Metabolomics Signature in Prediabetes and Diabetes: Insights From Tandem Mass Spectrometry Analysis.

OBJECTIVE: This study investigates the metabolic differences between normal, prediabetic and diabetic patients with good and poor glycaemic control (GGC and PGC). DESIGN: In this study, 1102 individuals were included, and 50 metabolites were analysed using tandem mass spectrometry. The diabetes diagnosis and treatment standards of the American Diabetes Association (ADA) were used to classify patients. METHODS: The nearest neighbour method was used to match controls and cases in each group on the basis of age, sex and BMI. Factor analysis was used to reduce the number of variables and find influential underlying factors. Finally, Pearson's correlation coefficient was used to check the correlation between both glucose and HbAc1 as independent factors with binary classes. RESULTS: Amino acids such as glycine, serine and proline, and acylcarnitines (AcylCs) such as C16 and C18 showed significant differences between the prediabetes and normal groups. Additionally, several metabolites, including C0, C5, C8 and C16, showed significant differences between the diabetes and normal groups. Moreover, the study found that several metabolites significantly differed between the GGC and PGC diabetes groups, such as C2, C6, C10, C16 and C18. The correlation analysis revealed that glucose and HbA1c levels significantly correlated with several metabolites, including glycine, serine and C16, in both the prediabetes and diabetes groups. Additionally, the correlation analysis showed that HbA1c significantly correlated with several metabolites, such as C2, C5 and C18, in the controlled and uncontrolled diabetes groups. CONCLUSIONS: These findings could help identify new biomarkers or underlying markers for the early detection and management of diabetes.

Protocol for preliminary, multicenteric validation of "PoCOsteo device": A point of care tool for proteomic and genomic study of osteoporosis.

One of the goals of the HORIZON 2020 project PoCOsteo was to develop a medical device, which would measure and/or quantify proteomic as well as genomic factors as present in whole blood samples collected through finger prick. After validating the tool in the clinical setting, the next step would be its clinical validation based on the existing guidelines. This article presents the protocol of a validation study to be carried out independently at two different centers (Division of Endocrinology and Diabetology at the Medical University of Graz as a clinic-based cohort, and the Endocrinology and Metabolism Research Institute at the Tehran University of Medical Sciences as a population-based cohort). It aims to assess the tool according to the Clinical & Laboratory Standards Institute guidelines, confirming if the proteomics and genomics measurements provided by the tool are accurate and reproducible compared with the existing state-of-the-art tests. This is the first time that such a detailed protocol for lab validation of a medical tool for proteomics and genomic measurement is designed based on the existing guidelines and thus could be used as a template for clinical validation of future point-of-care tools. Moreover, the multicentric cohort design will allow the study of a large number of diverse individuals, which will improve the validity and generalizability of the results for different settings.

Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: a candidate-gene association study in breast cancer patients.

PURPOSE: The current candidate gene association study aims to investigate tag SNPs from the TACR1 gene as pharmacogenetic predictors of response to the antiemetic guidelines-recommended, NK-1 receptor antagonist-based, triple antiemetic regimens. METHODS: A set of eighteen tag SNPs of TACR1 were genotyped in breast cancer patients receiving anthracycline and cyclophosphamide (with/without docetaxel) applying real-time PCR-HRMA. Data analysis for 121 ultimately enrolled patients was initiated by defining haplotype blocks using PHASE v.2.1. The association of each tag SNP and haplotype alleles with failure to achieve the defined antiemetic regimen efficacy endpoints was tested using PLINK (v.1.9 and v.1.07, respectively) based on the logistic regression, adjusting for the previously known chemotherapy-induced nausea and vomiting (CINV) prognostic factors. All reported p-values were corrected using the permutation test (n = 100,000). RESULTS: Four variants of rs881, rs17010730, rs727156, and rs3755462, as well as haplotypes containing the mentioned variants, were significantly associated with failure to achieve at least one of the defined efficacy endpoints. Variant annotation via in-silico studies revealed that the non-seed sequence variant, rs881, is located in the miRNA (hsa-miR-613) binding site. The other three variants or a variant in complete linkage disequilibrium with them overlap a region of high H3K9ac-promoter-like signature or regions of high enhancer-like signature in the brain or gastrointestinal tissue. CONCLUSION: Playing an essential role in regulating TACR1 expression, gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the NK-1 receptor antagonist-based, triple antiemetic regimens. If clinically approved, modifying the NK-1 receptor antagonist dose leads to better management of CINV in risk-allele carriers.

