|
1
|
Yang C, Chai X, Wang Y, Li D, Zhu D, Liang K, Wang J, Yang Z, Gong Q, Zhang J, Shao R. Atherogenic lipid parameters in people with normal glucose tolerance: implications from elevated 1-hour post-load plasma glucose. Cardiovasc Diabetol 2025; 24:207. [PMID: 40369580 PMCID: PMC12079842 DOI: 10.1186/s12933-025-02722-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/02/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are linked to an increased risk of cardiovascular disease (CVD). However, it remains unclear whether normal glucose tolerance (NGT) individuals with elevated 1-h PG (NGT-1hPG-high) should still be considered low-risk. Therefore, this study aims to demonstrate comprehensive lipid characteristics in individuals with different glycemic status stratified by 1-h PG, with a particular focus on those with NGT-1hPG-high. METHODS This cross-sectional study included individuals aged 25-55 years with high-risk of diabetes from the Daqing Diabetes Prevention Study II (Daqing DPS-II). Individuals were categorized into different glycemic status based on the World Health Organization's 1999 criteria and the International Diabetes Federation's 2024 position statement on 1-h PG. Traditional (TC, TG, HDL-C, LDL-C) and non-traditional lipid parameters [ApoA-1, ApoB, sdLDL-C, Lp(a), non-HDL-C, remnant cholesterol (RC), ApoB/ApoA-1, LDL-C/ApoB] were measured. Dyslipidemia was defined according to the 2023 Chinese Guidelines for Lipid Management. The China-PAR equation was used to estimate 10-year CVD risk. Spearman's correlation coefficients were calculated to evaluate the correlation between lipid parameters and 10-year CVD risk. Logistic and multiple linear regression models were performed to assess the association between 1-h PG and dyslipidemia as well as lipid parameters adjusting for covariates. RESULTS Among 2 469 individuals, 22.7% had NGT with normal 1-h PG (NGT-1hPG-normal), 19.9% had NGT-1hPG-high, 2.6% had prediabetes with normal 1-h PG (PDM-1hPG-normal), 34.2% had prediabetes with elevated 1-h PG (PDM-1hPG-high), and 20.6% had newly diagnosed diabetes. The prevalence of dyslipidemia did not significantly differ between NGT-1hPG-high and PDM-1hPG-high (OR = 1.13, 95%CI: 0.88-1.44, P > 0.05). Higher 1-h PG levels were consistently associated with an atherogenic lipid profile, characterized by increased TC, TG, LDL-C, ApoB, sdLDL-C, non-HDL-C, RC and ApoB/ApoA-1, along with decreased ApoA-1, HDL-C and LDL-C/ApoB (all P < 0.05). Among lipid parameters, TG, sdLDL-C, RC, ApoB/ApoA-1, LDL-C/ApoB and HDL-C showed the strongest correlation with 10-year CVD risk, with Spearman's correlation coefficients of 0.41, 0.38, 0.35, 0.31, - 0.37 and - 0.36, respectively. In the NGT-1hPG-high, TG, sdLDL-C, and ApoB/ApoA-1 levels were significantly higher, while HDL-C and LDL-C/ApoB levels were significantly lower compared to counterparts with NGT-1hPG-normal (all P < 0.05). Moreover, except for TG and RC (both P < 0.01), the majority of lipid parameter levels in NGT-1hPG-high did not significantly differ from those in PDM (all P > 0.05). CONCLUSIONS NGT-1hPG-high exhibited a similar atherogenic lipid profile to that observed in PDM. 1-h PG could serve as a potential indicator for the early identification of at-risk individuals who may otherwise go undetected among NGT population.
Collapse
Affiliation(s)
- Chunyu Yang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xin Chai
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Yachen Wang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Di Li
- Daqing Oilfield General Hospital (Daqing First Hospital), Daqing, 163000, China
| | - Dongli Zhu
- Daqing Oilfield General Hospital (Daqing First Hospital), Daqing, 163000, China
| | - Kaipeng Liang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Jinping Wang
- Daqing Oilfield General Hospital (Daqing First Hospital), Daqing, 163000, China
| | - Zhiwei Yang
- Daqing Oilfield General Hospital (Daqing First Hospital), Daqing, 163000, China
| | - Qiuhong Gong
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Juan Zhang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Ruitai Shao
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| |
Collapse
|
|
2
|
Rahman SS, Klamrak A, Nopkuesuk N, Nabnueangsap J, Janpan P, Choowongkomon K, Daduang J, Daduang S. Impacts of Plu kaow ( Houttuynia cordata Thunb.) Ethanolic Extract on Diabetes and Dyslipidemia in STZ Induced Diabetic Rats: Phytochemical Profiling, Cheminformatics Analyses, and Molecular Docking Studies. Antioxidants (Basel) 2024; 13:1064. [PMID: 39334723 PMCID: PMC11428413 DOI: 10.3390/antiox13091064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/24/2024] [Accepted: 08/27/2024] [Indexed: 09/30/2024] Open
Abstract
The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow (Houttuynia cordata Thunb.) ethanolic extract (PK) in streptozotocin (STZ) induced diabetic rats, focusing on its molecular mechanisms. Diabetes was induced in fasting Long Evans rats using streptozotocin (65 mg/kg b. w.), with glibenclamide (5 mg/kg/day) used as the standard experimental drug. The treated groups received oral supplementation of PK (500 mg/kg/day) for 28 days. The study evaluated blood glucose levels, lipid status, body weight, liver, kidney, and heart function biomarkers, antioxidant activity, and histological examination of various organs. Additionally, untargeted metabolomics, cheminformatics, and molecular docking were employed to elucidate the probable mechanisms of action of PK. Based on metabolomic profiling data, the PK was found to contain various putative antidiabetic agents such as kaempferol 7-neohesperidoside, isochlorogenic acid C, rutin, datiscin, and diosmin and they have been proposed to significantly (p < 0.001) reduce blood glucose levels and modulated hyperlipidemia. PK also improved the tested liver, kidney, and heart function biomarkers and reversed damage to normal pancreatic, liver, kidney, and heart cells in histological analysis. In conclusion, PK shows promise as a potential treatment or management option for diabetes and hyperlipidemia, as well as their associated complications in diabetic rats.
Collapse
Affiliation(s)
- Shaikh Shahinur Rahman
- Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
- Department of Applied Nutrition and Food Technology, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh
| | - Anuwatchakij Klamrak
- Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Napapuch Nopkuesuk
- Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Jaran Nabnueangsap
- Salaya Central Instrument Facility RSPG, Research Management and Development Division, Office of the President, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Piyapon Janpan
- Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Kiattawee Choowongkomon
- Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
| | - Jureerut Daduang
- Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sakda Daduang
- Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
- Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Khon Kaen University, Khon Kaen 40002, Thailand
| |
Collapse
|
|
3
|
Chowdhury K, Sinha S, Ahmad R, Lugova H, Mehta M, Kumar S, Haque M. Type 2 Diabetes Mellitus and Cardiometabolic Prospects: A Rapid Narrative Review. Cureus 2024; 16:e65808. [PMID: 39092382 PMCID: PMC11293072 DOI: 10.7759/cureus.65808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 07/30/2024] [Indexed: 08/04/2024] Open
Abstract
Cardiometabolic syndrome (CMS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases are among the major altruists to the international liability of disease. The lifestyle and dietary changes attributable to economic growth have resulted in an epidemiological transition towards non-communicable diseases (NCDs) as the leading causes of death. Low- and middle-income countries (LMICs) bear a more substantial disease burden due to limited healthcare sector capacities to address the rapidly growing number of chronic disease patients. The purpose of this narrative review paper was to explore the interrelationships between CMS, T2DM, and cardiovascular impairments in the context of NCDs, as well as major preventative and control interventions. The role of insulin resistance, hyperglycemia, and dyslipidemia in the pathogenesis of T2DM and the development of severe cardiovascular impairments was highlighted. This paper elaborated on the pivotal role of lifestyle modifications, such as healthy diets and physical activity, as cornerstones of addressing the epidemics of metabolic diseases. Foods high in calories, refined sugar, red meat, and processed and ready-to-eat meals were associated with an amplified risk of CMS and T2DM. In contrast, diets based on fruits, legumes, vegetables, and whole grain, home-cooked foods demonstrated protective effects against metabolic diseases. Additionally, the role of a psychological and behavioral approach in addressing metabolic diseases was highlighted, especially regarding its impact on patient empowerment and the patient-centered approach to preventative and therapeutic interventions.
Collapse
Affiliation(s)
- Kona Chowdhury
- Department of Pediatrics, Enam Medical College Hospital, Dhaka, BGD
| | - Susmita Sinha
- Department of Physiology, Enam Medical College Hospital, Dhaka, BGD
| | - Rahnuma Ahmad
- Department of Physiology, Medical College for Women and Hospital, Dhaka, BGD
| | - Halyna Lugova
- Department of Medicine and Health Sciences, UCSI (University College Sedaya International) University Bandar Springhill Campus, Port Dickson, MYS
| | - Miral Mehta
- Department of Pedodontics and Preventive Dentistry, Karnavati School of Dentistry, Karnavati University, Gandhinagar, IND
| | - Santosh Kumar
- Department of Periodontology and Implantology, Karnavati School of Dentistry, Karnavati University, Gandhinagar, IND
| | - Mainul Haque
- Department of Research, Karnavati Scientific Research Center (KSRC) School of Dentistry, Karnavati University, Gandhinagar, IND
- Department of Pharmacology and Therapeutics, National Defence University of Malaysia, Kuala Lumpur, MYS
| |
Collapse
|
|
4
|
Zhuang Y, Qiu L, Han D, Qiao Z, Wang F, Jiang Q, An Q, Li Y, Shangguan J, Bi X, Shen D. The association between triglyceride-glucose index and related parameters and risk of cardiovascular disease in American adults under different glucose metabolic states. Diabetol Metab Syndr 2024; 16:102. [PMID: 38760860 PMCID: PMC11100199 DOI: 10.1186/s13098-024-01340-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 04/29/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) encompasses an array of cardiac and vascular disorders, posing a significant threat to global health. It remains unclear whether there exists an association between triglyceride-glucose index (TyG) and its derived indices and the incidence of cardiovascular disease, and in particular, the strength of the association in populations with different glucose metabolisms is not known. METHODS Data extracted from the National Health and Nutrition Examination Survey (NHANES) covering the period from 1999 to 2020, involving a cohort of 14,545 participants, were leveraged for the analysis. Statistical assessments were executed utilizing R software, employing multivariable logistic regression models to scrutinize the correlation between TyG and its associated parameters with the incidence of cardiovascular disease across diverse glucose metabolism categories. Interaction analyses and restricted cubic splines were applied to evaluate potential heterogeneity in associations and investigate the link between TyG and its derivatives with the occurrence of cardiovascular disease. Furthermore, receiver operating characteristic curves were constructed to evaluate the extent of variability in the predictive performance of TyG and its derived parameters for cardiovascular disease across distinct glucose metabolic statuses. RESULTS This study found that TyG and its related parameters were differentially associated with the occurrence of cardiovascular disease in different glucose metabolic states. Curvilinear correlations were found between TyG in the IFG population and TyG-WC, TyG-BMI, and TyG-WHtR in the impaired glucose tolerance (IGT) population with the occurrence of cardiovascular disease. In addition, the introduction of TyG and its derived parameters into the classical Framingham cardiovascular risk model improved the predictive performance in different glucose metabolism populations. Among them, the introduction of TyG-WHtR in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), IFG & IGT and diabetes groups and TyG in the IGT group maximized the predictive power. CONCLUSIONS The findings provide new insights into the relationship between the TyG index and its derived parameters in different glucose metabolic states and the risk of cardiovascular disease, offering important reference value for future clinical practice and research. The study highlights the potential for improved risk stratification and prevention strategies based on TyG and its derived parameters.
Collapse
Affiliation(s)
- Yuansong Zhuang
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Liliang Qiu
- Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Dongjian Han
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Zhentao Qiao
- Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Fuhang Wang
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Qingjiao Jiang
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Quanxu An
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Yuhang Li
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Jiahong Shangguan
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Xuanye Bi
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China
| | - Deliang Shen
- Cardiology Department, First Affiliated Hospital of Zhengzhou University, Henan, China.
| |
Collapse
|
|
5
|
Kaul R, Paul P, Harfouche M, Saliba R, Chaari A. Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials. Diabetes Metab Res Rev 2024; 40:e3675. [PMID: 37381688 DOI: 10.1002/dmrr.3675] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 03/26/2023] [Accepted: 05/19/2023] [Indexed: 06/30/2023]
Abstract
AIMS Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.
