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Obrador de Hevia J, López-González ÁA, Ramírez-Manent JI, Paublini H, Tárraga López PJ, Martorell Sánchez C, Riutord-Sbert P. Association Between Alcohol Consumption, Other Healthy Habits and Sociodemographic Variables and the Values of Different Insulin Resistance Risk Scales in 139,634 Spanish Workers. Healthcare (Basel) 2025; 13:921. [PMID: 40281870 PMCID: PMC12026883 DOI: 10.3390/healthcare13080921] [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: 03/18/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Alcohol consumption is a major public health concern, influencing metabolic health and insulin resistance (IR). While moderate alcohol intake has been associated with potential metabolic benefits, excessive consumption is linked to IR and related disorders. This study examines the association between sociodemographic variables, health habits, and IR risk using validated metabolic indices. Methods: A dual-phase study was conducted, including a cross-sectional analysis of 139,634 Spanish workers and a retrospective longitudinal follow-up of 40,431 participants (2009-2019). Data on sociodemographic factors (age, sex and socioeconomic status) and health habits (smoking, alcohol consumption, diet and physical activity) were collected through standardized occupational health assessments. IR risk was assessed using the Triglyceride-Glucose Index (TyG), Metabolic Score for Insulin Resistance (METS-IR), and Single-Point Insulin Sensitivity Estimator (SPISE-IR). Binary logistic regression was used for statistical analysis. Results: Age, male sex, lower socioeconomic status, smoking, alcohol consumption, physical inactivity and low adherence to the Mediterranean diet were significantly associated with higher IR risk across all indices (p < 0.001). Alcohol consumption exhibited a dose-dependent relationship with IR, with excessive intake significantly increasing the risk of IR. Longitudinal data revealed a worsening IR profile over time, particularly among older, low-income and physically inactive individuals. Conclusions: Sociodemographic factors and lifestyle habits strongly influence IR. Preventive strategies focused on reducing alcohol consumption, smoking cessation and promoting physical activity and dietary improvements are essential to mitigate the risk of IR, especially in vulnerable populations. Further longitudinal studies are needed to establish causal relationships and refine intervention strategies.
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Affiliation(s)
- Joan Obrador de Hevia
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
| | - Ángel Arturo López-González
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
- Balearic Islands Health Service, 07003 Palma, Spain
- Balearic Islands Health Research Institute Foundation (IDISBA), 07004 Palma, Spain
| | - José Ignacio Ramírez-Manent
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Balearic Islands Health Service, 07003 Palma, Spain
- Balearic Islands Health Research Institute Foundation (IDISBA), 07004 Palma, Spain
- Faculty of Medicine, University of the Balearic Islands, 07122 Palma, Spain
| | - Hernán Paublini
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
| | | | - Cristina Martorell Sánchez
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
| | - Pere Riutord-Sbert
- ADEMA-Health Group, University Institute of Health Sciences (IUNICS), 07120 Palma, Spain; (J.O.d.H.); (J.I.R.-M.); (H.P.); (C.M.S.); (P.R.-S.)
- Faculty of Dentistry, ADEMA-UIB University School, 07009 Palma, Spain
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2
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Datta D, Kundu R, Basu R, Chakrabarti P. Pathophysiological hallmarks in type 2 diabetes heterogeneity (review). Diabetol Int 2025; 16:201-222. [PMID: 40166449 PMCID: PMC11954762 DOI: 10.1007/s13340-024-00783-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: 03/01/2024] [Accepted: 10/21/2024] [Indexed: 01/03/2025]
Abstract
The mechanistic complexity in type 2 diabetes (T2DM) is primarily responsible for the degrees of heterogeneity and development of complications. A complex mode of interactions between different pathophysiological events and diabetogenic environmental factors support for the genesis of diabetes heterogeneity both in phenotypic and clinical contexts. The currently used diabetes classification strategies suffer from several inconsistencies that cannot fully capture the inherent heterogeneity among the diabetes patients. To effectively address this pathobiological and heterogeneity-related issue in diabetes research, the current review proposes nine pathophysiological hallmarks of T2DM that aims to mechanistically explain complexities of diabetes associated pathophysiological events and their underlying features. These pathophysiological hallmarks are pancreatic beta cell dysfunction, insulin sensitivity, insulin resistance, obesity, aging, subclinical inflammation, metabolic dysregulation, prothrombotic state induction and hypertension. Detail knowledge of these pathophysiological hallmarks with their key molecular mediators, influencing factors, clinical biomarkers and clinical assessment methodologies will greatly support precision medicine approaches in diabetes including patient stratification, subtype diagnosis and treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-024-00783-w.