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia.

Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1-3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.

Insight into the Predictive Power of Surrogate Diagnostic Indices for Identifying Individuals with Metabolic Syndrome.

BACKGROUND: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations. METHODS: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences. RESULTS: The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals. CONCLUSION: The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). OBJECTIVE AND RATIONALE: This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. METHODS: A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. RESULTS: A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. CONCLUSION: The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

Metabolomics signature of cardiovascular disease in patients with diabetes, a narrative review.

Objectives: The exact underlying mechanism of developing diabetes-related cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is not clear. Metabolomics can provide a platform enabling the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The aim of this review is to summarize the available evidence on the relationship between metabolomics and cardiovascular diseases in patients with diabetes. Methods: The literature was searched to find out studies that have investigated the relationship between the alteration of specific metabolites and cardiovascular diseases in patients with diabetes. Results: Evidence proposed that changes in the metabolism of certain amino acids, lipids, and carbohydrates, independent of traditional CVD risk factors, are associated with increased CVD risk. Conclusions: Metabolomics can provide a platform to enable the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The association of the alteration in specific metabolites with CVD may be considered in the investigations for the development of new therapeutic targets for the prevention of CVD in patients with diabetes mellitus.

Evaluation of the diabetes care cascade and compliance with WHO global coverage targets in Iran based on STEPS survey 2021.

This study aimed to investigate the diabetes mellitus (DM) and prediabetes epidemiology, care cascade, and compliance with global coverage targets. We recruited the results of the nationally representative Iran STEPS Survey 2021. Diabetes and prediabetes were two main outcomes. Diabetes awareness, treatment coverage, and glycemic control were calculated for all population with diabetes to investigate the care cascade. Four global coverage targets for diabetes developed by the World Health Organization were adopted to assess the DM diagnosis and control status. Among 18,119 participants, the national prevalence of DM and prediabetes were 14.2% (95% confidence interval 13.4-14.9) and 24.8% (23.9-25.7), respectively. The prevalence of DM treatment coverage was 65.0% (62.4-67.7), while the prevalence of good (HbA1C < 7%) glycemic control was 28.0% (25.0-31.0) among all individuals with diabetes. DM diagnosis and statin use statics were close to global targets (73.3% vs 80%, and 50.1% vs 60%); however, good glycemic control and strict blood pressure control statistics, were much way behind the goals (36.7% vs 80%, and 28.5% vs 80%). A major proportion of the Iranian population are affected by DM and prediabetes, and glycemic control is poorly achieved, indicating a sub-optimal care for diabetes and comorbidities like hypertension.

Management goal achievements of diabetes care in Iran: study profile and main findings of DiaCare survey.