Collapse
Affiliation(s)
- Ridhima Kaul
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Pradipta Paul
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Manale Harfouche
- Infectious Disease Epidemiology Group, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
- World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Reya Saliba
- Health Sciences Library, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Ali Chaari
- Premedical Division, Weill Cornell Medicine - Qatar, Qatar Foundation - Education City, Doha, Qatar
| |
Collapse
|
|
6
|
Chakraborty S, Verma A, Garg R, Singh J, Verma H. Cardiometabolic Risk Factors Associated With Type 2 Diabetes Mellitus: A Mechanistic Insight. Clin Med Insights Endocrinol Diabetes 2023; 16:11795514231220780. [PMID: 38148756 PMCID: PMC10750528 DOI: 10.1177/11795514231220780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 11/27/2023] [Indexed: 12/28/2023] Open
Abstract
A complex metabolic condition referred to as Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and decreased insulin production. Obesity, dyslipidemia, hypertension, and chronic inflammation are just a few of the cardiometabolic illnesses that people with T2DM are more likely to acquire and results in cardiovascular issues. It is essential to comprehend the mechanistic insights into these risk variables in order to prevent and manage cardiovascular problems in T2DM effectively. Impaired glycemic control leads to upregulation of De novo lipogenesis (DNL), promote hepatic triglyceride (TG) synthesis, worsening dyslipidemia that is accompanied by low levels of high density lipoprotein cholesterol (HDL-C) and high amounts of small, dense low-density lipoprotein cholesterol (LDL-C) further developing atherosclerosis. By causing endothelial dysfunction, oxidative stress, and chronic inflammation, chronic hyperglycemia worsens already existing cardiometabolic risk factors. Vasoconstriction, inflammation, and platelet aggregation are caused by endothelial dysfunction, which is characterized by decreased nitric oxide production, increased release of vasoconstrictors, proinflammatory cytokines, and adhesion molecules. The loop of IR and endothelial dysfunction is sustained by chronic inflammation fueled by inflammatory mediators produced in adipose tissue. Infiltrating inflammatory cells exacerbate inflammation and the development of plaque in the artery wall. In addition, the combination of chronic inflammation, dyslipidemia, and IR contributes to the emergence of hypertension, a prevalent comorbidity in T2DM. The ability to target therapies and management techniques is made possible by improvements in our knowledge of these mechanistic insights. Aim of present review is to enhance our current understanding of the mechanistic insights into the cardiometabolic risk factors related to T2DM provides important details into the interaction of pathophysiological processes resulting in cardiovascular problems. Understanding these pathways will enable us to create efficient plans for the prevention, detection, and treatment of cardiovascular problems in T2DM patients, ultimately leading to better overall health outcomes.
Collapse
Affiliation(s)
- Snigdha Chakraborty
- Overseas R & D Centre, Overseas HealthCare Pvt Ltd., Phillaur, Punjab, India
| | - Anjali Verma
- Department of Food Technology and Nutrition, School of Agriculture, Lovely Professional University, Phagwara, Punjab, India
| | - Rajeev Garg
- IKG Punjab Technical University, Kapurthala, India
- Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela, Ropar, Punjab, India
- Guru Nanak Institute of Pharmacy, Dalewal, Hoshiarpur, Punjab, India
| | - Jyoti Singh
- Department of Food Technology and Nutrition, School of Agriculture, Lovely Professional University, Phagwara, Punjab, India
| | - Hitesh Verma
- Overseas R & D Centre, Overseas HealthCare Pvt Ltd., Phillaur, Punjab, India
- IKG Punjab Technical University, Kapurthala, India
- Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela, Ropar, Punjab, India
- Biofern Life Sciences Pvt Ltd, Karnataka, India
| |
Collapse
|
|
7
|
Nemecz M, Stefan DS, Comarița IK, Constantin A, Tanko G, Guja C, Georgescu A. Microvesicle-associated and circulating microRNAs in diabetic dyslipidemia: miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 have biomarker potential. Cardiovasc Diabetol 2023; 22:260. [PMID: 37749569 PMCID: PMC10521428 DOI: 10.1186/s12933-023-01988-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 09/09/2023] [Indexed: 09/27/2023] Open
Abstract
BACKGROUND Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution. METHODS For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs. RESULTS The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels. CONCLUSIONS In conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology.
Collapse
Affiliation(s)
- Miruna Nemecz
- Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
| | - Diana Simona Stefan
- National Institute of Diabetes, Nutrition and Metabolic Disease 'Prof. Dr. Nicolae Constantin Paulescu', Bucharest, Romania
| | - Ioana Karla Comarița
- Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania
| | - Alina Constantin
- Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania
| | - Gabriela Tanko
- Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania
| | - Cristian Guja
- National Institute of Diabetes, Nutrition and Metabolic Disease 'Prof. Dr. Nicolae Constantin Paulescu', Bucharest, Romania
| | - Adriana Georgescu
- Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, Bucharest, Romania.
| |
Collapse
|
|
8
|
Lou K, Sun P, Zhang C, Jiang Q, Pang S. X-box binding protein 1: A new metabolic mediator and drug target of metformin? Front Pharmacol 2022; 13:1013218. [PMID: 36438823 PMCID: PMC9691898 DOI: 10.3389/fphar.2022.1013218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 10/17/2022] [Indexed: 11/13/2022] Open
Abstract
Accumulating evidence has demonstrated that metformin improved hypertriglyceridemia. The present study aim to investigate the molecular mechanism by which metformin improves hypertriglyceridemia via regulation of diacylglycerol O-acyltransferase 2 (DGAT2) and X-box binding protein 1 (XBP1) in the liver and whether AMP-activated protein kinase (AMPK) is involved. Mice were fed a high-fat diet (HFD) or high-fat diet with metformin for 5 weeks to evaluate the effect of metformin on triglyceride (TG) levels and expression of DGAT2 and XBP1 in the liver. In vitro HepG2 cells or XBP1 knockout AML12 hepatocytes were stimulated with metformin, palmitic acid or small interfering RNA inducing XBP1 knockdown, or dominant-negative mutant AMPK plasmid. Metformin treatment reduced hepatic TG levels in the liver of HFD-fed mice. Expression of nuclear and cytoplasmic XBP1 protein and its downstream target gene DGAT2 decreased in the liver of HFD-fed mice and HepG2 cells after metformin treatment. AMPK inactivation or overexpression of XBP1 attenuates this effect. Our preliminary results demonstrate that metformin activates AMPK to reduce TG synthesis by inhibiting the XBP1-mediated DGAT2 pathway, at least in part, suggesting that XBP1 is a new metabolic mediator for metformin treatment of hypertriglyceridemia and associated metabolic disease.
Collapse
Affiliation(s)
- Kai Lou
- Department of Endocrinology, Jinan Central Hospital, Shandong University, Jinan, China
- Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Pei Sun
- Department of Endocrinology, Jinan Central Hospital, Shandong University, Jinan, China
- Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Chunxue Zhang
- Department of Nuclear Medicine, Jinan Central Hospital, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Qiang Jiang
- Department of Endocrinology, Jinan Central Hospital, Shandong University, Jinan, China
- Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shuguang Pang
- Department of Endocrinology, Jinan Central Hospital, Shandong University, Jinan, China
- Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
- *Correspondence: Shuguang Pang,
| |
Collapse
|
|
9
|
Neves JS, Newman C, Bostrom JA, Buysschaert M, Newman JD, Medina JL, Goldberg IJ, Bergman M. Management of dyslipidemia and atherosclerotic cardiovascular risk in prediabetes. Diabetes Res Clin Pract 2022; 190:109980. [PMID: 35787415 DOI: 10.1016/j.diabres.2022.109980] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/26/2022] [Accepted: 06/29/2022] [Indexed: 11/03/2022]
Abstract
Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe. Although guidelines advocate aggressive management of lipid parameters in diabetes, most guidelines do not address treatment of dyslipidemia in prediabetes despite the increased atherosclerotic cardiovascular disease (ASCVD) risk. Several criteria are used to diagnose prediabetes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and HbA1c of 5.7-6.4%. Individuals with prediabetes have a greater risk of diabetes, a higher prevalence of dyslipidemia with a more atherogenic lipid profile and an increased risk of ASCVD. In addition to calculating ASCVD risk using traditional methods, an OGTT may further stratify risk. Those with 1-hour plasma glucose ≥8.6 mmol/L (155 mg/dL) and/or 2-hour ≥7.8 mmol/L (140 mg/dL) (IGT) have a greater risk of ASCVD. Diet and lifestyle modification are fundamental in prediabetes. Statins, ezetimibe and PCSK9 inhibitors are recommended in people requiring pharmacotherapy. Although high-intensity statins may increase risk of diabetes, this is acceptable because of the greater reduction of ASCVD. The LDL-C goal in prediabetes should be individualized. In those with IGT and/or elevated 1-hour plasma glucose, the same intensive approach to dyslipidemia as recommended for diabetes should be considered, particularly if other ASCVD risk factors are present.
Collapse
Affiliation(s)
- João Sérgio Neves
- Department of Endocrinology, Diabetes and Metabolism, São João University Hospital Center, Porto, Portugal; Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Connie Newman
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA
| | - John A Bostrom
- Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Martin Buysschaert
- Department of Endocrinology and Diabetology, Université Catholique de Louvain, University Clinic Saint-Luc, Brussels, Belgium
| | - Jonathan D Newman
- Division of Cardiology and the Center for the Prevention of Cardiovascular Disease, New York University Grossman School of Medicine, New York, NY, USA
| | | | - Ira J Goldberg
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA
| | - Michael Bergman
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA
| |
Collapse
|
|
10
|
Liu Y, Xiang H, Xiong W, Ouyang J, Liu H, Zhao S, Xiao J, Li J, Shu Z, Wang X, Liu H, Zhang J, Fan J, Li Y, Chen S, Lu H. Glucolipotoxicity induces endothelial cell dysfunction by activating autophagy and inhibiting autophagic flow. Diab Vasc Dis Res 2022; 19:14791641221102513. [PMID: 35549572 PMCID: PMC9125420 DOI: 10.1177/14791641221102513] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES This study aims to determine the role and mechanism of autophagy in endothelial cell dysfunction by glucolipotoxicity. METHODS Human umbilical vein endothelial cells (HUVECs) were treated with high glucose and high palmitic acid. The number of autophagosomes was evaluated by monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM). The expression of autophagy-related proteins (LC3 and P62) was assessed by Western blotting. Capillary tube-like formation was evaluated on Matrigel. Reactive oxygen species (ROS) production was detected by DCFH-DA. Cell apoptosis was measured by Hoechst 33258 staining and flow cytometry. Phosphorylation of AMPK, mTOR, and ULK1 was also analyzed by Western blotting. RESULTS We found that glucolipotoxicity induced autophagy initiation and hindered autophagosomes degradation. Moreover, glucolipotoxicity increased the production of intracellular ROS, decreased the ability of tubular formation, and increased cell apoptosis. However, endothelial cell dysfunction was alleviated by 3-methyladenine, an early-stage autophagy inhibitor. Additionally, glucolipotoxicity promoted the phosphorylation of AMPK and ULK1 and inhibited the phosphorylation of mTOR. CONCLUSIONS Glucolipotoxicity initiates autophagy through the AMPK/mTOR/ULK1 signaling pathway and inhibits autophagic flow, leading to the accumulation of autophagosomes, thereby inducing apoptosis and impairing endothelial cell function.