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Affiliation(s)
- Dipamoy Datta
- Computer Education Training Program, NICS Computer, Kolkata, 700032 India
- Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata, 700032 India
| | - Raja Kundu
- Computer Education Training Program, NICS Computer, Kolkata, 700032 India
| | - Rajdeep Basu
- Department of Endocrinology, Nil Ratan Sarkar Medical College, Kolkata, 700014 India
| | - Partha Chakrabarti
- Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata, 700032 India
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3
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Capoccia D, Leonetti F, Natali A, Tricò D, Perrini S, Sbraccia P, Guglielmi V. Remission of type 2 diabetes: position statement of the Italian society of diabetes (SID). Acta Diabetol 2024; 61:1309-1326. [PMID: 38942960 PMCID: PMC11486812 DOI: 10.1007/s00592-024-02317-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 05/31/2024] [Indexed: 06/30/2024]
Abstract
The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy balance. Any form of weight loss dramatically affects the natural history of T2D, favoring prevention, treatment, and even remission in the case of significant weight loss. However, weight regain, which is often accompanied by the recurrence or worsening of obesity complications such as T2D, is an inevitable biological phenomenon that is an integral part of the pathophysiology of obesity. This can occur not only after weight loss, but also during obesity treatment if it is not effective enough to counteract the physiological responses aimed at restoring adiposity to its pre-weight-loss equilibrium state. Over the past few years, many controlled and randomized studies have suggested a superior efficacy of bariatric surgery compared to conventional therapy in terms of weight loss, glycemic control, and rates of T2D remission. Recently, the therapeutic armamentarium in the field of diabetology has been enriched with new antihyperglycemic drugs with considerable efficacy in reducing body weight, which could play a pathogenetic role in the remission of T2D, not through the classical incretin effect, but by improving adipose tissue functions. All these concepts are discussed in this position statement, which aims to deepen the pathogenetic links between obesity and T2D, shift the paradigm from a "simple" interaction between insulin resistance and insulin deficiency, and evaluate the efficacy of different therapeutic interventions to improve T2D management and induce diabetes remission whenever still possible.
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Affiliation(s)
- Danila Capoccia
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Frida Leonetti
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Andrea Natali
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Domenico Tricò
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Sebastio Perrini
- Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy
| | - Paolo Sbraccia
- Department of Systems Medicine, Unit of Internal Medicine - Obesity Center, Policlinico Tor Vergata, University of Rome Tor Vergata, Rome, Italy
| | - Valeria Guglielmi
- Department of Systems Medicine, Unit of Internal Medicine - Obesity Center, Policlinico Tor Vergata, University of Rome Tor Vergata, Rome, Italy
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4
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Bahadoran Z, Mirmiran P, Ghasemi A. Adipose organ dysfunction and type 2 diabetes: Role of nitric oxide. Biochem Pharmacol 2024; 221:116043. [PMID: 38325496 DOI: 10.1016/j.bcp.2024.116043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/07/2024] [Accepted: 02/01/2024] [Indexed: 02/09/2024]
Abstract
Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NO·) in AT (dys)function in relation to developing T2D. The key aspects determining lipid and glucose homeostasis in AT depend on the physiological levels of the NO· produced via endothelial NO· synthases (eNOS). In addition to decreased NO· bioavailability (via decreased expression/activity of eNOS or scavenging NO·), excessive NO· produced by inducible NOS (iNOS) in response to hypoxia and AT inflammation may be a critical interfering factor diverting NO· signaling to the formation of reactive oxygen and nitrogen species, resulting in AT and whole-body metabolic dysfunction. Pharmacological approaches boosting AT-NO· availability at physiological levels (by increasing NO· production and its stability), as well as suppression of iNOS-NO· synthesis, are potential candidates for developing NO·-based therapeutics in T2D.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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5
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Zahra S, Zaib S, Khan I. Identification of isobenzofuranone derivatives as promising antidiabetic agents: Synthesis, in vitro and in vivo inhibition of α-glucosidase and α-amylase, computational docking analysis and molecular dynamics simulations. Int J Biol Macromol 2024; 259:129241. [PMID: 38199537 DOI: 10.1016/j.ijbiomac.2024.129241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/23/2023] [Accepted: 01/03/2024] [Indexed: 01/12/2024]
Abstract
Diabetes mellitus, one of the major health challenges of the 21st century, is associated with numerous biomedical complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases and liver disorders. To control the chronic hyperglycemic condition, the development of potential inhibitors of drug targets such as α-glucosidase and α-amylase remains a promising strategy and focus of continuous efforts. Therefore, in the present work, a concise library of isobenzofuranone derivatives (3a-q) was designed and synthesized using Suzuki-Miyaura cross-coupling approach. The biological potential of these heterocyclic compounds against carbohydrate-hydrolyzing enzymes; α-glucosidase and α-amylase, was examined. In vitro inhibitory results demonstrated that the tested isobenzofuranones were considerably more effective and potent inhibitors than the standard drug, acarbose. Compound 3d having an IC50 value of 6.82 ± 0.02 μM was emerged as the lead candidate against α-glucosidase with ⁓127-folds strong inhibition than acarbose. Similarly, compound 3g demonstrated ⁓11-folds higher inhibition strength against α-amylase when compared with acarbose. Both compounds were tested in vivo and results demonstrate that the treatment of diabetic rats with α-amylase inhibitor show more pronounced histopathological normalization in kidney and liver than with α-glucosidase inhibitor. The Lineweaver-Burk plot revealed an uncompetitive mode of inhibition for 3d against α-glucosidase whereas compound 3g exhibited mixed inhibition against α-amylase. Furthermore, in silico molecular docking and dynamics simulations validated the in vitro data for these compounds whereas pharmacokinetics profile revealed the druglike properties of potent inhibitors.