Aim: This paper presented the methodology and main findings of a population-based survey to determine diabetes care status among type 2 diabetic subjects in Iran. The current study assessed treatment goal achievements in type 2 diabetics, diabetes care service utilization, prevalence of diabetes complications, and psychological effects of diabetes in a representative sample of Iranian population in urban and rural areas. Materials and Methods: This nationwide study was conducted between 2018 and 2020 as the observational survey entitled "Diabetes Care (DiaCare)". We studied a representative sample of participants with type 2 diabetes, aged 35-75 years, living in urban and rural areas in all thirty- one provinces of Iran. Data were collected by an interviewer in a form of a questionnaire that includes demographic and socioeconomic status, family and drug history, lifestyle, and self-reported psychological status according to a Patient's Health Questionnaire (PHQ). Management goal achievements, diabetes care service utilization, diabetes complications and psychological effects of diabetes were also assessed. Physical measurements were measured based on standard protocol. Fasting blood glucose (FBG), HbA1c, lipid profile, and also urine albumin to creatinine ratio were obtained from all participants of the study. Results: Overall, 13,334 people with type 2 diabetes in 31 provinces of Iran completed the survey (response rate: 99.6%). In total 13,321 participants, 6683(50.17%) women and 6638(49.83%) men were included in our analysis. Thirteen recruited patients refused after the consenting process and did not respond. The mean age (SD) of total participants was 54.86 ± 9.44 years and 71.50% were from the urban areas. 13.66% of diabetic patients had achieved the triple target of management [controlled HbA1c, blood pressure, and Low-Density Lipoprotein-Cholesterol (LDL-C)] in the whole country. While 28.74% of people had controlled HbA1c and 33.40% of them had controlled FBG. Diabetic subjects living in rural areas had less controlled HbA1c (23.93 vs. 29.48), controlled FBG (29.50 vs. 34.20) and controlled triple targets (10.45 vs. 14.32) than those living in urban areas. Diabetic neuropathy and diabetic foot were more common in women than men, while end-stage of renal disease (ESRD) was more common in men than women. Conclusions: This population-based study provided representative information about diabetes care in Iran. The high prevalence of diabetes and low proportion of diabetes control in Iran implies that it is necessary to identify factors associated with poor treatment goal achievements. Besides, general improvements in management and care of diabetes are mandatory.

Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score.

Background: The intermediate metabolites associated with the development of atherosclerotic cardiovascular disease (ASCVD) remain largely unknown. Thus, we conducted a large panel of metabolomics profiling to identify the new candidate metabolites that were associated with 10-year ASCVD risk. Methods: Thirty acylcarnitines and twenty amino acids were measured in the fasting plasma of 1,102 randomly selected individuals using a targeted FIA-MS/MS approach. The 10-year ASCVD risk score was calculated based on 2013 ACC/AHA guidelines. Accordingly, the subjects were stratified into four groups: low-risk (n = 620), borderline-risk (n = 110), intermediate-risk (n = 225), and high-risk (n = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis. Results: C4DC, C8:1, C16OH, citrulline, histidine, alanine, threonine, glycine, glutamine, tryptophan, phenylalanine, glutamic acid, arginine, and aspartic acid were significantly associated with the 10-year ASCVD risk score (p-values ≤ 0.044). The high-risk group had higher odds of factor 1 (12 long-chain acylcarnitines, OR = 1.103), factor 2 (5 medium-chain acylcarnitines, OR = 1.063), factor 3 (methionine, leucine, valine, tryptophan, tyrosine, phenylalanine, OR = 1.074), factor 5 (6 short-chain acylcarnitines, OR = 1.205), factor 6 (5 short-chain acylcarnitines, OR = 1.229), factor 7 (alanine, proline, OR = 1.343), factor 8 (C18:2OH, glutamic acid, aspartic acid, OR = 1.188), and factor 10 (ornithine, citrulline, OR = 1.570) compared to the low-risk ones; the odds of factor 9 (glycine, serine, threonine, OR = 0.741), however, were lower in the high-risk group. "D-glutamine and D-glutamate metabolism", "phenylalanine, tyrosine, and tryptophan biosynthesis", and "valine, leucine, and isoleucine biosynthesis" were metabolic pathways having the highest association with borderline/intermediate/high ASCVD events, respectively. Conclusions: Abundant metabolites were found to be associated with ASCVD events in this study. Utilization of this metabolic panel could be a promising strategy for early detection and prevention of ASCVD events.

The association between acylcarnitine and amino acids profile and metabolic syndrome and its components in Iranian adults: Data from STEPs 2016.