Collapse
Affiliation(s)
- Yulan Liu
- Health Management Center, Third Xiangya Hospital of Central
South University, Changsha, China
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Hong Xiang
- Center for Experimental Medicine, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Wenfang Xiong
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Jie Ouyang
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Hengdao Liu
- Department of Cardiology, The First Affiliated Hospital of
Zhengzhou University, Zhenzhou, China
| | - Shaoli Zhao
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Jie Xiao
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Jialing Li
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Zhihao Shu
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Xuewen Wang
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Huiqin Liu
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Jing Zhang
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Jianing Fan
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Ying Li
- Department of Cardiology, Third Xiangya Hospital of Central
South University, Changsha, China
| | - Shuhua Chen
- Departments of Biochemistry, School
of Life Sciences, Central South
University, Changsha, China
- Shuhua Chen, Department of Biochemistry,
School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha
410013, China.
| | - Hongwei Lu
- Health Management Center, Third Xiangya Hospital of Central
South University, Changsha, China
- Center for Experimental Medicine, Third Xiangya Hospital of Central
South University, Changsha, China
- Hongwei Lu, Center for Experimental
Medicine, Third Xiangya Hospital of Central South University, 138 Tongzipo Road,
Changsha 410013, China.
| |
Collapse
|
|
11
|
Garcia E, Shalaurova I, Matyus SP, Schutten JC, Bakker SJL, Dullaart RPF, Connelly MA. Nuclear Magnetic Resonance-Measured Ionized Magnesium Is Inversely Associated with Type 2 Diabetes in the Insulin Resistance Atherosclerosis Study. Nutrients 2022; 14:nu14091792. [PMID: 35565760 PMCID: PMC9103587 DOI: 10.3390/nu14091792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/05/2023] Open
Abstract
The aims were to optimize a nuclear magnetic resonance (NMR)-based assay for quantifying ionized or free magnesium and investigate its association with type 2 diabetes (T2D). A high-throughput, ionized magnesium assay was optimized and evaluated. Plasma magnesium was quantified, and associations with T2D were ascertained in Insulin Resistance Atherosclerosis Study (IRAS) participants. Coefficients of variation for the ionized magnesium assay ranged from 0.7−1.5% for intra-assay and 4.2−4.7% for inter-assay precision. In IRAS (n = 1342), ionized magnesium was significantly lower in subjects with prediabetes and T2D than in normoglycemic subjects, and lower in participants with T2D than those with prediabetes (p < 0.0001). Cross-sectional regression analyses revealed that magnesium was associated with T2D at baseline in models adjusted for multiple clinical risk factors (p = 0.032). This association appeared to be modified by sex, in such a way that the associations were present in women (OR = 0.54 (95% CI 0.37−0.79), p = 0.0015) and not in men (OR = 0.98 (95% CI 0.71−1.35), p = 0.90). Longitudinal regression analyses revealed an inverse association between magnesium and future T2D in the total population (p = 0.035) that was attenuated by LP-IR (p = 0.22). No interactions were detected between magnesium and age, race, BMI, glucose, insulin, triglycerides, or LPIR for the prospective association with future T2D. However, a significant interaction between magnesium and sex was present, now with a trend for an association in men (OR = 0.75 (95% CI 0.55−1.02), p = 0.065 and absence of an association in women (OR = 1.01 (0.76−1.33), p = 0.97). Conclusions: lower ionized magnesium, as measured by an NMR-based assay optimized for accuracy and precision, was associated cross-sectionally with T2D at baseline and longitudinally with incident T2D in IRAS.
Collapse
Affiliation(s)
- Erwin Garcia
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (I.S.); (S.P.M.)
| | - Irina Shalaurova
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (I.S.); (S.P.M.)
| | - Steven P. Matyus
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (I.S.); (S.P.M.)
| | - Joelle C. Schutten
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.C.S.); (S.J.L.B.)
| | - Stephan J. L. Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (J.C.S.); (S.J.L.B.)
| | - Robin P. F. Dullaart
- Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands;
| | - Margery A. Connelly
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (I.S.); (S.P.M.)
- Correspondence:
| |
Collapse
|
|
12
|
Chmiela T, Węgrzynek J, Kasprzyk A, Waksmundzki D, Wilczek D, Gorzkowska A. If Not Insulin Resistance so What? - Comparison of Fasting Glycemia in Idiopathic Parkinson's Disease and Atypical Parkinsonism. Diabetes Metab Syndr Obes 2022; 15:1451-1460. [PMID: 35586204 PMCID: PMC9109887 DOI: 10.2147/dmso.s359856] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/29/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Parkinson's disease (PD) is a synucleinopathy, which presents dysautonomia, as its common non-motor symptom. Some research suggests the existing interplay between the autonomic nervous system dysfunction and glucose metabolism dysregulation in PD. OBJECTIVE To determine the prevalence of metabolic disorders with particular emphasis on glucose metabolism in patients with PD and atypical parkinsonism (AP). PATIENTS AND METHODS A retrospective study was performed by analyzing 461 clinical data of consecutive patients diagnosed with PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) hospitalized from 2019 to 2021 in the authors' institution. The study group included 350 patients (303 PD, 14 MSA, 33 PSP), aged 65.8 ± 9.7 years (42% were female). Laboratory results (fasting glycemia, lipid parameters, TSH, homocysteine and vitamin D3 levels) were collected. The patient's clinical condition was assessed in III part of Unified Parkinson's Disease Rating Scale (UPDRS p. III), Hoehn-Yahr scale, Mini Mental State Examination (MMSE) and Beck Depression Inventory (BDI). RESULTS Impaired fasting glycemia (IGF) was more prevalent in PD than in the PSP (43.43% vs 18.18%; p = 0.043). Similarly, PD presented a higher level of fasting glycemia (102.4 ± 16.7 mg/dl vs 92.2 ± 16.1mg/dl; p = 0.042). According to lipid parameters, patients with PD showed lower LDL cholesterol (92.3 ± 44.3mg/dl vs 119 ± 61.0mg/dl; p = 0.016) and lower BMI compared to patients with PSP (26.1 ± 4.0kg/m2 vs 29.3 ± 4.4 kg/m2; p = 0.024), but there were no statistically significant differences in triglycerides (TG) and HDL cholesterol levels. Males with PD presented greater frequency of IFG (35.05% vs 50.6%; p = 0.042), higher fasting glycemia (99.1 ± 14.3mg/dl vs 103.7 ± 14.7mg/dl; p = 0.006), lower total cholesterol, HDL cholesterol, and BMI compared to women with PD. CONCLUSION Our investigation supports an association between synucleinopathies and glucose metabolism dysregulation.
Collapse
Affiliation(s)
- Tomasz Chmiela
- Department of Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
- Correspondence: Tomasz Chmiela, Department of Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland, Tel +48 32 789 46 01, Fax +48 32 789 45 55, Email
| | - Julia Węgrzynek
- Students’ Scientific Association, Department of Neurorehabilitation, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Amadeusz Kasprzyk
- Students’ Scientific Association, Department of Neurorehabilitation, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Damian Waksmundzki
- Students’ Scientific Association, Department of Neurorehabilitation, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Dawid Wilczek
- Students’ Scientific Association, Department of Neurorehabilitation, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Gorzkowska
- Department of Neurorehabilitation, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| |
Collapse
|
|
13
|
Puig-Jové C, Castelblanco E, Falguera M, Hernández M, Soldevila B, Julián MT, Teis A, Julve J, Barranco-Altirriba M, Franch-Nadal J, Puig-Domingo M, Ortega E, Amigó N, Alonso N, Mauricio D. Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2022; 75:22-30. [PMID: 33785266 DOI: 10.1016/j.rec.2021.02.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/18/2021] [Indexed: 12/25/2022]
Abstract
INTRODUCTION AND OBJECTIVES Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region. METHODS Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed. RESULTS Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile. CONCLUSIONS Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants.
Collapse
Affiliation(s)
- Carlos Puig-Jové
- Servicio de Endocrinología y Nutrición, Hospital Universitario e Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Esmeralda Castelblanco
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau e Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Mireia Falguera
- Instituto de Investigación Biomédica y Universidad de Lleida, Centro de Atención Primaria Cervera, Gerencia de Atención Primaria, Institut Català de la Salut, Lleida, Spain
| | - Marta Hernández
- Servicio de Endocrinología y Nutrición, Hospital Universitario Arnau de Vilanova e Instituto de Investigación Biomédica de Lleida (IRBLleida), Lleida, Spain
| | - Berta Soldevila
- Servicio de Endocrinología y Nutrición, Hospital Universitario e Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol, Badalona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
| | - María Teresa Julián
- Servicio de Endocrinología y Nutrición, Hospital Universitario e Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Albert Teis
- Servicio de Cardiología, Institut del Cor (iCor), Hospital Universitario Germans Trias i Pujol, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), Barcelona, Spain
| | - Josep Julve
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - María Barranco-Altirriba
- Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau e Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Josep Franch-Nadal
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Manel Puig-Domingo
- Servicio de Endocrinología y Nutrición, Hospital Universitario e Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol, Badalona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
| | - Emilio Ortega
- Servicio de Endocrinología y Nutrición, Hospital Cínico de Barcelona, Institut d'investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Núria Amigó
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Departamento de Ingeniería Electrónica y Automática, Universidad Rovira i Virgili, Instituto de Investigación Sanitaria Pere Virgili (IISPV), Tarragona, Spain
| | - Núria Alonso
- Servicio de Endocrinología y Nutrición, Hospital Universitario e Instituto de Investigación en Ciencias de la Salud Germans Trias i Pujol, Badalona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), Barcelona, Spain.
| | - Didac Mauricio
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau e Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Facultad de Medicina, Universidad de Vic - Universidad Central de Cataluña (UVic/UCC), Vic, Barcelona, Spain
| |
Collapse
|
|
14
|
|
|
15
|
Merrill AK, Anderson T, Conrad K, Marvin E, James-Todd T, Cory-Slechta DA, Sobolewski M. Protracted Impairment of Maternal Metabolic Health in Mouse Dams Following Pregnancy Exposure to a Mixture of Low Dose Endocrine-Disrupting Chemicals, a Pilot Study. TOXICS 2021; 9:346. [PMID: 34941779 PMCID: PMC8706199 DOI: 10.3390/toxics9120346] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/19/2021] [Accepted: 12/07/2021] [Indexed: 12/22/2022]
Abstract
Pregnancy, a period of increased metabolic demands coordinated by fluctuating steroid hormones, is an understudied critical window of disease susceptibility for later-life maternal metabolic health. Epidemiological studies have identified associations between exposures to various endocrine-disrupting chemicals (EDCs) with an increased risk for metabolic syndrome, obesity, and diabetes. Whether such adverse outcomes would be heightened by concurrent exposures to multiple EDCs during pregnancy, consistent with the reality that human exposures are to EDC mixtures, was examined in the current pilot study. Mouse dams were orally exposed to relatively low doses of four EDCs: (atrazine (10 mg/kg), bisphenol-A (50 µg/kg), perfluorooctanoic acid (0.1 mg/kg), 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.036 µg/kg)), or the combination (MIX), from gestational day 7 until birth or for an equivalent 12 days in non-pregnant females. Glucose intolerance, serum lipids, weight, and visceral adiposity were assessed six months later. MIX-exposed dams exhibited hyperglycemia with a persistent elevation in blood glucose two hours after glucose administration in a glucose tolerance test, whereas no such effects were observed in MIX-exposed non-pregnant females. Correspondingly, MIX dams showed elevated serum low-density lipoprotein (LDL). There were no statistically significant differences in weight or visceral adipose; MIX dams showed an average visceral adipose volume to body volume ratio of 0.09, while the vehicle dams had an average ratio of 0.07. Collectively, these findings provide biological plausibility for the epidemiological associations observed between EDC exposures during pregnancy and subsequent maternal metabolic dyshomeostasis, and proof of concept data that highlight the importance of considering complex EDC mixtures based of off common health outcomes, e.g., for increased risk for later-life maternal metabolic effects following pregnancy.
