with an AUROC of 0.90. The noise-adapted model performs significantly better on the same test set augmented with four distinct real-world noise recordings at multiple signal-to-noise ratios (SNRs), including noise isolated from a portable device ECG. The standard and noise-adapted models have an AUROC of 0.72 and 0.87, respectively, when evaluated on ECGs augmented with portable ECG device noise at an SNR of 0.5. This approach represents a novel strategy for the development of wearable-adapted tools from clinical ECG repositories.

Background The North Africa and Middle East (NAME) region has one of the highest burdens of ischemic heart disease (IHD) worldwide. This study reports the contemporary epidemiology of IHD in NAME. Methods and Results We estimated the incidence, prevalence, deaths, years of life lost, years lived with disability, disability‐adjusted life years (DALYs), and premature mortality of IHD, and its attributable risk factors in NAME from 1990 to 2019 using the results of the GBD (Global Burden of Disease study 2019). In 2019, 0.8 million lives and 18.0 million DALYs were lost due to IHD in NAME. From 1990 to 2019, the age‐standardized DALY rate of IHD significantly decreased by 33.3%, mostly due to the reduction of years of life lost rather than years lived with disability. In 2019, the proportion of premature death attributable to IHD was higher in NAME compared with global measures: 26.8% versus 16.9% for women and 18.4% versus 14.8% for men, respectively. The age‐standardized DALY rate of IHD attributed to metabolic risks, behavioral risks, and environmental/occupational risks significantly decreased by 28.7%, 37.8%, and 36.4%, respectively. Dietary risk factors, high systolic blood pressure, and high low‐density lipoprotein cholesterol were the top 3 risks contributing to the IHD burden in most countries of NAME in 2019. Conclusions In 2019, IHD was the leading cause of death and lost DALYs in NAME, where premature death due to IHD was greater than the global average. Despite the great reduction in the age‐standardized DALYs of IHD in NAME from 1990 to 2019, this region still had the second‐highest burden of IHD in 2019 globally.

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.