Background: Evidence, albeit with conflicting results, has suggested that cardiometabolic risk factors, including obesity, type 2 diabetes (T2D), dyslipidemia, and hypertension, are highly associated with changes in metabolic signature, especially plasma amino acids and acylcarnitines levels. Here, we aimed to evaluate the association of circulating levels of amino acids and acylcarnitines with metabolic syndrome (MetS) and its components in Iranian adults. Methods: This cross-sectional study was performed on 1192 participants from the large-scale cross-sectional study of Surveillance of Risk Factors of non-communicable diseases (NCDs) in Iran (STEP 2016). The circulating levels of amino acids and acylcarnitines were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in individuals with MetS (n=529) and without MetS (n=663). Results: The higher plasma levels of branched-chain amino acids (Val, Leu), aromatic amino acids (Phe, Tyr), Pro, Ala, Glu, and the ratio of Asp to Asn were significantly associated with MetS, whereas lower circulating levels of Gly, Ser, His, Asn, and citrulline were significantly associated with MetS. As for plasma levels of free carnitine and acylcarnitines, higher levels of short-chain acylcarnitines (C2, C3, C4DC), free carnitine (C0), and long-chain acylcarnitines (C16, C18OH) were significantly associated with MetS. Principal component analysis (PCA) showed that factor 3 (Tyr, Leu, Val, Met, Trp, Phe, Thr) [OR:1.165, 95% CI: 1.121-1.210, P<0.001], factor 7 (C0, C3, C4) [OR:1.257, 95% CI: 1.150-1.374, P<0.001], factor 8 (Gly, Ser) [OR:0.718, 95% CI: 0.651-0.793, P< 0.001], factor 9 (Ala, Pro, C4DC) [OR:1.883, 95% CI: 1.669-2.124, P<0.001], factor 10 (Glu, Asp, C18:2OH) [OR:1.132, 95% CI: 1.032-1.242, P= 0.009], factor 11 (citrulline, ornithine) [OR:0.862, 95% CI: 0.778-0.955, P= 0.004] and 13 (C18OH, C18:1 OH) [OR: 1.242, 95% CI: 1.042-1.480, P= 0.016] were independently correlated with metabolic syndrome. Conclusion: Change in amino acid, and acylcarnitines profiles were seen in patients with MetS. Moreover, the alteration in the circulating levels of amino acids and acylcarnitines is along with an increase in MetS component number. It also seems that amino acid and acylcarnitines profiles can provide valuable information on evaluating and monitoring MetS risk. However, further studies are needed to establish this concept.

Association of plasma acylcarnitines and amino acids with hypertension: A nationwide metabolomics study.

BACKGROUND: Identification of metabolomics profile in subjects with different blood pressure, including normal blood pressure, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension, would be a promising strategy to understand the pathogenesis of hypertension. Thus, we conducted this study to investigate the association of plasma acylcarnitines and amino acids with hypertension in a large Iranian population. METHODS: 1200 randomly selected subjects from the national survey on the Surveillance of Risk Factors of Non-Communicable Diseases in Iran (STEPs 2016) were divided into four groups based on the ACC/AHA hypertension criteria: normal blood pressure (n = 293), elevated blood pressure (n = 135), stage 1 hypertension (n = 325), and stage 2 hypertension (n = 447). Plasma concentrations of 30 acylcarnitines and 20 amino acids were measured using a targeted approach with flow-injection tandem mass spectrometry. Univariate and multivariate logistic regression analysis was applied to estimate the association between metabolites level and the risk of hypertension. Age, sex, BMI, total cholesterol, triglyceride, HDL cholesterol, fasting plasma glucose, use of oral glucose-lowering drugs, statins, and antihypertensive drugs were adjusted in regression analysis. RESULTS: Of 50 metabolites, 34 were associated with an increased likelihood of stage 2 hypertension and 5 with a decreased likelihood of stage 2 hypertension. After full adjustment for potential confounders, 5 metabolites were still significant risk markers for stage 2 hypertension including C0 (OR = 0.75; 95%CI: 0.63, 0.90), C12 (OR = 1.18; 95%CI: 1.00, 1.40), C14:1 (OR = 1.20; 95%CI: 1.01, 1.42), C14:2 (OR = 1.19; 95%CI: 1.01, 1.41), and glycine (OR = 0.81; 95%CI: 0.68, 0.96). An index that included glycine and serine also showed significant predictive value for stage 2 hypertension after full adjustment (OR = 0.86; 95%CI: 0.75, 0.98). CONCLUSIONS: Five metabolites were identified as potentially valuable predictors of stage 2 hypertension.

