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      Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome

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          Abstract

          The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabolic risk factors including abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension, and low high-density lipoprotein cholesterol levels. These risk factors could dramatically increase the prevalence of type 2 diabetes and cardiovascular disease. The reported prevalence of the metabolic syndrome varies, greatly depending on the definition used, gender, age, socioeconomic status, and the ethnic background of study cohorts. Clinical and epidemiological studies have clearly demonstrated that the metabolic syndrome starts with central obesity. Because the prevalence of obesity has doubly increased worldwide over the past 30 years, the prevalence of the metabolic syndrome has markedly boosted in parallel. Therefore, obesity has been recognized as the leading cause for the metabolic syndrome since it is strongly associated with all metabolic risk factors. High prevalence of the metabolic syndrome is not unique to the USA and Europe and it is also increasing in most Asian countries. Insulin resistance has elucidated most, if not all, of the pathophysiology of the metabolic syndrome because it contributes to hyperglycemia. Furthermore, a major contributor to the development of insulin resistance is an overabundance of circulating fatty acids. Plasma fatty acids are derived mainly from the triglycerides stored in adipose tissues, which are released through the action of the cyclic AMP-dependent enzyme, hormone sensitive lipase. This review summarizes the latest concepts in the definition, pathogenesis, pathophysiology, and diagnosis of the metabolic syndrome, as well as its preventive measures and therapeutic strategies in children and adolescents.

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          Most cited references343

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          Banting lecture 1988. Role of insulin resistance in human disease.

          G M Reaven (1988)
          Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Physical Activity and Public Health: Updated Recommendation for Adults From the American College of Sports Medicine and the American Heart Association

            In 1995 the American College of Sports Medicine and the Centers for Disease Control and Prevention published national guidelines on Physical Activity and Public Health. The Committee on Exercise and Cardiac Rehabilitation of the American Heart Association endorsed and supported these recommendations. The purpose of the present report is to update and clarify the 1995 recommendations on the types and amounts of physical activity needed by healthy adults to improve and maintain health. Development of this document was by an expert panel of scientists, including physicians, epidemiologists, exercise scientists, and public health specialists. This panel reviewed advances in pertinent physiologic, epidemiologic, and clinical scientific data, including primary research articles and reviews published since the original recommendation was issued in 1995. Issues considered by the panel included new scientific evidence relating physical activity to health, physical activity recommendations by various organizations in the interim, and communications issues. Key points related to updating the physical activity recommendation were outlined and writing groups were formed. A draft manuscript was prepared and circulated for review to the expert panel as well as to outside experts. Comments were integrated into the final recommendation. To promote and maintain health, all healthy adults aged 18 to 65 yr need moderate-intensity aerobic (endurance) physical activity for a minimum of 30 min on five days each week or vigorous-intensity aerobic physical activity for a minimum of 20 min on three days each week. [I (A)] Combinations of moderate- and vigorous-intensity activity can be performed to meet this recommendation. [IIa (B)] For example, a person can meet the recommendation by walking briskly for 30 min twice during the week and then jogging for 20 min on two other days. Moderate-intensity aerobic activity, which is generally equivalent to a brisk walk and noticeably accelerates the heart rate, can be accumulated toward the 30-min minimum by performing bouts each lasting 10 or more minutes. [I (B)] Vigorous-intensity activity is exemplified by jogging, and causes rapid breathing and a substantial increase in heart rate. In addition, every adult should perform activities that maintain or increase muscular strength and endurance a minimum of two days each week. [IIa (A)] Because of the dose-response relation between physical activity and health, persons who wish to further improve their personal fitness, reduce their risk for chronic diseases and disabilities or prevent unhealthy weight gain may benefit by exceeding the minimum recommended amounts of physical activity. [I (A)]
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              Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies.

              The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies. Controversy exists regarding the cardiovascular risk associated with MetSyn. We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases. We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR 2.63 vs. 1.98, p = 0.09), in studies enrolling lower risk (<10%) individuals (RR 1.96 vs. 1.43, p = 0.04), and in studies using factor analysis or the World Health Organization definition (RR 2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p = 0.005). The association remained after adjusting for traditional cardiovascular risk factors (RR 1.54, 95% CI 1.32 to 1.79). The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions.
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                Author and article information

                Journal
                Pediatr Gastroenterol Hepatol Nutr
                Pediatr Gastroenterol Hepatol Nutr
                PGHN
                Pediatric Gastroenterology, Hepatology & Nutrition
                The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition
                2234-8646
                2234-8840
                May 2020
                08 May 2020
                : 23
                : 3
                : 189-230
                Affiliations
                [1 ]Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.
                [2 ]Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                [3 ]Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
                [4 ]Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy.
                Author notes
                Correspondence to David Q.-H. Wang. Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. david.wang@ 123456einsteinmed.org
                Author information
                https://orcid.org/0000-0002-9830-1236
                https://orcid.org/0000-0002-0048-9112
                https://orcid.org/0000-0003-2505-0218
                https://orcid.org/0000-0001-5359-1471
                https://orcid.org/0000-0002-5439-7651
                Article
                10.5223/pghn.2020.23.3.189
                7231748
                32483543
                0f7b98f2-1f06-4c77-909d-58364bace2ac
                Copyright © 2020 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 February 2020
                : 17 April 2020
                : 21 April 2020
                Funding
                Funded by: National Institutes of Health, CrossRef https://doi.org/10.13039/100000002;
                Award ID: DK106249
                Award ID: DK114516
                Award ID: P30 DK041296
                Categories
                Review Article

                obesity,diabetes,insulin resistance,dyslipidemia,hyperglycemia

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