Collapse
Affiliation(s)
- Alyssa K. Merrill
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| | - Timothy Anderson
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| | - Katherine Conrad
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| | - Elena Marvin
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| | - Tamarra James-Todd
- Department of Environmental Health, Harvard University, Boston, MA 02115, USA;
| | - Deborah A. Cory-Slechta
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| | - Marissa Sobolewski
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA; (A.K.M.); (T.A.); (K.C.); (E.M.); (D.A.C.-S.)
| |
Collapse
|
|
16
|
C Thambiah S, Lai LC. Diabetic dyslipidaemia. Pract Lab Med 2021; 26:e00248. [PMID: 34368411 PMCID: PMC8326412 DOI: 10.1016/j.plabm.2021.e00248] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 05/16/2021] [Accepted: 07/14/2021] [Indexed: 12/22/2022] Open
Abstract
Diabetes mellitus (DM) is an escalating pandemic and an established cardiovascular risk factor. An important aspect of the interaction between DM and atherosclerotic cardiovascular disease (ASCVD) is diabetic dyslipidaemia, an atherogenic dyslipidaemia encompassing quantitative [hypertriglyceridaemia (hyperTG) and decreased high density lipoprotein cholesterol (HDL)] and qualitative [increased small dense low density lipoprotein cholesterol (sdLDL) particles, large very low density lipoprotein cholesterol (VLDL) subfraction (VLDL1) and dysfunctional HDL] modifications in lipoproteins. Much of the pathophysiology linking DM and dyslipidaemia has been elucidated. This paper aims to review the pathophysiology and management of diabetic dyslipidaemia with respect to ASCVD. Briefly, the influence of diabetic kidney disease on lipid profile and lipid changes causing type 2 diabetes mellitus are highlighted. Biomarkers of diabetic dyslipidaemia, including novel markers and clinical trials that have demonstrated that non-lipid and lipid lowering therapies can lower cardiovascular risk in diabetics are discussed. The stands of various international guidelines on lipid management in DM are emphasised. It is important to understand the underlying mechanisms of diabetic dyslipidaemia in order to develop new therapeutic strategies against dyslipidaemia and diabetes. The various international guidelines on lipid management can be used to tailor a holistic approach specific to each patient with diabetic dyslipidaemia.
Collapse
Affiliation(s)
- Subashini C Thambiah
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
| | | |
Collapse
|
|
17
|
Impact of Work and Recreational Physical Activity on Prediabetes Condition among U.S. Adults: NHANES 2015-2016. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18041378. [PMID: 33546150 PMCID: PMC7913268 DOI: 10.3390/ijerph18041378] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/15/2021] [Accepted: 01/20/2021] [Indexed: 12/15/2022]
Abstract
More minutes of physical activity (PA) accumulated during a day are associated with a lower risk of diabetes mellitus type 2. However, it is less known if distinct dimensions of PA can produce a different protective effect in the prevention of prediabetes. The aim of this study was to analyze the impact of work and recreational PA on prediabetes among U.S. adults during the period 2015–2016 using the National Health and Nutrition Examination Survey (NHANES) database. Individuals (n = 4481) with hemoglobin A1c (HbA1c) test values of 5.7% to 6.4% were included. A logistic regression multivariate-adjusted analysis was conducted to estimate the association between the odds ratios (ORs) and 95% confidence intervals (CIs) of prediabetes, with work and recreational PA. The prevalence of prediabetes among U.S. adults was lower in physically active individuals both at work (~24%) and recreational (~21%) physical activities compared to individuals who were not physically active (27 to 30%). Individuals lacking practice of recreational PA had a high risk of prediabetes (OR = 1.26, 95% CI: 1.080 to 1.466). PA may be a protective factor for prediabetes conditions depending on gender, age, ethnic group, waist circumference, and thyroid disease.
Collapse
|
|
18
|
Sampson M, Clark A, Bachmann M, Garner N, Irvine L, Howe A, Greaves C, Auckland S, Smith J, Turner J, Rea D, Rayman G, Dhatariya K, John WG, Barton G, Usher R, Ferns C, Pascale M. Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia: A Randomized Clinical Trial. JAMA Intern Med 2021; 181:168-178. [PMID: 33136119 PMCID: PMC7607494 DOI: 10.1001/jamainternmed.2020.5938] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
IMPORTANCE Nearly half of the older adult population has diabetes or a high-risk intermediate glycemic category, but we still lack trial evidence for effective type 2 diabetes prevention interventions in most of the current high-risk glycemic categories. OBJECTIVE To determine whether a group-based lifestyle intervention (with or without trained volunteers with type 2 diabetes) reduced the risk of progression to type 2 diabetes in populations with a high-risk glycemic category. DESIGN, SETTING, AND PARTICIPANTS The Norfolk Diabetes Prevention Study was a parallel, 3-arm, group-based, randomized clinical trial conducted with up to 46 months of follow-up from August 2011 to January 2019 at 135 primary care practices and 8 intervention sites in the East of England. We identified 141 973 people at increased risk of type 2 diabetes, screened 12 778 (9.0%), and randomized those with a high-risk glycemic category, which was either an elevated fasting plasma glucose level alone (≥110 and <126 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) or an elevated glycated hemoglobin level (≥6.0% to <6.5%; nondiabetic hyperglycemia) with an elevated fasting plasma glucose level (≥100 to <110 mg/dL). INTERVENTIONS A control arm receiving usual care (CON), a theory-based lifestyle intervention arm of 6 core and up to 15 maintenance sessions (INT), or the same intervention with support from diabetes prevention mentors, trained volunteers with type 2 diabetes (INT-DPM). MAIN OUTCOMES AND MEASURES Type 2 diabetes incidence between arms. RESULTS In this study, 1028 participants were randomized (INT, 424 [41.2%] [166 women (39.2%)]; INT-DPM, 426 [41.4%] [147 women (34.5%)]; CON, 178 [17.3%] [70 women (%39.3)]) between January 1, 2011, and February 24, 2017. The mean (SD) age was 65.3 (10.0) years, mean (SD) body mass index 31.2 (5) (calculated as weight in kilograms divided by height in meters squared), and mean (SD) follow-up 24.7 (13.4) months. A total of 156 participants progressed to type 2 diabetes, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%). There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51), but each intervention arm had significantly lower odds of type 2 diabetes (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01). The effect size was similar in all glycemic, age, and social deprivation groups, and intervention costs per participant were low at $153 (£122). CONCLUSIONS AND RELEVANCE The Norfolk Diabetes Prevention lifestyle intervention reduced the risk of type 2 diabetes in current high-risk glycemic categories. Enhancing the intervention with DPM did not further reduce diabetes risk. These translatable results are relevant for current diabetes prevention efforts. TRIAL REGISTRATION ISRCTN Registry Identifier: ISRCTN34805606.
Collapse
Affiliation(s)
- Michael Sampson
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England.,Norwich Medical School, University of East Anglia, Norwich, England
| | - Allan Clark
- Norwich Medical School, University of East Anglia, Norwich, England
| | - Max Bachmann
- Norwich Medical School, University of East Anglia, Norwich, England
| | - Nikki Garner
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Lisa Irvine
- Norwich Medical School, University of East Anglia, Norwich, England
| | - Amanda Howe
- Norwich Medical School, University of East Anglia, Norwich, England
| | - Colin Greaves
- School of Sport, Exercise & Rehabilitation Sciences, University of Birmingham, Birmingham, England.,University of Exeter Medical School, College of Medicine & Health, University of Exeter, Exeter, England
| | - Sara Auckland
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Jane Smith
- Norwich Medical School, University of East Anglia, Norwich, England.,University of Exeter Medical School, College of Medicine & Health, University of Exeter, Exeter, England
| | - Jeremy Turner
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Dave Rea
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Gerry Rayman
- Department of Diabetes and Endocrinology, Ipswich General Hospital, Ipswich, England
| | - Ketan Dhatariya
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - W Garry John
- Department Clinical Biochemistry, Norfolk and Norwich University Hospital NHS Trust, Norwich, England
| | - Garry Barton
- Norwich Medical School, University of East Anglia, Norwich, England
| | - Rebecca Usher
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Clare Ferns
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | - Melanie Pascale
- Elsie Bertram Diabetes Centre, Department of Diabetes and Endocrinology, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, England
| | | |
Collapse
|
|
19
|
Mancuso E, Mannino GC, Fuoco A, Leo A, Citraro R, Averta C, Spiga R, Russo E, De Sarro G, Andreozzi F, Sesti G. HDL (High-Density Lipoprotein) and ApoA-1 (Apolipoprotein A-1) Potentially Modulate Pancreatic α-Cell Glucagon Secretion. Arterioscler Thromb Vasc Biol 2020; 40:2941-2952. [PMID: 33086869 DOI: 10.1161/atvbaha.120.314640] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Subjects with low levels of HDL (high-density lipoprotein) and ApoA-1 (apolipoprotein A-1) have increased risk to develop type 2 diabetes. HDL levels are an independent predictor of β-cell function and positively modulate it. Type 2 diabetes is characterized by defects in both β and α-cell function, but the effect of HDL and ApoA1 on α-cell function is unknown. Approach and Results: We observed a significant negative correlation (r=-0.422, P<0.0001) between HDL levels and fasting glucagon in a cohort of 132 Italian subjects. In a multivariable regression analysis including potential confounders such as age, sex, BMI, triglycerides, total cholesterol, fasting and 2-hour postload glucose, and fasting insulin, the association between HDL and fasting glucagon remained statistically significant (β=-0.318, P=0.006). CD1 mice treated with HDL or ApoA-1 for 3 consecutive days showed a 32% (P<0.001) and 23% (P<0.05) reduction, respectively, in glucagon levels following insulin-induced hypoglycemia, compared with controls. Treatment of pancreatic αTC1 clone 6 cells with HDL or ApoA-1 for 24 hours resulted in a significant reduction of glucagon expression (P<0.04) and secretion (P<0.01) after an hypoglycemic stimulus and increased Akt (RAC-alpha serine/threonine-protein kinase) and FoxO1 (forkhead/winged helix box gene, group O-1) phosphorylation. Pretreatment with Akt inhibitor VIII, PI3K (phosphatidylinositol 3-kinase) inhibitor LY294002, and HDL receptor SCARB-1 (scavenger receptor class B type 1) inhibitor BLT-1 (block lipid transport-1) restored αTC1 cell response to low glucose levels. CONCLUSIONS These results support the notion that HDL and ApoA-1 modulate glucagon expression and secretion by binding their cognate receptor SCARB-1, and activating the PI3K/Akt/FoxO1 signaling cascade in an in vitro α-cell model. Overall, these results raise the hypothesis that HDL and ApoA-1 may have a role in modulating glucagon secretion.
Collapse
Affiliation(s)
- Elettra Mancuso
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Anastasia Fuoco
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Antonio Leo
- Department of Science of Health (A.L., R.C., E.R., G.D.S.), University Magna Graecia of Catanzaro, Italy
| | - Rita Citraro
- Department of Science of Health (A.L., R.C., E.R., G.D.S.), University Magna Graecia of Catanzaro, Italy
| | - Carolina Averta
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Rosangela Spiga
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Emilio Russo
- Department of Science of Health (A.L., R.C., E.R., G.D.S.), University Magna Graecia of Catanzaro, Italy
| | - Giovambattista De Sarro
- Department of Science of Health (A.L., R.C., E.R., G.D.S.), University Magna Graecia of Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences (E.M., G.C.M., A.F., C.A., R.S., F.A.), University Magna Graecia of Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Italy (G.S.)
| |
Collapse
|
|
20
|
Radwan E, Bakr MH, Taha S, Sayed SA, Farrag AA, Ali M. Inhibition of endoplasmic reticulum stress ameliorates cardiovascular injury in a rat model of metabolic syndrome. J Mol Cell Cardiol 2020; 143:15-25. [PMID: 32311415 DOI: 10.1016/j.yjmcc.2020.04.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 04/11/2020] [Accepted: 04/16/2020] [Indexed: 12/20/2022]
Abstract
Metabolic (Met) syndrome is characterized by hypertension, insulin resistance and dyslipidaemia with high risk of cardiovascular disease. Endoplasmic reticulum (ER) stress is a key contributor in the pathogenesis of Met syndrome. The current study investigates the effect of Tauroursodeoxycholate (TUDCA), an ER stress inhibitor, on Met syndrome-induced cardiovascular complications and the possible underlying signalling mechanisms. Met syndrome was induced in rats, which were then treated with TUDCA. Body weight, blood pressure, glucose tolerance and insulin tolerance tests were performed. ER stress, survival and oxidative stress markers were measured in heart and aorta tissue. The results showed that TUDCA improved metabolic parameters in rats with Met syndrome. Treatment mitigated the Met syndrome-induced cardiovascular complications through upregulating survival markers and downregulating ER and oxidative stress markers. These results highlight the protective effect of ER stress inhibition as a potential target in the management of cardiovascular complications associated with Met syndrome.