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Affiliation(s)
- Shabab Zahra
- Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore 54590, Pakistan
| | - Sumera Zaib
- Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore 54590, Pakistan.
| | - Imtiaz Khan
- Department of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
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6
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Klein T, Augustin R, Hennige AM. Perspectives in weight control in diabetes - Survodutide. Diabetes Res Clin Pract 2024; 207:110779. [PMID: 37330144 DOI: 10.1016/j.diabres.2023.110779] [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: 04/14/2023] [Revised: 06/09/2023] [Accepted: 06/11/2023] [Indexed: 06/19/2023]
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved treatments for Type 2 diabetes mellitus, with liraglutide and semaglutide also approved for the treatment of obesity. The natural gut hormone oxyntomodulin is a weak dual agonist of the glucagon receptor (GCGR) and GLP-1R. Development of poly-agonists mimicking oxyntomodulin, such as the novel dual GCGR/GLP-1R agonist survodutide, represents an important step towards a more effective treatment for people with Type 2 diabetes mellitus and obesity. Survodutide is a 29-amino acid peptide derived from glucagon, with the incorporation of potent GLP-1 activities. It contains a C18 diacid which mediates binding to albumin, thereby prolonging the half-life to enable once-weekly subcutaneous dosing. The utilisation of GCGR agonism aims to enhance body weight-lowering effects by increasing energy expenditure in addition to the anorectic action of GLP-1R agonists. Glucose-lowering efficacy of survodutide has been demonstrated in a Phase II trial in patients with Type 2 diabetes mellitus and obesity and was associated with clinically meaningful body weight loss. These data highlight the potential of dual GCGR/GLP-1R agonism for reducing glycated haemoglobin and body weight in patients with Type 2 diabetes mellitus, and for greater therapeutic efficacy compared with GLP-1R agonism alone.
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Affiliation(s)
- Thomas Klein
- Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany
| | - Robert Augustin
- Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany
| | - Anita M Hennige
- Boehringer Ingelheim International GmbH, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
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7
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Alam A, Dhoundiyal S, Ahmad N, Rao GSNK. Unveiling Diabetes: Categories, Genetics, Diagnostics, Treatments, and Future Horizons. Curr Diabetes Rev 2024; 20:e180823219972. [PMID: 37594107 DOI: 10.2174/1573399820666230818092958] [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: 03/19/2023] [Revised: 06/15/2023] [Accepted: 07/06/2023] [Indexed: 08/19/2023]
Abstract
Diabetes mellitus is a global epidemic affecting millions of individuals worldwide. This comprehensive review aims to provide a thorough understanding of the categorization, disease identity, genetic architecture, diagnosis, and treatment of diabetes. The categorization of diabetes is discussed, with a focus on type 1 and type 2 diabetes, as well as the lesser-known types, type 3 and type 4 diabetes. The geographical variation, age, gender, and ethnic differences in the prevalence of type 1 and type 2 diabetes are explored. The impact of disease identity on disease management and the role of autoimmunity in diabetes are examined. The genetic architecture of diabetes, including the interplay between genotype and phenotype, is discussed to enhance our understanding of the underlying mechanisms. The importance of insulin injection sites and the insulin signalling pathway in diabetes management are highlighted. The diagnostic techniques for diabetes are reviewed, along with advancements for improved differentiation between types. Treatment and management approaches, including medications used in diabetes management are presented. Finally, future perspectives are discussed, emphasizing the need for further research and interventions to address the global burden of diabetes. This review serves as a valuable resource for healthcare professionals, researchers, and policymakers, providing insights to develop targeted strategies for the prevention, diagnosis, and management of this complex disease.
