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1.
The chemical exposome of type 2 diabetes mellitus: Opportunities and challenges in the omics era.
Misra, BB, Misra, A
Diabetes & metabolic syndrome. 2020;(1):23-38
Abstract
Type 2 diabetes mellitus (T2DM) is a global silent killer, with > 450 million affected adults worldwide. A diverse array of non-modifiable risk factors such as family history, age (> 45 yrs), race/ethnicity, genetics, and history of gestational diabetes and modifiable risk factors such as physical inactivity, high body fat, body weight, high blood pressure, and high cholesterol for progression of prediabetes to T2DM. Given, that the modern world human population is constantly exposed to multiple stressors in the form of physical (i.e., sound, weather etc.) and chemical environment (i.e., diet, pollutants etc.), industrialization, and modernization has led to form a basis for exposomal correlation with T2DM incidence. Over the past decade, there have been emerging reports on association of levels of persistent organic pollutants (POPs), phthalates, antibiotics, drugs, air pollution, pesticides, and heavy metals with T2DM. In this review, we discuss the well known chemical exposome that has been associated with T2DM; the tools and approaches to capture this chemical exposome, and future opportunities and challenges in this exciting area of research. We further provide a window of thoughts, whether omics technologies can help fill in the gaps to help provide high throughput exposomics datasets in an unbiased manner to help understand T2DM pathophysiology in the context of industrialization, drastic lifestyle changes, urbanization, and pollution. We also discuss and provide guidelines/call to action for future exposomics studies investigating the association of T2DM with exposomes in the context of both epidemiological and experimental approaches.
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2.
Multiple metal exposures and metabolic syndrome: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2011-2014.
Bulka, CM, Persky, VW, Daviglus, ML, Durazo-Arvizu, RA, Argos, M
Environmental research. 2019;:397-405
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Abstract
BACKGROUND Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. OBJECTIVES We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. METHODS Using data from the 2011-2014 National Health and Nutrition Examination Survey (n = 1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ≥ 3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. RESULTS After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. CONCLUSIONS These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.
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Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors.
Bortoluzzi, A, Furini, F, Scirè, CA
Autoimmunity reviews. 2018;(11):1097-1104
Abstract
Osteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide, with a strong impact on individual and population health. OA is a clinically heterogeneous disease presenting with different clinical phenotypes recognising systemic and local risk factors. The pathogenesis is multifactorial including constitutive features of the joint, non-modifiable and modifiable risk factors. Epidemiological studies highlight the link between metabolic syndrome and OA and the effect of interplay between immunological and metabolic processes is getting increasing emphasis because of to the discovery that metabolic syndrome is implicated in OA pathogenesis and progression. In addition, recent findings suggest a potential role of dietary factors in susceptibility and progression of OA. In this review, we summarise the most robust evidence on epidemiology and classical risk factors OA, also exploring the most recent evidence on metabolic changes and Mediterranean diet for OA as a possible target to impact on the natural history of the disease.
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The role of cadmium in obesity and diabetes.
Tinkov, AA, Filippini, T, Ajsuvakova, OP, Aaseth, J, Gluhcheva, YG, Ivanova, JM, Bjørklund, G, Skalnaya, MG, Gatiatulina, ER, Popova, EV, et al
The Science of the total environment. 2017;:741-755
Abstract
Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.
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[Potential sources of phthalates and bisphenol A and their significance in the development of metabolic diseases].
Mráz, M, Svačina, Š, Kotrlíková, E, Piecha, R, Vrbík, K, Pavloušková, J, Lacinová, Z, Vavrouš, A, Müllerová, D, Matějková, D, et al
Casopis lekaru ceskych. 2016;(3):11-5
Abstract
Nowadays, there is increasing evidence showing that the development of the metabolic syndrome combining obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia involves except of traditional risk factors (overnutrition, lack of physical activity, genetic predisposition) also the effect of environmental organic substances called organic pollutants or endocrine disruptors. These chemicals can be found in plastic covers, paints, flame retardants, exhaust gases, fertilizers as well as diverse daily utensils. Phthalates, used primarily as plasticizers, and bisphenol A, are among the most wide-spread members of this group.The aim of this article is to provide a basic overview of the relationship between phthalates and bisphenol A and the etiopathogenesis of the metabolic syndrome and to highlight their potential sources. According to the analysis of materials used for parenteral nutrition and urinary excretion of phthalate metabolites and bisphenol A in subjects on long-term parenteral nutrition we suppose that currently used medical materials are safe with respect to the exposure to both phthalates and bisphenol A and that home environment, especially cosmetic products, might constitute a more probable source of these substances.
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Endocrine disruptors: new players in the pathophysiology of type 2 diabetes?
Chevalier, N, Fénichel, P
Diabetes & metabolism. 2015;(2):107-15
Abstract
The prevalence of type 2 diabetes (T2D) has dramatically increased worldwide during the last few decades. While lifestyle factors, such as decreased physical activity and energy-dense diets, together with genetic predisposition, are well-known actors in the pathophysiology of T2D, there is accumulating evidence suggesting that the increased presence of endocrine-disrupting chemicals (EDCs) in the environment, such as bisphenol A, phthalates and persistent organic pollutants, may also explain an important part in the incidence of metabolic diseases (the metabolic syndrome, obesity and T2D). EDCs are found in everyday products (including plastic bottles, metal cans, toys, cosmetics and pesticides) and used in the manufacture of food. They interfere with the synthesis, secretion, transport, activity and elimination of natural hormones. Such interferences can block or mimic hormone actions and thus induce a wide range of adverse effects (developmental, reproductive, neurological, cardiovascular, metabolic and immune). In this review, both in vivo and in vitro experimental data and epidemiological evidence to support an association between EDC exposure and the induction of insulin resistance and/or disruption of pancreatic β-cell function are summarized, while the epidemiological links with disorders of glucose homoeostasis are also discussed.