Collapse
Affiliation(s)
- Eman Radwan
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Marwa H Bakr
- Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Salma Taha
- Department of Cardiology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Sally A Sayed
- Department of Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Alshaimaa A Farrag
- Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Maha Ali
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.
| |
Collapse
|
|
21
|
Higgins V, Omidi A, Tahmasebi H, Asgari S, Gordanifar K, Nieuwesteeg M, Adeli K. Marked Influence of Adiposity on Laboratory Biomarkers in a Healthy Cohort of Children and Adolescents. J Clin Endocrinol Metab 2020; 105:dgz161. [PMID: 31845996 PMCID: PMC7077953 DOI: 10.1210/clinem/dgz161] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 10/26/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prevalence of pediatric obesity is increasing worldwide and strongly associates with metabolic abnormalities, including inflammation, insulin resistance, and dyslipidemia. This study assessed the influence of 3 measures of adiposity on levels of routinely assessed biochemical markers in apparently healthy children and adolescents. METHODS The influence of adiposity on 35 biochemical markers was examined in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents by comparing serum biomarker levels between subjects with a normal weight, overweight, and obese body mass index (BMI). The cohort comprised 1332 subjects 5.1 to 19.0 years of age with a BMI ranging from 13.4 to 65.0 kg/m2. The association between each biochemical marker and BMI, waist circumference, and waist-to-height ratio z-scores was assessed, while adjusting for age and sex. Reference intervals were established for all biochemical markers before and after removing overweight/obese subjects. RESULTS In children and adolescents, levels of 13 routinely assessed biochemical markers, including alanine aminotransferase, apolipoprotein B, complement components 3 and 4, cholinesterase, high sensitivity C-reactive protein, gamma-glutamyl transferase, haptoglobin, high-density lipoprotein cholesterol, iron, transferrin, triglycerides, and uric acid, were significantly different between BMI categories. BMI, waist circumference, and/or waist-to-height ratio were significantly associated with the serum concentration of 24 of the 35 markers examined, after adjusting for age and sex. CONCLUSIONS Excess adiposity significantly influences circulating levels of routinely assessed laboratory markers, most notably liver enzymes, lipids/lipoproteins, inflammatory markers, and uric acid in children and adolescents. Although it is unknown whether altered biochemical marker levels in subjects with overweight/obesity reflect health or indolent disease, clinicians should be aware of the effect of weight status on several laboratory tests.
Collapse
Affiliation(s)
- Victoria Higgins
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Arghavan Omidi
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Houman Tahmasebi
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Shervin Asgari
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Kian Gordanifar
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Michelle Nieuwesteeg
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Khosrow Adeli
- CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada
| |
Collapse
|
|
22
|
Garcia E, Shalaurova I, Matyus SP, Oskardmay DN, Otvos JD, Dullaart RP, Connelly MA. Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index. J Clin Med 2020; 9:jcm9020321. [PMID: 31979327 PMCID: PMC7074331 DOI: 10.3390/jcm9020321] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/09/2020] [Accepted: 01/21/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: β-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R2 = 0.996, 0.994, and 0.994 for β-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for β-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ≤0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and β-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. Conclusions: Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance.
Collapse
Affiliation(s)
- Erwin Garcia
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
- Correspondence: ; Tel.: +1-(919)-388-5551
| | - Irina Shalaurova
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
| | - Steven P. Matyus
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
| | - David N. Oskardmay
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
| | - James D. Otvos
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
| | - Robin P.F. Dullaart
- Department of Endocrinology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
| | - Margery A. Connelly
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC 27560, USA; (I.S.); (S.P.M.); (D.N.O.); (J.D.O.); (M.A.C.)
| |
Collapse
|
|
23
|
Sánchez E, Betriu À, López-Cano C, Hernández M, Fernández E, Purroy F, Bermúdez-López M, Farràs-Sallés C, Barril S, Pamplona R, Rius F, Hernández C, Simó R, Lecube A. Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project. Cardiovasc Diabetol 2019; 18:154. [PMID: 31729979 PMCID: PMC6857207 DOI: 10.1186/s12933-019-0962-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 11/02/2019] [Indexed: 12/23/2022] Open
Abstract
Background Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. Methods Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. Results Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. Conclusions The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner. Trial registration NCT03228459 (clinicaltrials.gov)
Collapse
Affiliation(s)
- Enric Sánchez
- Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research Group, IRBLleida, University of Lleida, Lleida, Spain
| | - Àngels Betriu
- Vascular and Renal Translational Research Group, IRBLleida, RedinRen-ISCIII, Lleida, Spain
| | - Carolina López-Cano
- Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research Group, IRBLleida, University of Lleida, Lleida, Spain
| | - Marta Hernández
- Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research Group, IRBLleida, University of Lleida, Lleida, Spain
| | - Elvira Fernández
- Vascular and Renal Translational Research Group, IRBLleida, RedinRen-ISCIII, Lleida, Spain
| | - Francisco Purroy
- Stroke Unit, University Hospital Arnau de Vilanova, Clinical Neurosciences Group. IRBLleida, University of Lleida, Lleida, Spain
| | | | - Cristina Farràs-Sallés
- Applied Epidemiology Research Group, IRBLleida, Lleida, Spain.,Unitat de Suport a la Recerca Lleida, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Silvia Barril
- Respiratory Department, University Hospital Arnau de Vilanova-Santa María, Translational Research in Respiratory Medicine, IRBLleida, University of Lleida, Lleida, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Reinald Pamplona
- Experimental Medicine Department, IRBLleida, University of Lleida, Lleida, Spain
| | - Ferran Rius
- Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research Group, IRBLleida, University of Lleida, Lleida, Spain
| | - Cristina Hernández
- Endocrinology and Nutrition Department, University Hospital Vall d'Hebron. Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08024, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Rafael Simó
- Endocrinology and Nutrition Department, University Hospital Vall d'Hebron. Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Autonomous University of Barcelona, Pg. Vall d'Hebron 119-129, 08024, Barcelona, Spain. .,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Albert Lecube
- Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research Group, IRBLleida, University of Lleida, Lleida, Spain. .,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | | |
Collapse
|
|
24
|
Rai SK, Kashid M, Chakrabarty B, Upreti V, Shaki O. Is it necessary to screen patient with adhesive capsulitis of shoulder for diabetes mellitus? J Family Med Prim Care 2019; 8:2927-2932. [PMID: 31681669 PMCID: PMC6820405 DOI: 10.4103/jfmpc.jfmpc_244_19] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 03/25/2019] [Accepted: 04/06/2019] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Idiopathic adhesive capsulitis of shoulder is common cause of pain and restriction of shoulder motion between the ages of 30 and 65. The prevalence of adhesive capsulitis is as high as 10% to 22% in diabetes mellitus as compared normal population which is 02% and 04%. Therefore, the doubt arises whether patients developed adhesive capsulitis are at greater risk to develop diabetes mellitus and should be screen for diabetes so that it can be detected early. PURPOSE To compare the prevalence of prediabeties and diabetes mellitus among patients with features of idiopathic adhesive capsulitis of shoulder who are otherwise healthy. METHODS Patients between 30-65 years of age who attended Orthopaedics OPD with features of idiopathic adhesive capsulitis of shoulder were included. Participated underwent a 2 hour long oral glucose tolerance test and based on fasting and 2-hour plasma glucose levels, patients were diagnosed as normal glucose tolerance, prediabetic, or diabetic and the results were matched with previous published data. RESULTS 135 patients as participated and completed the test. 21 (15.5%) patients with idiopathic adhesive capsulitis of shoulder were found to be prediabetic, and 37 (27.4%) patients were found to be diabetic. However, 31 patients had family history of diabetes. CONCLUSION Based on our study, we can recommend that patients with features of idiopathic adhesive capsulitis of shoulder should be screened at least for fasting and post prandial blood sugar so that diabetes can be detected early.
Collapse
Affiliation(s)
- S. K. Rai
- Department of Orthopaedics, 151 Base Hospital, Guwahati, Assam, India
| | - Manoj Kashid
- Department of Orthopaedics, SMBT Medical Colleges, Igatpuri, Nasik, Maharashtra, India
| | | | - Vimal Upreti
- Department of Medicine, 151 Base Hospital, Guwahati, Assam, India
| | - Omna Shaki
- Department of Trauma & Emergency, 151 Base Hospital, Guwahati, Assam, India
| |
Collapse
|
|
25
|
Gupta M, Tummala R, Ghosh RK, Blumenthal C, Philip K, Bandyopadhyay D, Ventura H, Deedwania P. An update on pharmacotherapies in diabetic dyslipidemia. Prog Cardiovasc Dis 2019; 62:334-341. [PMID: 31442512 DOI: 10.1016/j.pcad.2019.07.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 07/28/2019] [Indexed: 01/08/2023]
Abstract
Hyperlipidemia plays a crucial role in the underlying pathogenesis of multiple cardiovascular diseases (CVD), including coronary artery disease, peripheral arterial disease, carotid stenosis, and heart failure. The risk of developing such diseases in the diabetic population is relatively high. Diabetes mellitus (DM) is an independent risk factor for premature atherosclerosis. The hallmark of DM dyslipidemia is a demonstrably high level of atherogenic triglyceride rich lipids including very low-density lipoprotein, chylomicrons, and small dense low-density lipoprotein (LDL). Moderate to high intensity statins, targeting LDL cholesterol reduction, remain the cornerstone in the management of this unique disorder. Many 'non-statin' drugs have recently been studied in the DM patients who were either on a 'maximally tolerated statin' or 'statin intolerant'. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are particularly important and were incorporated in the recent guidelines by the European Society of Cardiology, American College of Cardiology, American Heart Association, and American Diabetes Association. Icosapent Ethyl has garnered huge interest this year following publication of the REDUCE-IT trial. There are several newer hypolipidemic drugs, including Bempedoic acid, Inclisiran and RVX-208, that are in different phases of clinical trials. In this article, we review the underlying pathophysiology of DM dyslipidemia, existing guidelines related to its management, and the potential of newer hypolipidemic and anti-inflammatory drugs being incorporated in the management of DM.
Collapse
Affiliation(s)
- Manasvi Gupta
- Department of Internal Medicine, University of Connecticut, Hartford, CT, USA
| | | | - Raktim K Ghosh
- MedStar Heart and Vascular Institute, Union Memorial Hospital, Baltimore, MD, USA.
| | - Colin Blumenthal
- Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Karan Philip
- Department of Neurology, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Dhrubajyoti Bandyopadhyay
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/Mount Sinai St Luke's Roosevelt Hospital, New York, NY, USA
| | - Hector Ventura
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, USA
| | - Prakash Deedwania
- Department of Cardiology/Internal Medicine, University of California at San Francisco School of Medicine, San Francisco, CA, USA
| |
Collapse
|
|
26
|
Mahat RK, Singh N, Arora M, Rathore V. Health risks and interventions in prediabetes: A review. Diabetes Metab Syndr 2019; 13:2803-2811. [PMID: 31405710 DOI: 10.1016/j.dsx.2019.07.041] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 07/23/2019] [Indexed: 01/03/2023]
Abstract
Prediabetes is a condition which appears prior to the development of diabetes in which blood glucose is abnormally high but do not reach the diagnostic threshold of type 2 diabetes mellitus. It is characterized by a cluster of metabolic abnormalities viz. dysglycemia, dyslipidemia, hypertension, physical inactivity, obesity, insulin resistance, procoagulant state, endothelial dysfunction, oxidative stress and inflammation, placing prediabetic subjects to an increased risk for diabetes and its complications. Recent studies demonstrate that complications of diabetes i.e. microvascular and macrovascular complications may manifest in some prediabetic subjects. This article reviews prediabetes-related risk factors and health issues. In addition, this article also highlights the interventions to prevent the development of diabetes in prediabetic subjects.