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Affiliation(s)
- Aftab Alam
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Shivang Dhoundiyal
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Niyaz Ahmad
- Department of Pharmaceutical Analysis, Green Research Lab, Green Industrial Company, Second Industrial Area, Riyadh 14334, Saudi Arabia
| | - G S N Koteswara Rao
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India
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Ye J, Li Y, Wang X, Yu M, Liu X, Zhang H, Meng Q, Majeed U, Jian L, Song W, Xue W, Luo Y, Yue T. Positive interactions among Corynebacterium glutamicum and keystone bacteria producing SCFAs benefited T2D mice to rebuild gut eubiosis. Food Res Int 2023; 172:113163. [PMID: 37689914 DOI: 10.1016/j.foodres.2023.113163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/14/2023] [Accepted: 06/16/2023] [Indexed: 09/11/2023]
Abstract
Accumulating evidences strongly support the correlations between the compositions of gut microbiome and therapeutic effects on Type 2 diabetes (T2D). Notably, gut microbes such as Akkermansia muciniphila are found able to regulate microecological balance and alleviate dysmetabolism of mice bearing T2D. In order to search out similarly functional bacteria, bacteriophage MS2 with a good specificity to bacteria carrying fertility (F) factor were used to treat T2D mice. Based on multi-omics analysis of microbiome and global metabolism of mice, we observed that gavage of bacteriophage MS2 and metformin led to a significant increase in the abundance of Corynebacterium glutamicum and A. muciniphila, respectively. Consequently, the gut microbiota were remodeled, leading to variations in metabolites and a substantial increase in short-chain fatty acids (SCFAs). In which, the amount of acetate, propionate, and butyrate presented negative correlations to that of proinflammatory cytokines, which was beneficial to repairing the intestinal barriers and improving their functions. Moreover, main short fatty acid (SCFA) producers exhibited positive interactions, further facilitating the restoration of gut eubiosis. These findings revealed that C. glutamicum and its metabolites may be potential dietary supplements for the treatment of T2D. Moreover, our research contributes to a novel understanding of the underlying mechanism by which functional foods exert their anti-diabetic effects.
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Affiliation(s)
- Jianming Ye
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Yihua Li
- The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Xiaochen Wang
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Mengxi Yu
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Xuehua Liu
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Huaxin Zhang
- College of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China
| | - Qiang Meng
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Usman Majeed
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Lijuan Jian
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Wei Song
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China
| | - Weiming Xue
- College of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China
| | - Yane Luo
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China; Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Shaanxi Xi'an 710069, China; Research Center of Food Safety Risk Assessment and Control, Shaanxi, Xi'an 710069, China.
| | - Tianli Yue
- College of Food Science and Technology, Northwest University, Xi'an, Shaanxi 710069, China; Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Shaanxi Xi'an 710069, China; Research Center of Food Safety Risk Assessment and Control, Shaanxi, Xi'an 710069, China.
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9
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Atella V, Belotti F, Cricelli C, Giaccherini M, Medea G, Nicolucci A, Piano Mortari A, Sbraccia P. Outpatient healthcare costs associated with overweight and obesity in Italy. BMC Health Serv Res 2023; 23:619. [PMID: 37308927 PMCID: PMC10258973 DOI: 10.1186/s12913-023-09576-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 05/18/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations. METHODS The study is based on a representative national sample of adults, with data obtained from electronic clinical records of 900 Italian general practitioners. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2, and 3) and glucose metabolism status (normoglycemia - NGT; impaired fasting glucose - IFG; diabetes mellitus - DM). Outpatient health expenditures include diagnostic tests, specialist visits, and drugs. RESULTS Data relative to 991,917 adults were analyzed. Annual per capita expenditure rose from 252.2 Euro among individuals with normal weight to 752.9 Euro among those with class 3 obesity. The presence of obesity determined an excess cost, particularly among younger individuals. Within each BMI class, the presence of IFG or DM2 identified subgroups of individuals with substantially higher healthcare expenditures. CONCLUSIONS Outpatient healthcare costs markedly increased with increasing BMI in all age categories, particularly among individuals below 65. Addressing the double burden of excess weight and hyperglycemia represents a significant challenge and a healthcare priority.
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Affiliation(s)
- Vincenzo Atella
- Department of Economics and Finance, University of Rome Tor Vergata, via Columbia n. 2, 00133, Roma, Italy.