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Breaking patterns of environmentally influenced disease for health risk reduction: immune perspectives.
Dietert, RR, DeWitt, JC, Germolec, DR, Zelikoff, JT
Environmental health perspectives. 2010;(8):1091-9
Abstract
BACKGROUND Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or "pattern" of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, and have been identified with the aid of large medical databases. OBJECTIVE We have described how an understanding of patterns of disease may be used to develop new strategies for reducing the prevalence and risk of major immune-based illnesses and diseases influenced by environmental stimuli. FINDINGS Examples of recently defined patterns of diseases that begin in childhood include not only metabolic syndrome, with its characteristics of inflammatory dysregulation, but also allergic, autoimmune, recurrent infection, and other inflammatory patterns of disease. The recent identification of major immune-based disease patterns beginning in childhood suggests that the immune system may play an even more important role in determining health status and health care needs across a lifetime than was previously understood. CONCLUSIONS Focusing on patterns of disease, as opposed to individual conditions, offers two important venues for environmental health risk reduction. First, prevention of developmental immunotoxicity and pediatric immune dysfunction can be used to act against multiple diseases. Second, pattern-based treatment of entryway diseases can be tailored with the aim of disrupting the entire disease pattern and reducing the risk of later-life illnesses connected to underlying immune dysfunction. Disease-pattern-based evaluation, prevention, and treatment will require a change from the current approach for both immune safety testing and pediatric disease management.
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Biomonitoring in Greenland: human biomarkers of exposure and effects - a short review.
Bonefeld-Jorgensen, EC
Rural and remote health. 2010;(2):1362
Abstract
CONTEXT Since 1997 the Arctic Monitoring and Assessment Programme (AMAP) has produced integrated assessment reports on the status of and trends in environmental persistent organic pollutants (POPs) in the Arctic ecosystem. Three reports on biomonitoring POPs and their health risks for Arctic populations were published in 1998, 2002, and 2009. ISSUE The present review summarizes data from Greenland on human monitoring of biomarkers of POP exposure and bioaccumulation and the determination of biomarkers for POP effects. The review focuses on hormone disruptive potentials and some genetic sensitivity biomarkers. The overview covers Greenlandic studies from 2000 to 2006. LESSONS LEARNED The Greenland biomonitoring studies showed general geographical and gender differences of bioaccumulated serum POP levels, which were primarily related to diet and lifestyle. A high intake of traditional Greenlandic diet (eg seal, whale, polar bear, and seabirds) together with smoking caused higher blood concentrations of POPs. The highest POP values were found on the east coast of Greenland. The receptor effect studies showed a general inverse relationship between high serum POP concentration and estrogen receptor (ER) and Ah-receptor (AhR) transactivity; in addition for men in the two West Greenlandic districts, Nuuk and Sisimiut, a trend towards increased induced AR activity was found. An observed trend to an opposite direction between the dioxin-like AhR and ER activity supports the perception of that dioxins exert an antiestrogen effect. In conclusion, the actual mixtures of serum POPs in Greenlandic Inuit have an endocrine disrupting potential. Comparisons between European and Greenlandic male serum POP levels showed significantly higher levels in Inuit; however, in the same study Inuit had significantly lower sperm DNA damage. Further studies are required to elucidate whether the serum POP related effects on hormone receptors and/or AhR are explanatory factors. 'The Arctic dilemma' is that along with the intake of the Greenlandic traditional diet that contains POPs, there are also a number of important nutrients, such as trace elements/antioxidants and marine unsaturated fatty acids which have favorable effects on health. However, a number of studies suggest that an increase in Western food items in the diet can lead to other health risks, such as the metabolic syndrome and its sequels increase in weight, hypertension, diabetes type 2, cardiovascular disease, and cancer, including breast cancer. To elucidate these aspects further studies are required, including those into biomarkers for exposure and effects, epigenetic contexts and the determination of relevant genetic polymorphisms, case-control as well as generation studies. Finally, there is a need for the development of new biomarkers to study the potential POP effects that inhibit the immune system and affect the development of the central nervous system.
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9.
[Mechanisms of extreme states in human].
Novikov, VS
Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine. 2000;(1):5-14
Abstract
Pathogenesis of extreme states during hypoxic hypoxia, exogenic and combined hyperthermia, aerial and immersion hypothermia is mainly associated with deterioration of reactivity and decline of functional reserves of the neuroendocrinal system, energetic dysbalance against more pronounced signs of anaerobic catabolism and recruitment of plastic resources of the body, activation of peroxide oxidation of lipids (POL), depletion of AOS potential with labilization of cellular membranes, and progressing changes in structural and functional relations within the antigenous/structural homeostasis. The determinacy of extreme state is influenced by initial status of the body functioning. The bodily extreme state has been found to depend on severity of asthenisation, peculiarities of the autonomous regulation, metabolic and immune status. Partial or full reversibility of decompensation disorders distinguishes extreme state from the critical (predeterminal) one. The relative adequacy of compensation and the principal possibility of a beneficial result are the necessary conditions for extreme state verification. Otherwise, in the lack of time for effective compensation typical syndromes of critical states may develop already during acute adaptation. There can develop partial insufficiency of a dominating functional system which will be compensated at the sacrifice of other organs and tissues. Sometimes extreme state may result in development of marginal or pathological states with human living activities preserved.