Collapse
Affiliation(s)
- Roshan Kumar Mahat
- Department of Biochemistry, Gajra Raja Medical College, Jiwaji University, Gwalior, Madhya Pradesh, 474009, India; Department of Biochemistry, Muzaffarnagar Medical College, Muzaffarnagar, Uttar Pradesh, 251203, India.
| | | | - Manisha Arora
- Department of Biochemistry, Muzaffarnagar Medical College, Muzaffarnagar, Uttar Pradesh, 251203, India
| | - Vedika Rathore
- Department of Biochemistry, Shyam Shah Medical College, Rewa, Madhya Pradesh, 486001, India
| |
Collapse
|
|
27
|
Jialal I, Singh G. Management of diabetic dyslipidemia: An update. World J Diabetes 2019; 10:280-290. [PMID: 31139315 PMCID: PMC6522756 DOI: 10.4239/wjd.v10.i5.280] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/13/2019] [Accepted: 05/13/2019] [Indexed: 02/05/2023] Open
Abstract
Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride level, decreased high-density lipoprotein-cholesterol levels and increase in small dense low-density lipoprotein (LDL) particles. It is extremely common in type 2 diabetes (T2DM) affecting around 70 % of patients. Diabetic is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) which is the most common cause of death in the United States and LDL-cholesterol is the number 1 predictor of ASCVD events in T2DM. The purpose of this review is to discuss the pathophysiology and treatment of diabetic dyslipidemia. In this review, we have discussed both non-pharmacological and pharmacological treatment modalities including major treatment trials which have impacted the cardiovascular outcomes in patients with diabetes. Statin therapy is the mainstay of treatment to reduce ASCVD by decreasing LDL-C by 30%-49% or at least 50% depending on risk level. Attractive adjunctive therapies include Ezetimibe which is more cost effective and PCSK9 inhibitors which display potent LDL-cholesterol lowering and ASCVD event reduction. For severe hypertriglyceridemia, to avert the risk of pancreatitis, both fish oil and fenofibrate in concert with diet is the best strategy.
Collapse
Affiliation(s)
- Ishwarlal Jialal
- California North-state University College of Medicine, VA Medical Center, Mather, CA 95757, United States
| | - Gurdeep Singh
- Lady of Lourdes Memorial Hospital, New York, NY 10041, United States
| |
Collapse
|
|
28
|
Prediabetes and Outcome of Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-analysis. J Stroke Cerebrovasc Dis 2019; 28:683-692. [DOI: 10.1016/j.jstrokecerebrovasdis.2018.11.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 10/31/2018] [Accepted: 11/06/2018] [Indexed: 01/02/2023] Open
|
|
29
|
Manninen SM, Lankinen MA, de Mello VD, Laaksonen DE, Schwab US, Erkkilä AT. Intake of Fatty Fish Alters the Size and the Concentration of Lipid Components of HDL Particles and Camelina Sativa Oil Decreases IDL Particle Concentration in Subjects with Impaired Glucose Metabolism. Mol Nutr Food Res 2018; 62:e1701042. [PMID: 29645359 DOI: 10.1002/mnfr.201701042] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/26/2018] [Indexed: 11/08/2022]
Abstract
SCOPE Intake of long-chain n-3 PUFAs affects the lipoprotein subclass profile, whereas the effect of shorter chain n-3 PUFAs remains unclear. We investigated the effect of fish and camelina sativa oil (CSO) intakes on lipoprotein subclasses. METHODS AND RESULTS Altogether, 79 volunteers with impaired glucose metabolism were randomly assigned to CSO, fatty fish (FF), lean fish (LF), or control group for 12 weeks. Nuclear magnetic resonance spectroscopy was used to determine lipoprotein subclasses and their lipid components. The average HDL particle size increased in the FF group (overall p = 0.032) as compared with the control group. Serum concentrations of cholesterol in HDL and HDL2 (overall p = 0.024 and p = 0.021, respectively) and total lipids and phospholipids in large HDL particles (overall p = 0.012 and p = 0.019, respectively) increased in the FF group, differing significantly from the LF group. The concentration of intermediate-density lipoprotein (IDL) particles decreased in the CSO group (overall p = 0.033) as compared with the LF group. CONCLUSION Our study suggests that FF intake causes a shift toward larger HDL particles and increases the concentration of lipid components in HDL, which may be associated with the antiatherogenic properties of HDL. Furthermore, CSO intake decreases IDL particle concentration. These changes may favorably affect cardiovascular risk.
Collapse
Affiliation(s)
- Suvi M Manninen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland
| | - Maria A Lankinen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland
| | - Vanessa D de Mello
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland
| | - David E Laaksonen
- Institute of Clinical medicine, Internal Medicine, Kuopio University Hospital, 70029, Kuopio, Finland.,Institute of Biomedicine, Physiology, University of Eastern Finland, 70211, Kuopio, Finland
| | - Ursula S Schwab
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland.,Institute of Clinical medicine, Internal Medicine, Kuopio University Hospital, 70029, Kuopio, Finland
| | - Arja T Erkkilä
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland
| |
Collapse
|
|
30
|
Trouwborst I, Bowser SM, Goossens GH, Blaak EE. Ectopic Fat Accumulation in Distinct Insulin Resistant Phenotypes; Targets for Personalized Nutritional Interventions. Front Nutr 2018; 5:77. [PMID: 30234122 PMCID: PMC6131567 DOI: 10.3389/fnut.2018.00077] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 08/15/2018] [Indexed: 12/13/2022] Open
Abstract
Cardiometabolic diseases are one of the leading causes for disability and mortality in the Western world. The prevalence of these chronic diseases is expected to rise even further in the next decades. Insulin resistance (IR) and related metabolic disturbances are linked to ectopic fat deposition, which is the storage of excess lipids in metabolic organs such as liver and muscle. Notably, a vicious circle exists between IR and ectopic fat, together increasing the risk for the development of cardiometabolic diseases. Nutrition is a key-determining factor for both IR and ectopic fat deposition. The macronutrient composition of the diet may impact metabolic processes related to ectopic fat accumulation and IR. Interestingly, however, the metabolic phenotype of an individual may determine the response to a certain diet. Therefore, population-based nutritional interventions may not always lead to the most optimal (cardiometabolic) outcomes at the individual level, and differences in the metabolic phenotype may underlie conflicting findings related to IR and ectopic fat in dietary intervention studies. Detailed metabolic phenotyping will help to better understand the complex relationship between diet and metabolic regulation, and to optimize intervention outcomes. A subgroup-based approach that integrates, among others, tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota, age, sex, ethnicity, and psychological factors may thereby increase the efficacy of dietary interventions. Nevertheless, the implementation of more personalized nutrition may be complex, costly, and time consuming. Future studies are urgently warranted to obtain insight into a more personalized approach to nutritional interventions, taking into account the metabolic phenotype to ultimately improve insulin sensitivity and reduce the risk for cardiometabolic diseases.
Collapse
Affiliation(s)
- Inez Trouwborst
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Suzanne M Bowser
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Gijs H Goossens
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Ellen E Blaak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands
| |
Collapse
|
|
31
|
Wolak-Dinsmore J, Gruppen EG, Shalaurova I, Matyus SP, Grant RP, Gegen R, Bakker SJL, Otvos JD, Connelly MA, Dullaart RPF. A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness. Clin Biochem 2018; 54:92-99. [PMID: 29432757 DOI: 10.1016/j.clinbiochem.2018.02.001] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 12/22/2017] [Accepted: 02/03/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Plasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. DESIGN AND METHODS The performance of the NMR-based BCAA assay was evaluated. A method comparison study was performed with mass spectrometry (LC-MS/MS). Plasma BCAA were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1209; 376 T2DM subjects) and in a Groningen cohort (n = 123; 67 T2DM subjects). In addition, carotid intima media thickness (cIMT) was measured successfully in 119 subjects from the Groningen cohort. RESULTS NMR-based BCAA assay results were linear over a range of concentrations. Coefficients of variation for inter- and intra-assay precision ranged from 1.8-6.0, 1.7-5.4, 4.4-9.1, and 8.8-21.3%, for total BCAA, valine, leucine, and isoleucine, respectively. BCAA quantified from the same samples using NMR and LC-MS/MS were highly correlated (R2 = 0.97, 0.95 and 0.90 for valine, leucine and isoleucine). In both cohorts total and individual BCAA were elevated in T2DM (P = 0.01 to ≤0.001). Moreover, cIMT was associated with BCAA independent of age, sex, T2DM and metabolic syndrome (MetS) categorization or alternatively of individual MetS components. CONCLUSIONS BCAA levels, measured by NMR in the clinical laboratory, are elevated in T2DM and may be associated with cIMT, a proxy of subclinical atherosclerosis.
Collapse
Affiliation(s)
| | - Eke G Gruppen
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
| | - Irina Shalaurova
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Steven P Matyus
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Russell P Grant
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Ray Gegen
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Stephan J L Bakker
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
| | - James D Otvos
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Margery A Connelly
- Laboratory Corporation of America Holdings (LabCorp), Morrisville, Burlington, NC, USA.
| | - Robin P F Dullaart
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| |
Collapse
|
|
32
|
Hämäläinen P, Saltevo J, Kautiainen H, Mäntyselkä P, Vanhala M. Hemoglobin level and lipoprotein particle size. Lipids Health Dis 2018; 17:10. [PMID: 29321013 PMCID: PMC5764014 DOI: 10.1186/s12944-018-0655-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 01/02/2018] [Indexed: 12/28/2022] Open
Abstract
Background Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size. Methods We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy. Results Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05). Conclusion Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.
Collapse
Affiliation(s)
- Päivi Hämäläinen
- Department of Internal Medicine, Tampere University Hospital, Teiskontie 35, 33521, Tampere, Finland.
| | - Juha Saltevo
- Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland
| | - Hannu Kautiainen
- Unit of Family Practice, Central Finland Central Hospital, Jyväskylä, Finland.,Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland
| | - Pekka Mäntyselkä
- Unit of Primary Health Care, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland
| | - Mauno Vanhala
- Unit of Family Practice, Central Finland Central Hospital, Jyväskylä, Finland.,University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| |
Collapse
|
|
33
|
Zhang Z, Fang P, Yu M, Wang Y, Li Y, Shi M, Bo P, Gu X, Zhu Y. Serum Galanin Concentration is Increased in Subjects with Impaired Glucose Tolerance. Can J Diabetes 2017; 41:563-566. [PMID: 28416367 DOI: 10.1016/j.jcjd.2017.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Revised: 12/10/2016] [Accepted: 01/03/2017] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Although extensive data have shown that galanin can regulate the food intake and glucose metabolism of animals, little is known regarding the galanin concentration in patients with impaired glucose tolerance (IGT). Therefore, the aims of this study were to investigate whether serum galanin levels and other metabolic parameters are changed in patients with IGT compared with controls with normal glucose tolerance (NGT). METHODS Data regarding serum galanin levels and relative metabolic parameters were collected in 12 patients with IGT and 12 healthy patients with NGT. RESULTS At 1 hour and 2 hours after dinner, serum galanin, insulin and glucose levels were significantly higher in patients with IGT than in controls with NGT. Additionally, the body weights of patients with IGT was higher than those of the controls. Furthermore, a negative correlation was found between galanin levels and 1-hour glucose concentrations (r=-0.580; p=0.048) in patients with IGT. CONCLUSIONS The higher serum galanin levels as well as the negative correlation between galanin levels and 1-hour glucose content in patients with IGT may result from the interaction between insulin and galanin in differing conditions, suggesting that the galanin level may be used as a potential biomarker for the prediction of IGT in clinical settings.
Collapse
Affiliation(s)
- Zhenwen Zhang
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Penghua Fang
- Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, China
| | - Mei Yu
- Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China
| | - Yan Wang
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Yin Li
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Mingyi Shi
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, China
| | - Ping Bo
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, China
| | - Xuewen Gu
- Department of Pathology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
| | - Yan Zhu
- Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, China
| |
Collapse
|
|
34
|
Laaksonen J, Taipale T, Seppälä I, Raitoharju E, Mononen N, Lyytikäinen LP, Waldenberger M, Illig T, Hutri-Kähönen N, Rönnemaa T, Juonala M, Viikari J, Kähönen M, Raitakari O, Lehtimäki T. Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study. Diabetes Metab Res Rev 2017; 33. [PMID: 28609607 DOI: 10.1002/dmrr.2914] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 04/21/2017] [Accepted: 05/22/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PRD ) and without dyslipidaemia (PR0 ) and compared these to nonprediabetic controls without dyslipidaemia (C0 ). METHODS The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years. Genome-wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes. RESULTS Pathways for cholesterol synthesis, interleukin-12-mediated signalling events, and downstream signalling in naïve CD8+ T-cells were upregulated in the PR0 group in comparison with controls (C0 ). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T-cell signalling and interleukin-12-mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR0 and PRD ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PRD group was compared with the C0 group. Five genes in the PR0 group and 1 in the PRD group were significantly differentially expressed in comparison with the C0 group. CONCLUSIONS Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined.