- CEIS Tor Vergata, University of Rome Tor Vergata, Roma, Italy.
| | - Federico Belotti
- Department of Economics and Finance, University of Rome Tor Vergata, via Columbia n. 2, 00133, Roma, Italy
- CEIS Tor Vergata, University of Rome Tor Vergata, Roma, Italy
| | | | | | - Gerardo Medea
- Italian College of General Practitioners, Florence, Italy
| | - Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology - CORESEARCH, Pescara, Italy
| | - Andrea Piano Mortari
- Department of Economics and Finance, University of Rome Tor Vergata, via Columbia n. 2, 00133, Roma, Italy
- CEIS Tor Vergata, University of Rome Tor Vergata, Roma, Italy
- Department of Programming, Ministry of Health, Roma, Italy
| | - Paolo Sbraccia
- Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy
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Vidmar AP, Durazo-Arvizu R, Weigensberg MJ, Alderete TL, Goran MI. Rapid Decline in β-Cell Function and Increasing Adiposity Are Associated With Conversion to Type 2 Diabetes in At-Risk Latino Youth. Diabetes 2023; 72:735-745. [PMID: 36972018 PMCID: PMC10202769 DOI: 10.2337/db22-1034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 03/22/2023] [Indexed: 04/16/2023]
Abstract
Youth-onset type 2 diabetes (T2D) is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Here, we describe findings from a longitudinal cohort study in 262 Latino children with overweight/obesity at risk of developing T2D with annual measures of oral and intravenous glucose tolerance (IVGTT), body composition, and fat distribution. Logistic binomial regression was used to identify significant predictors in those who developed T2D compared with matched control participants, and mixed-effects growth models were used to compare rates of change in metabolic versus adiposity measures between groups. Overall conversion rate to T2D at year 5 was 2% (n = 6). Rate of decline in disposition index (DI), measured with an IVGTT, over 5 years was three times higher in case patients (-341.7 units per year) compared with the extended cohort (-106.7 units per year) and 20 times higher compared with control participants (-15.2 units per year). Case patients had significantly higher annual increases in fasting glucose, hemoglobin A1c (HbA1c), waist circumference, and trunk fat, and there was an inverse correlation between rate of decline in DI and rates of increase in adiposity measures. T2D development in at-risk Latino youth is associated with a substantial and rapid decrease in DI that is directly correlated with increases in fasting glucose, HbA1c, and adiposity. ARTICLE HIGHLIGHTS Youth-onset type 2 diabetes is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Overall conversion rate to type 2 diabetes over 5 years was 2%. In youth who converted to type 2 diabetes, disposition index decreased rapidly by 85% compared with that in patients who did not convert during the study period. There was an inverse correlation between rate of decline in disposition index and rates of increase in various adiposity measures.
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Affiliation(s)
- Alaina P. Vidmar
- Division of Endocrinology, Department of Pediatrics, Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
- Department of Pediatrics, Keck School of Medicine, Los Angeles, CA
| | - Ramon Durazo-Arvizu
- Southern California Clinical and Translational Science Institute Biostatistics Core, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Marc J. Weigensberg
- Department of Pediatrics, University of Southern California, Los Angeles, CA
| | - Tanya L. Alderete
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO
| | - Michael I. Goran
- Division of Endocrinology, Department of Pediatrics, Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA
- Department of Pediatrics, Keck School of Medicine, Los Angeles, CA
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11
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Guglielmi V, Bettini S, Sbraccia P, Busetto L, Pellegrini M, Yumuk V, Colao AM, El Ghoch M, Muscogiuri G. Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications. Curr Obes Rep 2023; 12:127-146. [PMID: 37209215 PMCID: PMC10250472 DOI: 10.1007/s13679-023-00502-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/29/2023] [Indexed: 05/22/2023]
Abstract
PURPOSE OF REVIEW To highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity. RECENT FINDINGS Obesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.