The Association of Coronary Artery Calcium Score and Osteoporosis in Postmenopausal Women: A Cross-Sectional Study.

BACKGROUND: The association between osteoporosis, a common metabolic bone disorder, and atherosclerosis has been reported in different studies. In this study, we aimed to investigate the association between the coronary artery calcium score (CACS) and bone mineral density (BMD) at different sites and bone biomarkers in postmenopausal women. METHODS: A total of 184 participants were enrolled in this study. The CACS and BMD at different sites, including the spinal, total hip, and femoral neck, were measured using computed tomography angiography and dual energy X-ray absorptiometry, respectively. Serum levels of osteocalcin, ß-C-terminal telopeptide (ß-CTX), parathyroid hormone, and 25-hydroxy-vitamin D were measured. RESULTS: A negative association between CACS and bone biomarker levels (osteocalcin, P=0.021; ß-CTX, P=0.013) was noted. The univariable model showed an association between CACS and osteoporosis of the femoral neck (P=0.03). It was found that with an increase of 10 U in CACS, the odds of osteoporosis at the femoral neck escalates by 2% (odds ratio=1.02, 95% confidence interval, 1.002-1.03) using the multivariate logistic regression model, while such an association with osteoporosis could not be found at the spinal site. The best cutoff point of the calcium score was estimated to be 127. CONCLUSIONS: The results suggest that in postmenopausal women, coronary atherosclerosis is independently associated with osteoporosis of the femoral neck, but such an association could not be detected with spinal osteoporosis. The importance of screening for osteoporosis in patients with cardiovascular disease and the implications of preventive measures in the primary care setting were highlighted considering the common risk factors.

Extracellular vesicles biogenesis, isolation, manipulation and genetic engineering for potential in vitro and in vivo therapeutics: An overview.

The main goals of medicine consist of early detection and effective treatment of different diseases. In this regard, the rise of exosomes as carriers of natural biomarkers has recently attracted a lot of attention and managed to shed more light on the future of early disease diagnosis methods. Here, exosome biogenesis, its role as a biomarker in metabolic disorders, and recent advances in state-of-art technologies for exosome detection and isolation will be reviewed along with future research directions and challenges regarding the manipulation and genetic engineering of exosomes for potential in vitro and in vivo disease diagnosis approaches.

Mapping evidence of Iran diabetes research: protocol for a scoping review.

Background: A considerable amount of research funding goes to diabetes management strategies to improve therapeutic goals and reduce the burden of diabetes. A vast amount of the budget is wasted due to unnecessary studies. A scoping review is a pivotal study to overview the available evidence and avoid research waste. In this review, we will try to find out the scope of available studies on diabetes management interventions, identify associated research gaps, and prioritize future studies. Method: We will carry out a study using Arksey and O'Malley's scoping review framework. We will search the Scopus and PubMed databases from 01/01/2015 till 01/01/2020. Only original articles related to pharmacological and non-pharmacological management interventions will be included. These interventional studies should be conducted on the Iranian population. After data extraction, a descriptive data analysis will be used to present information in different charts or tables. We will evaluate related published articles based on their document type, level of evidence, type of diabetes, subject area, interventions types, main findings and outcomes. Discussion: This study represents the first attempt to sum up available studies related to diabetes management interventions performed in Iran. The results of this study will be useful for all the stakeholders and policy-makers involved in diabetes research. It can help clinicians to be informed about studies on management interventions and can guide scientists eager to diabetes research to choose their future research plans based on diabetes research requirements and gaps.

The role of inflammatory miRNA-mRNA interactions in PBMCs of colorectal cancer and obesity patients.