Collapse
Affiliation(s)
- Jaakko Laaksonen
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Tuukka Taipale
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Ilkka Seppälä
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Emma Raitoharju
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Nina Mononen
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Melanie Waldenberger
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany
| | - Thomas Illig
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, München, Germany
- Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
- Institute for Human Genetics, Hannover Medical School, Hannover, Germany
| | - Nina Hutri-Kähönen
- Department of Paediatrics, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Tapani Rönnemaa
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
| | - Markus Juonala
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
| | - Jorma Viikari
- Department of Medicine, University of Turku, Turku, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
| | - Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Olli Raitakari
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, University of Turku, Turku, Finland
- Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| |
Collapse
|
|
35
|
Family history of type 2 diabetes, abdominal adipocyte size and markers of the metabolic syndrome. Int J Obes (Lond) 2017; 41:1621-1626. [PMID: 28736442 PMCID: PMC5818259 DOI: 10.1038/ijo.2017.171] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 06/27/2017] [Accepted: 07/11/2017] [Indexed: 02/06/2023]
Abstract
Background/Objectives A major risk factor of type 2 diabetes mellitus (T2DM) is a positive family history of diabetes. First degree relatives (FDR) of patients with T2DM are more insulin resistant and are reported to have larger abdominal subcutaneous adipocytes than adults without a family history. Our objectives were to assess whether a family history of T2DM is associated with larger abdominal adipocytes independent of age, sex, and abdominal subcutaneous fat and to assess whether FDR of T2DM is also independently related to femoral adipocyte size, as well as visceral fat and fasting plasma triglyceride (TG) concentrations. Methods We extracted adipocyte size, body composition, plasma TG and demographic data of non-diabetic research participants of previous studies conducted in our laboratory. We ascertained the family history of T2DM from the electronic medical records. Multivariate regression analysis was used to assess whether FDR of T2DM are more likely to have other risk factors after adjusting for known covariates. Results Of 604 participants, 148 were a FDR of T2DM. Although abdominal and femoral adipocyte size was greater in FDR of T2DM than those without a family history (0.74 ± 0.33 vs 0.63 ± 0.33 µg lipid/cell, P < 0.001; 0.81 ± 0.29 vs 0.72 ± 0.33 µg lipid/cell, P=0.01, respectively), this was confounded by FDR of T2DM being older, having greater BMI’s and percent body fat. A family history of T2DM was a significant predictor of abdominal adipocyte size after adjustment for age and body fat distribution parameters in females (total R2=0.5, p < 0.0001), but not in males. A family history of T2DM was not independently predictive of femoral adipocyte size, visceral fat area or TG. Conclusions FDR of T2DM females have larger abdominal, but not femoral, adipocytes, even after accounting for age and body fat distribution.
Collapse
|
|
36
|
Momtazi AA, Banach M, Pirro M, Stein EA, Sahebkar A. PCSK9 and diabetes: is there a link? Drug Discov Today 2017; 22:883-895. [DOI: 10.1016/j.drudis.2017.01.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 12/08/2016] [Accepted: 01/10/2017] [Indexed: 12/14/2022]
|
|
37
|
Shinnakasu A, Yamamoto K, Kurano M, Arimura H, Arimura A, Kikuti A, Hashiguchi H, Deguchi T, Nishio Y. The Combination Therapy of Fenofibrate and Ezetimibe Improved Lipid Profile and Vascular Function Compared with Statins in Patients with Type 2 Diabetes. J Atheroscler Thromb 2017; 24:735-748. [PMID: 28450679 PMCID: PMC5517547 DOI: 10.5551/jat.39446] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
AIM Elevated level of serum triglyceride (TG) is a characteristic of type 2 diabetes. We evaluated the clinical significance of intervention for the serum TG levels in the fasting and postprandial states in patients with type 2 diabetes. METHODS Fifty patients with type 2 diabetes, treated with statins, were selected and divided into two groups. One group was treated with a combination of fenofibrate and ezetimibe (F/E group) and the other group with statins (statin group) for 12 weeks. The lipoprotein profile of both groups was compared using high-performance liquid chromatography, and the vascular function was assessed using flow-mediated dilation (FMD) at the forearm. RESULTS The levels of very low-density lipoprotein (VLDL) cholesterol, malondialdehyde low-density lipoprotein (MDA-LDL), total TG, chylomicron-TG, VLDL-TG, and HDL-TG decreased in the F/E group, whereas those of HDL cholesterol increased. Furthermore, the peak particle size of LDL increased, but that of HDL decreased in the F/E group. The combination treatment significantly improved the FMD. The change in the cholesterol level in a very small fraction of HDL was a significant independent predictor for determining the improvement of FMD (p＜0.01). CONCLUSIONS Compared with the treatment with statins, the treatment with the combination of fenofibrate and ezetimibe effectively controlled the LDL cholesterol and TG levels, increased the HDL cholesterol level, especially in its small fraction, and improved vascular function of patients with type 2 diabetes.
Collapse
Affiliation(s)
- Atsushi Shinnakasu
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Kiyoaki Yamamoto
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Mihoko Kurano
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Hiroshi Arimura
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Aiko Arimura
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Akira Kikuti
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Hiroshi Hashiguchi
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Takahisa Deguchi
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| | - Yoshihiko Nishio
- Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
| |
Collapse
|
|
38
|
Di Bonito P, Pacifico L, Chiesa C, Valerio G, Miraglia Del Giudice E, Maffeis C, Morandi A, Invitti C, Licenziati MR, Loche S, Tornese G, Franco F, Manco M, Baroni MG. Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity. J Endocrinol Invest 2017; 40:409-416. [PMID: 27854028 DOI: 10.1007/s40618-016-0576-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/03/2016] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). METHODS Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. RESULTS The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. CONCLUSIONS Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.
Collapse
Affiliation(s)
- P Di Bonito
- Department of Internal Medicine, "S. Maria delle Grazie", Pozzuoli Hospital, Naples, Italy
| | - L Pacifico
- Policlinico Umberto I Hospital, Sapienza University of Rome, 00161, Rome, Italy.
| | - C Chiesa
- Institute of Translational Pharmacology, National Research Council, Rome, Italy
| | - G Valerio
- Department of Movement and Wellness Sciences, Parthenope University, Naples, Italy
| | - E Miraglia Del Giudice
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, Naples, Italy
| | - C Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - A Morandi
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - C Invitti
- Department of Medical Sciences and Rehabilitation, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - M R Licenziati
- Department of Pediatrics, AORN Santobono-Pausilipon, Naples, Italy
| | - S Loche
- Pediatric Endocrine Unit, Regional Hospital for Microcitemia, Cagliari, Italy
| | - G Tornese
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy
| | - F Franco
- Pediatric Unity, AOU Udine, Udine, Italy
| | - M Manco
- IRCCS Bambino Gesù Children's Hospital, Rome, Italy
| | - M G Baroni
- Department of Medical Sciences, University of Cagliari, Cagliari, Italy
- Endocrinology, Department Experimental Medicine, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
39
|
Andreozzi F, Mannino GC, Perticone M, Perticone F, Sesti G. Elevated 1-h post-load plasma glucose levels in subjects with normal glucose tolerance are associated with a pro-atherogenic lipid profile. Atherosclerosis 2017; 256:15-20. [DOI: 10.1016/j.atherosclerosis.2016.11.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2016] [Revised: 10/25/2016] [Accepted: 11/16/2016] [Indexed: 12/11/2022]
|
|
40
|
Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ 2016; 355:i5953. [PMID: 27881363 PMCID: PMC5121106 DOI: 10.1136/bmj.i5953] [Citation(s) in RCA: 624] [Impact Index Per Article: 69.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/21/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality. DESIGN Meta-analysis of prospective cohort studies. DATA SOURCES Electronic databases (PubMed, Embase, and Google Scholar). SELECTION CRITERIA Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes. REVIEW METHODS Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals. RESULTS 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality. CONCLUSIONS Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.
Collapse
Affiliation(s)
- Yuli Huang
- Department of Cardiology, First People's Hospital of Shunde (Affiliated Hospital at Shunde, Southern Medical University), Foshan, 528300, China
| | - Xiaoyan Cai
- Clinical Medicine Research Centre, First People's Hospital of Shunde (Affiliated Hospital at Shunde, Southern Medical University), Foshan, China
| | - Weiyi Mai
- Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Meijun Li
- Department of Cardiology, First People's Hospital of Shunde (Affiliated Hospital at Shunde, Southern Medical University), Foshan, 528300, China
- Department of Cardiology, Graduate College, Guangdong medical university, Zhanjiang, China
| | - Yunzhao Hu
- Department of Cardiology, First People's Hospital of Shunde (Affiliated Hospital at Shunde, Southern Medical University), Foshan, 528300, China
| |
Collapse
|
|
41
|
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations. Circulation 2016; 133:2459-502. [PMID: 27297342 PMCID: PMC4910510 DOI: 10.1161/circulationaha.116.022194] [Citation(s) in RCA: 737] [Impact Index Per Article: 81.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.
Collapse
Affiliation(s)
- Cecilia C Low Wang
- From Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado School of Medicine, Aurora (C.C.L.); CPC Clinical Research, Aurora, CO (C.C.L., C.N.H., W.R.H.); Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora (C.N.H., W.R.H.); Joslin Diabetes Center, and Harvard Medical School, Boston, MA (A.B.G.)
| | - Connie N Hess
- From Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado School of Medicine, Aurora (C.C.L.); CPC Clinical Research, Aurora, CO (C.C.L., C.N.H., W.R.H.); Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora (C.N.H., W.R.H.); Joslin Diabetes Center, and Harvard Medical School, Boston, MA (A.B.G.)
| | - William R Hiatt
- From Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado School of Medicine, Aurora (C.C.L.); CPC Clinical Research, Aurora, CO (C.C.L., C.N.H., W.R.H.); Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora (C.N.H., W.R.H.); Joslin Diabetes Center, and Harvard Medical School, Boston, MA (A.B.G.)
| | - Allison B Goldfine
- From Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado School of Medicine, Aurora (C.C.L.); CPC Clinical Research, Aurora, CO (C.C.L., C.N.H., W.R.H.); Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora (C.N.H., W.R.H.); Joslin Diabetes Center, and Harvard Medical School, Boston, MA (A.B.G.).
| |
Collapse
|
|
42
|
Hanks LJ, Pelham JH, Vaid S, Casazza K, Ashraf AP. Overweight adolescents with type 2 diabetes have significantly higher lipoprotein abnormalities than those with type 1 diabetes. Diabetes Res Clin Pract 2016; 115:83-9. [PMID: 27242127 PMCID: PMC5373667 DOI: 10.1016/j.diabres.2016.03.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 12/22/2015] [Accepted: 03/01/2016] [Indexed: 02/08/2023]
Abstract
AIM Diabetes-associated glucoregulatory derangements may precipitate atherogenesis in childhood and CVD risk, particularly with obesity. We aimed to delineate lipoprotein profile differences between children with type 1 and 2 diabetes who are overweight/obese. METHODS Data were obtained from electronic medical records of patients ≥85th BMI percentile with type 1 (n=159) and type 2 (n=77) diabetes, ages 12-19y. Group differences were evaluated by correlations and general linear modeling analysis, adjusting for BMI, HbA1c, and diabetes duration. RESULTS There were no group differences in TC, LDL, or non-HDL. Fewer subjects with type 1 diabetes had low HDL (17 vs. 30%; P<0.05). While no difference in HbA1c level was observed between groups, HbA1c was positively correlated with TC (P≤0.0001), LDL (P≤0.0001), non-HDL (P≤0.0001), ApoB100 (P≤0.0001), and LDL pattern B (P≤0.0001). In adjusted models, apoB100 (85.4 vs. 91.3mg/dl; P<0.05) and incidence of LDL pattern B (21 vs. 42%; P<0.01) were lower in subjects with type 1 diabetes. BMI was inversely correlated with HDL, HDL-2 and HDL-3 (all P≤0.0001). The correlation of BMI with HDL-2 and HDL-3 were attenuated when evaluating subjects by diabetes type. CONCLUSIONS Despite having no difference in absolute LDL levels, children with type 2 diabetes were more likely to have small, dense LDL particle pattern, higher apo B100 and lower total HDL, HDL-2, and HDL-3 fractions. Furthermore, poor glycemic control was associated with abnormal lipoprotein profiles in patients with both type 1 and 2 diabetes.