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Affiliation(s)
- Valeria Guglielmi
- Dept. of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Internal Medicine Unit - Obesity Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Silvia Bettini
- Center for the Study and the Integrated Treatment of Obesity, Internal Medicine 3, Padua University Hospital, Padua, Italy
| | - Paolo Sbraccia
- Dept. of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Internal Medicine Unit - Obesity Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Luca Busetto
- Center for the Study and the Integrated Treatment of Obesity, Internal Medicine 3, Padua University Hospital, Padua, Italy
| | - Massimo Pellegrini
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Volkan Yumuk
- Division of Endocrinology, Metabolism & Diabetes Istanbul University Cerrahpaşa Medical Faculty, Istanbul, Türkiye
| | - Anna Maria Colao
- Italian Centre for the Care and Well-Being of Patients With Obesity (C.I.B.O), Dipartimento Di Medicina Clinica E Chirurgia, Università Federico II, 80131 Naples, Italy
- Dipartimento Di Medicina Clinica E Chirurgia, Diabetologia E Andrologia, Unità Di Endocrinologia, Università Degli Studi Di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy
- Cattedra Unesco ”Educazione Alla Salute E Allo Sviluppo Sostenibile”, University Federico II, Naples, Italy
| | - Marwan El Ghoch
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Beirut Arab University, P.O. Box 11-5020, Riad El Solh, Beirut, Lebanon
| | - Giovanna Muscogiuri
- Dipartimento Di Medicina Clinica E Chirurgia, Diabetologia E Andrologia, Unità Di Endocrinologia, Università Degli Studi Di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy
- Cattedra Unesco ”Educazione Alla Salute E Allo Sviluppo Sostenibile”, University Federico II, Naples, Italy
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12
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Zou X, Chen M, Sun L, Tan Q. Hyperinsulinemia Impaired Coronary Collateral Circulation in Patients with Chronic Total Coronary Occlusion. Diabetes Metab Syndr Obes 2023; 16:1425-1433. [PMID: 37223493 PMCID: PMC10202109 DOI: 10.2147/dmso.s402849] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/16/2023] [Indexed: 05/25/2023] Open
Abstract
Background and Objectives Hyperinsulinemia impaired cardiovascular system and endothelial function in the population. The purpose of this study was to explore the relationship between hyperinsulinemia and coronary collateral circulation in patients with chronic total coronary occlusion. Methods Patients with stable angina and at least one total coronary occlusion were enrolled in this study. Collateral grade was determined according to Rentrop's classification. Patients were divided into a good coronary collateral circulation (CCC) group (grade 2 or 3 collateral vessels, n = 223) and a poor CCC group (grade 0 or 1 collateral vessels, n = 115). Fasting insulin level (FINS) and fasting glucose level (FBS) were measured. Endothelial function evaluated by flow-mediated dilation (FMD). Results Serum FINS level was significantly increased in the poor CCC group (P < 0.01). Patients in the poor CCC group had higher levels of FBS, HbA1C, and homeostasis model assessment for insulin resistance (HOMA-IR) than patients in the good CCC group. The poor CCC group also had lower levels of FMD, lower LVEF and higher syntax scores than the good CCC group. Hyperinsulinemia (T3, FINS ≥15.22 μIU/mL) increased OR for the incidence of the poor CCC group (OR 2.419, 95% CI 1.780-3.287) in multivariate analysis. Multivariate logistic regression also revealed that diabetes, HbA1c, HOMA-IR, HDL-C and Syntax score were independent predictors of poor CCC (all P < 0.05). Conclusion Hyperinsulinemia is a valuable predictor of poor collateral formation in patients with chronic total coronary occlusion.
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Affiliation(s)
- Xiaoyi Zou
- Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of China
| | - Ming Chen
- Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of China
| | - Limin Sun
- Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of China
| | - Qiang Tan
- Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of China
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13
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Colangeli L, Escobar Marcillo DI, Simonelli V, Iorio E, Rinaldi T, Sbraccia P, Fortini P, Guglielmi V. The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity. Nutrients 2023; 15:nu15071723. [PMID: 37049562 PMCID: PMC10097238 DOI: 10.3390/nu15071723] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/19/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.
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14
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Barre DE, Mizier-Barre KA, Griscti O, Hafez K. Fatty acid correlations with HOMA-IR and HOMA-% β are differentially dictated by their serum free and total pools and flaxseed oil supplementation. Endocr Regul 2023; 57:18-24. [PMID: 36753666 DOI: 10.2478/enr-2023-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
Abstract
Objective. The intent of the present study was to test two hypotheses. The primary hypothesis was that there would be differences between blood serum individual free fatty acids (SIFFA) and serum individual total fatty acids (SITFA) in terms of their different relationships (correlations) to each of homeostatic model assessment-individual insulin resistance (HOMA-IR) and homeostatic model assessment-individual insulin resistance-percentage β-cell function (HOMA-% β) remaining in human type 2 diabetic patients with pre-flaxseed oil (FXO) and pre-safflower oil (SFO) administration. The secondary hypothesis was that FXO (rich in alpha-linolenic acid, ALA) supplementation would alter these correlations differently in the SIFFA and STIFFA pools in comparison with the placebo SFO (poor in ALA). Methods. Patients were recruited via a newspaper advertisement and two physicians. All patients came to visit 1 and three months later to visit 2. At visit 2, the subjects were randomly assigned (double-blind) to flaxseed or safflower oil (placebo) treatment for three months until visit 3. Results. There were pre-intervention differences in the SIFFA and STIFA pool's relationships with each of HOMA-IR and HOMA-% β. These relatioships remained either unchanged or became significant after intervention (treatment or placebo). There was a negative correlation found between HOMA-IR and serum free ALA (SFALA) mol % after FXO. Serum total ALA (STALA) mol % had no significant correlations with HOMA-IR and HOMA- % β before and after flaxseed oil administration. Conclusions. The SIFFA and SITFA pools have different relationships with HOMA-IR and HOMA-% β for each of pre- and post-intervention. It is concluded that the data support both the primary and the secondary hypotheses indicating that they are correct.