INTRODUCTION: Inflammation is a critical hallmark in obesity and colorectal cancer (CRC). This study aimed to investigate effective microRNA (miRNA)-messenger RNA (mRNA) interactions on inflammatory networks involved in obesity and CRC. METHODS: The literature searches were applied to identify genes expression reported on peripheral blood mononuclear cells (PBMCs) and/or blood of CRC subjects and to find inflammatory miRNA  in blood samples. Furthermore, bioinformatics analysis was utilized to find inflammatory miRNA:mRNA interactions of the genes. Finally, a case-control study was set to investigate the expression of LAMC1 and GNB3 genes besides miR-10b, miR-506-3p, miR-150-5p, and miR-124-3p in CRC and control subjects. RESULTS: The expression of LAMC1 gene in healthy control groups was associated with body mass index (BMI) (p < .05). The level of miR-10b (p < .001), miR-506 (p < .001), and miR-124 (p <. 001) were significantly increased in PBMCs of CRC patients, while they were not associated with BMI. The level of miR-150 was associated with BMI in healthy subjects (p < .05). CONCLUSIONS: The changes in the level of miR-506 and miR-124 in CRC patients may be associated with the regulatory role of these miRNAs on LAMC1 expression. The LAMC1 may be related to BMI, however, more observational studies on other populations are needed.

Iranian Multi-center Osteoporosis Study (IMOS), 2021-2022: the study protocol.

BACKGROUND: This paper presents the protocol of the 4th round of Iranian Multi-center Osteoporosis Study (IMOS), a national survey with the primary objective of estimating the prevalence of osteoporosis and sarcopenia and their risk factors in a representative sample of urban and rural populations. METHODS: The target population of the survey is all individuals ≥ 50 years in Iran. A multi-stage random sampling method has been used in the study. We stratified the 31 provinces of the country into 5 strata based on the distribution of their potential risk factors for osteoporosis and randomly selected one or two provinces from each stratum. Then, we invited 2530 people aged ≥ 50 years recruited in the 8th National Survey of None Communicable Diseases (NCD) Risk Factors (STEPs-2021) in the selected provinces to participate in IMOS. Body composition measurements including bone mineral density, muscle mass, and fat mass are measured through Dual-energy X-ray Absorptiometry (DXA) method using HOLOGIC (Discovery and Horizon) devices; and Trabecular Bone Score (TBS) is measured on the DXA scans using iNsight software. Anthropometric measurement and physical examinations are made by a trained nurses and other required information are collected through face-to-face interviews made by trained nurses. Laboratory measurements are made in a central lab. The prevalence of osteoporosis and sarcopenia will be estimated after applying sampling design, non-response, and post-stratification weights to the data. DISCUSSION: IMOS will provide valuable information on the prevalence and determinants of osteoporosis and sarcopenia at the national level, and the results can be used in evaluating health system interventions and policymaking in the field of musculoskeletal diseases.

Metabolic signatures of insulin resistance in non-diabetic individuals.

BACKGROUND: Insulin resistance (IR) evolved from excessive energy intake and poor energy expenditure, affecting the patient's quality of life. Amino acid and acylcarnitine metabolomic profiles have identified consistent patterns associated with metabolic disease and insulin sensitivity. Here, we have measured a wide array of metabolites (30 acylcarnitines and 20 amino acids) with the MS/MS and investigated the association of metabolic profile with insulin resistance. METHODS: The study population (n = 403) was randomly chosen from non-diabetic participants of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS 2016). STEPS 2016 is a population-based cross-sectional study conducted periodically on adults aged 18-75 years in 30 provinces of Iran. Participants were divided into two groups according to the optimal cut-off point determined by the Youden index of HOMA-IR for the diagnosis of metabolic syndrome. Associations were investigated using regression models adjusted for age, sex, and body mass index (BMI). RESULTS: People with high IR were significantly younger, and had higher education level, BMI, waist circumference, FPG, HbA1c, ALT, triglyceride, cholesterol, non-HDL cholesterol, uric acid, and a lower HDL-C level. We observed a strong positive association of serum BCAA (valine and leucine), AAA (tyrosine, tryptophan, and phenylalanine), alanine, and C0 (free carnitine) with IR (HOMA-IR); while C18:1 (oleoyl L-carnitine) was inversely correlated with IR. CONCLUSIONS: In the present study, we identified specific metabolites linked to HOMA-IR that improved IR prediction. In summary, our study adds more evidence that a particular metabolomic profile perturbation is associated with metabolic disease and reemphasizes the significance of understanding the biochemistry and physiology which lead to these associations.

Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program.

INTRODUCTION AND OBJECTIVES: Amino acids are the most frequently reported metabolites associated with low bone mineral density (BMD) in metabolomics studies. We aimed to evaluate the association between amino acid metabolic profile and bone indices in the elderly population. METHODS: 400 individuals were randomly selected from 2384 elderly men and women over 60 years participating in the second stage of the Bushehr elderly health (BEH) program, a population-based prospective cohort study that is being conducted in Bushehr, a southern province of Iran. Frozen plasma samples were used to measure 29 amino acid and derivatives metabolites using the UPLC-MS/MS-based targeted metabolomics platform. We conducted Elastic net regression analysis to detect the metabolites associated with BMD of different sites and lumbar spine trabecular bone score, and also to examine the ability of the measured metabolites to differentiate osteoporosis. RESULTS: We adjusted the analysis for possible confounders (age, BMI, diabetes, smoking, physical activity, vitamin D level, and sex). Valine, leucine, isoleucine, and alanine in women and tryptophan in men were the most important amino acids inversely associated with osteoporosis (OR range from 0.77 to 0.89). Sarcosine, followed by tyrosine, asparagine, alpha aminobutyric acid, and ADMA in women and glutamine in men and when both women and men were considered together were the most discriminating amino acids detected in individuals with osteoporosis (OR range from 1.15 to 1.31). CONCLUSION: We found several amino acid metabolites associated with possible bone status in elderly individuals. Further studies are required to evaluate the utility of these metabolites as clinical biomarkers for osteoporosis prediction and their effect on bone health as dietary supplements.

Evaluating the association between amino acid and acylcarnitine profiles and different levels of coronary artery disease risk in postmenopausal women using targeted metabolomics technique.

OBJECTIVES: Postmenopausal women are at increased risk of developing coronary artery disease (CAD). Metabolomic approaches aim at discovering more helpful biomarkers of CAD to reduce the disease burden in the future. Here, we intend to find potential blood biomarkers, amino acids, and acylcarnitines in postmenopausal women with different severity of CAD by using high-throughput methods. METHOD: This cross-sectional study was performed on postmenopausal women ( n = 183) who underwent coronary CT scans. Coronary artery calcium scoring (CACS) was assessed to detect plaque burden and degree of coronary artery obstruction. The participants were divided into three groups based on the score as follows (i) "low CACS" ( n = 96); a score of 0 to 10, (ii) "medium CACS" ( n = 35); a score between 11 and 100 and (iii) "high CACS" ( n = 52); a score greater than 100. Metabolites, including amino acids and acylcarnitines, were quantified using a targeted mass spectrometry method in serum samples. The association between metabolites and disease status was evaluated using univariate and multivariate regression analyses with adjustment for confounding factors. Factor analysis was used to deal with multiple comparisons. RESULTS: Metabolites, including proline, glutamic acid, and phenylalanine, were significantly lower in the high CACS group than the low CACS one. Also, a lower level of lysine and phenylalanine in high CACS compared with medium one was observed. Concerning acylcarnitines, it was found that C4 and C8:1 significantly were higher in women with high CACS. The logistic regression analysis revealed that the circulating levels of these metabolites (except C4) were associated with the presence of coronary artery calcification independently of age, body mass index, and time of menopause. Also, the amino acids were associated independently of medication and diabetes. CONCLUSIONS: The present study indicated that circulating levels of amino acids and acylcarnitines profile in postmenopausal women are partly associated with the severity of CAD in these participants.