Collapse
Affiliation(s)
- Lynae J Hanks
- Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, Children's of Alabama, University of Alabama at Birmingham (UAB), CPPII M30, 1601 4th Ave S., Birmingham, AL 35233, United States
| | - James Heath Pelham
- UAB School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294-0113, United States
| | - Shalini Vaid
- UAB School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294-0113, United States
| | - Krista Casazza
- Department of Pediatrics/Division of General Pediatrics and Adolescent Medicine, CPP1 310, 1601 4th Ave S., Birmingham, AL 35233-1711, United States
| | - Ambika P Ashraf
- Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, Children's of Alabama, University of Alabama at Birmingham (UAB), CPPII M30, 1601 4th Ave S., Birmingham, AL 35233, United States.
| |
Collapse
|
|
43
|
Malin SK, Rynders CA, Weltman JY, Barrett EJ, Weltman A. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance. PLoS One 2016; 11:e0154063. [PMID: 27111219 PMCID: PMC4844153 DOI: 10.1371/journal.pone.0154063] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Accepted: 04/07/2016] [Indexed: 12/14/2022] Open
Abstract
Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes.
Collapse
Affiliation(s)
- Steven K Malin
- Department of Kinesiology, University of Virginia, Charlottesville, VA, United States of America
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, United States of America
- Exercise Physiology Core Laboratory, University of Virginia, Charlottesville, VA, United States of America
| | - Corey A Rynders
- Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America
| | - Judy Y Weltman
- Exercise Physiology Core Laboratory, University of Virginia, Charlottesville, VA, United States of America
| | - Eugene J Barrett
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, United States of America
| | - Arthur Weltman
- Department of Kinesiology, University of Virginia, Charlottesville, VA, United States of America
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, United States of America
- Exercise Physiology Core Laboratory, University of Virginia, Charlottesville, VA, United States of America
| |
Collapse
|
|
44
|
Quispe R, Martin SS, Jones SR. Triglycerides to high-density lipoprotein-cholesterol ratio, glycemic control and cardiovascular risk in obese patients with type 2 diabetes. Curr Opin Endocrinol Diabetes Obes 2016; 23:150-6. [PMID: 26863278 DOI: 10.1097/med.0000000000000241] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW This article provides an update on the role of the triglyceride to high-density lipoprotein-cholesterol (triglyceride/HDL-C) ratio in the setting of obesity-related insulin resistance and type 2 diabetes mellitus. RECENT FINDINGS Insulin resistance and type 2 diabetes mellitus are well-established risk factors for cardiovascular diseases, and are commonly associated with metabolic abnormalities such as hypertriglyceridemia, low HDL-C and presence of small, dense low-dense lipoprotein (LDL) particles. Mounting evidence suggests that the triglyceride/HDL-C ratio is a marker of insulin resistance, although this relationship might vary as a function of ethnicity and sex. The triglyceride/HDL-C ratio has also been shown to correlate with other atherogenic lipid measurements, such as triglyceride-rich lipoproteins, remnant cholesterol and small dense LDL particles. Recent epidemiologic studies have shown that the triglyceride/HDL-C ratio associates with cardiovascular risk, mainly because of its association with insulin resistance. Finally, triglyceride/HDL-C can also be a marker of glycemic control, especially in obese patients with type 2 diabetes mellitus. SUMMARY The triglyceride/HDL-C integrates information on triglyceride-rich lipoproteins, insulin resistance and glycemic control. Future studies may better define its specific clinical role.
Collapse
Affiliation(s)
- Renato Quispe
- aJohns Hopkins Ciccarone Center for the Prevention of Heart Disease bWelch Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | | |
Collapse
|
|
45
|
Abstract
The interrelation between glucose and lipid metabolism is complex and comprises many aspects. In this context diabetic dyslipidemia is of utmost importance as it represents the crucial link between diabetes and cardiovascular disease. Although hypertriglyceridemia is usually the most prominent lipid abnormality in diabetic patients, reduction of low-density lipoprotein (LDL) cholesterol is the most important strategy to prevent cardiovascular disease. Statin trials and more recently the combination of statin with ezetimibe clearly showed that diabetic patients benefit from low LDL cholesterol levels. In this context the newly developed proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are of great interest as they reduce LDL cholesterol by 50-70 % independent of co-medication and largely independent of the underlying dyslipidemia. Subgroup analyses of phase 2 and phase 3 studies indicated that diabetic patients show a similar response to PCSK9 inhibitors as non-diabetic patients. Furthermore, the overall very low rate of side effects seems to be comparable between diabetic and non-diabetic patients. In contrast to statins PCSK9 inhibitors do not lead to an increased rate of new onset diabetes. Although data from safety studies (post hoc analyses) are very promising concerning the prevention of cardiovascular events, data from outcome studies will only become available in 2016. Until then PCSK9 inhibitors should be restricted to patients with very high risk and a significant distance from the LDL cholesterol target values (despite maximum possible lipid-lowering therapy with statins and ezetimibe). This approach will most likely have to be adapted when outcome data are available.
Collapse
|
|
46
|
Jiang ZG, de Boer IH, Mackey RH, Jensen MK, Lai M, Robson SC, Tracy R, Kuller LH, Mukamal KJ. Associations of insulin resistance, inflammation and liver synthetic function with very low-density lipoprotein: The Cardiovascular Health Study. Metabolism 2016; 65:92-9. [PMID: 26892520 PMCID: PMC4761104 DOI: 10.1016/j.metabol.2015.10.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 10/04/2015] [Accepted: 10/07/2015] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation. METHODS We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study. RESULTS Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size. CONCLUSION Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production.
Collapse
Affiliation(s)
- Z Gordon Jiang
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115.
| | - Ian H de Boer
- Division of Nephrology, University of Washington, Seattle, WA 98195
| | - Rachel H Mackey
- Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405
| | - Majken K Jensen
- Department of Nutrition, Harvard School of Public Health, Boston, MA 02115
| | - Michelle Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115
| | - Simon C Robson
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115
| | - Russell Tracy
- Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT 05405
| | - Lewis H Kuller
- Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261
| | - Kenneth J Mukamal
- Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA 02115
| |
Collapse
|
|
47
|
Aoyama-Sasabe S, Fukushima M, Xin X, Taniguchi A, Nakai Y, Mitsui R, Takahashi Y, Tsuji H, Yabe D, Yasuda K, Kurose T, Inagaki N, Seino Y. Insulin Secretory Defect and Insulin Resistance in Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance. J Diabetes Res 2016; 2016:1298601. [PMID: 26788515 PMCID: PMC4693016 DOI: 10.1155/2016/1298601] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Accepted: 08/18/2015] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVE To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. METHODS We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. RESULTS In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = -0.245, p < 0.0001) and had the strongest correlation with 2 h PG (β = -0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = -0.162, p < 0.0001) and had the strongest correlation with FPG (β = -0.214). CONCLUSIONS We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects.
Collapse
Affiliation(s)
- Sae Aoyama-Sasabe
- Division of Clinical Nutrition and Internal Medicine, Okayama Prefectural University, Okayama 719-1197, Japan
| | - Mitsuo Fukushima
- Division of Clinical Nutrition and Internal Medicine, Okayama Prefectural University, Okayama 719-1197, Japan
- Preemptive Medicine and Lifestyle-Related Disease Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan
- *Mitsuo Fukushima:
| | - Xin Xin
- Faculty of Computer Science and Systems Engineering, Okayama Prefectural University, Okayama 719-1197, Japan
| | - Ataru Taniguchi
- Division of Diabetes and Endocrinology, Kyoto Preventive Medical Center, Kyoto 604-8491, Japan
| | | | - Rie Mitsui
- Center for Preventive Medicine, St. Luke's International Hospital, Tokyo 104-6591, Japan
| | - Yoshitaka Takahashi
- Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama 719-1197, Japan
| | - Hideaki Tsuji
- Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama 719-1197, Japan
| | - Daisuke Yabe
- Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka 553-0003, Japan
- Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe 650-0047, Japan
| | - Koichiro Yasuda
- Department of Diabetes and Endocrinology, Saiseikai Noe Hospital, Osaka 536-0001, Japan
| | - Takeshi Kurose
- Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka 553-0003, Japan
- Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe 650-0047, Japan
| | - Nobuya Inagaki
- Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Yutaka Seino
- Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka 553-0003, Japan
- Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe 650-0047, Japan
| |
Collapse
|
|
48
|
de la Cuesta F, Mourino-Alvarez L, Baldan-Martin M, Moreno-Luna R, Barderas MG. Contribution of proteomics to the management of vascular disorders. TRANSLATIONAL PROTEOMICS 2015. [DOI: 10.1016/j.trprot.2014.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
|
|
49
|
Abstract
Diabetic dyslipidemia is characterized by elevated fasting and postprandial triglycerides, low HDL-cholesterol, elevated LDL-cholesterol and the predominance of small dense LDL particles. These lipid changes represent the major link between diabetes and the increased cardiovascular risk of diabetic patients. The underlying pathophysiology is only partially understood. Alterations of insulin sensitive pathways, increased concentrations of free fatty acids and low grade inflammation all play a role and result in an overproduction and decreased catabolism of triglyceride rich lipoproteins of intestinal and hepatic origin. The observed changes in HDL and LDL are mostly sequence to this. Lifestyle modification and glucose control may improve the lipid profile but statin therapy mediates the biggest benefit with respect to cardiovascular risk reduction. Therefore most diabetic patients should receive statin therapy. The role of other lipid lowering drugs, such as ezetimibe, fibrates, omega-3 fatty acids, niacin and bile acid sequestrants is less well defined as they are characterized by largely negative outcome trials. This review examines the pathophysiology of diabetic dyslipidemia and its relationship to cardiovascular diseases. Management approaches will also be discussed.
Collapse
|
|
50
|
Hamilton MT, Hamilton DG, Zderic TW. Sedentary behavior as a mediator of type 2 diabetes. MEDICINE AND SPORT SCIENCE 2014; 60:11-26. [PMID: 25226797 DOI: 10.1159/000357332] [Citation(s) in RCA: 111] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Over the past 5 years, the fastest growing new area of physical activity research centered around the concept that the large amount of time people spend sitting inactive may have significant physiological consequences hazardous to human health, including risk for type 2 diabetes and poor metabolism of lipids and glucose. Meta-analysis (10 studies) suggests there is a 112% greater relative risk associated with a large duration of sedentary behavior for type 2 diabetes. Meta-analysis also indicates significantly greater odds for metabolic syndrome. We also summarize results for 7 studies using objective measures of total sedentary time and focusing on cardiometabolic risks in persons at high risk for type 2 diabetes or already diagnosed with type 2 diabetes. The underlying hypothesis introduced in 2004 by the inactivity physiology paradigm has been that frequent and abundant contractile activity by certain types of skeletal muscle can have a potent influence on key physiological processes, even when the intensity is below that achieved through exercise. We explain some of the mechanisms for why the metabolism in slow-twitch oxidative skeletal muscle is key for understanding the healthy responses to low-intensity physical activity (LIPA). Findings from objective measures from inclinometry indicated that the quartile range for weekly sedentary time is ∼29 h/week. The total daily time that people sit, stand, and accumulate nonexercise steps is independent of traditionally recommended moderate-vigorous physical activity. The large amount of sedentary time associated with risk for disease can only be reduced significantly with safe and nonfatiguing LIPA, especially in the most at-risk proportion of the population. Importantly, experimental studies are starting to indicate that it will be especially insightful to understand the acute dose-response effects of LIPA in order to understand why reducing sedentary time can improve lipid and glucose metabolism for the prevention and treatment of chronic disorders related to type 2 diabetes.
Collapse
Affiliation(s)
- Marc T Hamilton
- Pennington Biomedical Research Center, Baton Rouge, La., USA
| | | | | |
Collapse
|