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Affiliation(s)
- Douglas E Barre
- Department of Health Sciences, Cape Breton University, Sydney, Nova Scotia, Canada
| | | | - Odette Griscti
- School of Nursing, Cape Breton University, Sydney, Nova Scotia, Canada
| | - Kevin Hafez
- Royal Commission for Riyadh City, Health Sector Planning & Development Advisor, Riyadh, Kingdom of Saudi Arabia
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15
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Calderón-DuPont D, Torre-Villalvazo I, Díaz-Villaseñor A. Is insulin resistance tissue-dependent and substrate-specific? The role of white adipose tissue and skeletal muscle. Biochimie 2023; 204:48-68. [PMID: 36099940 DOI: 10.1016/j.biochi.2022.08.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 08/19/2022] [Accepted: 08/31/2022] [Indexed: 01/12/2023]
Abstract
Insulin resistance (IR) refers to a reduction in the ability of insulin to exert its metabolic effects in organs such as adipose tissue (AT) and skeletal muscle (SM), leading to chronic diseases such as type 2 diabetes, hepatic steatosis, and cardiovascular diseases. Obesity is the main cause of IR, however not all subjects with obesity develop clinical insulin resistance, and not all clinically insulin-resistant people have obesity. Recent evidence implies that IR onset is tissue-dependent (AT or SM) and/or substrate-specific (glucometabolic or lipometabolic). Therefore, the aims of the present review are 1) to describe the glucometabolic and lipometabolic activities of insulin in AT and SM in the maintenance of whole-body metabolic homeostasis, 2) to discuss the pathophysiology of substrate-specific IR in AT and SM, and 3) to highlight novel validated tests to assess tissue and substrate-specific IR that are easy to perform in clinical practice. In AT, glucometabolic IR reduces glucose availability for glycerol and fatty acid synthesis, thus decreasing the esterification and synthesis of signaling bioactive lipids. Lipometabolic IR in AT impairs the antilipolytic effect of insulin and lipogenesis, leading to an increase in circulating FFAs and generating lipotoxicity in peripheral tissues. In SM, glucometabolic IR reduces glucose uptake, whereas lipometabolic IR impairs mitochondrial lipid oxidation, increasing oxidative stress and inflammation, all of which lead to metabolic inflexibility. Understanding tissue-dependent and substrate-specific IR is of paramount importance for early detection before clinical manifestations and for the development of more specific treatments or direct interventions to prevent chronic life-threatening diseases.
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Affiliation(s)
- Diana Calderón-DuPont
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico; Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico
| | - Ivan Torre-Villalvazo
- Departamento de Fisiología de la Nutrición, Instituto Nacional en Ciencias Médicas y Nutricíon Salvador Zubirán, Mexico City, 14000, Mexico
| | - Andrea Díaz-Villaseñor
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico.
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16
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Gong R, Liu Y, Luo G, Yin J, Xiao Z, Hu T. Using optimal subset regression to identify factors associated with insulin resistance and construct predictive models in the US adult population. Endocr Connect 2022; 11:EC-22-0066. [PMID: 35686717 PMCID: PMC9254325 DOI: 10.1530/ec-22-0066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 06/09/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND In recent decades, with the development of the global economy and the improvement of living standards, insulin resistance (IR) has become a common phenomenon. Current studies have shown that IR varies between races. Therefore, it is necessary to develop individual prediction models for each country. The purpose of this study was to develop a predictive model of IR applicable to the US population. METHOD In total, 11 cycles of data from the NHANES database were selected for this study. Of these, participants from 1999 to 2010 (n = 14931) were used to establish the model, and participants from 2011 to 2020 (n = 13,646) were used to validate the model. Univariate and multivariable logistic regression was used to analyze the factors associated with IR. Optimal subset regression was used to filter the best modeling variables. ROC curves, calibration curves, and decision curve analysis were used to determine the strengths and weaknesses of the model. RESULTS After screening the variables by optimal subset regression, variables with covariance were excluded, and a total of seven factors (including HDL, LDL, ALB, GLB, GLU, BMI, and waist) were finally included to establish the prediction model. The AUCs were 0.851 and 0.857 in the training and validation sets, respectively, and the Brier value of the calibration curve was 0.153. CONCLUSION The optimal subset predictive model proposed in this study has a great performance in predicting IR, and the decision curve analysis shows that it has a high net clinical benefit, which can help clinicians and epidemiologists easily detect IR and take appropriate interventions as early as possible.
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Affiliation(s)
- Rongpeng Gong
- Medical College of Qinghai University, Xining, People’s Republic of China
| | - Yuanyuan Liu
- Medical College of Qinghai University, Xining, People’s Republic of China
| | - Gang Luo
- Medical College of Qinghai University, Xining, People’s Republic of China
| | - Jiahui Yin
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zuomiao Xiao
- Department of Clinical Laboratory, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - Tianyang Hu
- Precision Medicine Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Correspondence should be addressed to T Hu:
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17
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Busetto L, Sbraccia P, Vettor R. Obesity management: at the forefront against disease stigma and therapeutic inertia. Eat Weight Disord 2022; 27:761-768. [PMID: 34052990 PMCID: PMC8933346 DOI: 10.1007/s40519-021-01217-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/17/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.
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Affiliation(s)
- Luca Busetto
- Department of Medicine, University of Padova, Padua, Italy.
- Clinica Medica 3, Azienda Ospedale-Università di Padova, Via Giustiniani 2, 35128, Padua, Italy.
| | - Paolo Sbraccia
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Roberto Vettor
- Department of Medicine, University of Padova, Padua, Italy
- Clinica Medica 3, Azienda Ospedale-Università di Padova, Via Giustiniani 2, 35128, Padua, Italy
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18
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Koga T, Peters JM. Targeting Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) for the Treatment or Prevention of Alcoholic Liver Disease. Biol Pharm Bull 2021; 44:1598-1606. [PMID: 34719638 DOI: 10.1248/bpb.b21-00486] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Excessive, chronic alcohol consumption can lead to alcoholic liver disease. The etiology of alcoholic liver disease is multifactorial and is influenced by alterations in gene expression and changes in fatty acid metabolism, oxidative stress, and insulin resistance. These events can lead to steatosis, fibrosis, and eventually to cirrhosis and liver cancer. Many of these functions are regulated by peroxisome proliferator-activated receptors (PPARs). Thus, it is not surprising that PPARs can modulate the mechanisms that cause alcoholic liver disease. While the roles of PPARα and PPARγ are clearer, the role of PPARβ/δ in alcoholic liver disease requires further clarification. This review summarizes the current understanding based on recent studies that indicate that PPARβ/δ can likely be targeted for the treatment and/or the prevention of alcoholic liver disease.
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Affiliation(s)
- Takayuki Koga
- Laboratory of Hygienic Chemistry, Department of Health Science and Hygiene, Daiichi University of Pharmacy
| | - Jeffrey M Peters
- Department of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University
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19
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Janssen JAMJL. Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer. Int J Mol Sci 2021; 22:ijms22157797. [PMID: 34360563 PMCID: PMC8345990 DOI: 10.3390/ijms22157797] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/11/2021] [Accepted: 07/13/2021] [Indexed: 01/10/2023] Open
Abstract
For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.
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Affiliation(s)
- Joseph A M J L Janssen
- Department of internal Medicine, Division of Endocrinology, Erasmus Medical Center, 40, 3015 GD Rotterdam, The Netherlands
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20
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Chi T, Lin J, Wang M, Zhao Y, Liao Z, Wei P. Non-Coding RNA as Biomarkers for Type 2 Diabetes Development and Clinical Management. Front Endocrinol (Lausanne) 2021; 12:630032. [PMID: 34603195 PMCID: PMC8484715 DOI: 10.3389/fendo.2021.630032] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 08/10/2021] [Indexed: 12/21/2022] Open
Abstract
Diabetes, a metabolic disease characterized by high blood glucose and other complications, has undefined causes and multiple risk factors, including inappropriate diet, unhealthy lifestyles, and genetic predisposition. The two most distinguished types of diabetes are type 1 and type 2 diabetes, resulting from the autoimmune impairment of insulin-generating pancreatic β cells and insulin insensitivity, respectively. Non-coding RNAs (ncRNAs), a cohort of RNAs with little transcriptional value, have been found to exert substantial importance in epigenetic and posttranscriptional modulation of gene expression such as messenger RNA (mRNA) silencing. This review mainly focuses on the pathology of type 2 diabetes (T2D) and ncRNAs as potential biomarkers in T2D development and clinical management. We consolidate the pathogenesis, diagnosis, and current treatments of T2D, and present the existing evidence on changes in multiple types of ncRNAs in response to various pathological changes and dysfunctions in different stages of T2D.
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Affiliation(s)
- Tiange Chi
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Jiaran Lin
- Department of Nephrology and Endocrinology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Mina Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Yihan Zhao
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden
- *Correspondence: Peng Wei, ; Zehuan Liao,
| | - Peng Wei
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Peng Wei, ; Zehuan Liao,
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