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      Persistent organic pollutants as risk factors for type 2 diabetes

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          Abstract

          Type 2 diabetes mellitus (T2DM) is a major and fast growing public health problem. Although obesity is considered to be the main driver of the pandemic of T2DM, a possible contribution of some environmental contaminants, of which persistent organic pollutants (POPs) form a particular class, has been suggested. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes which enable them to persist in the environment, to be capable of long-range transport, bio accumulate in human and animal tissue, bio accumulate in food chains, and to have potential significant impacts on human health and the environment. Several epidemiological studies have reported an association between persistent organic pollutants and diabetes risk. These findings have been replicated in experimental studies both in human (in-vitro) and animals (in-vivo and in-vitro), and patho-physiological derangements through which these pollutants exercise their harmful effect on diabetes risk postulated. This review summarizes available studies, emphasises on limitations so as to enable subsequent studies to be centralized on possible pathways and bring out clearly the role of POPs on diabetes risk.

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          Glucose clamp technique: a method for quantifying insulin secretion and resistance.

          Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
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            A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002.

            Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.
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              Low Dose Organochlorine Pesticides and Polychlorinated Biphenyls Predict Obesity, Dyslipidemia, and Insulin Resistance among People Free of Diabetes

              Background There is emerging evidence that background exposure to persistent organic pollutants (POPs) are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study. Methodology/Principal Findings The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA–IR) were study outcomes at 2005-06 (year 20). The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves. Conclusions/Significance Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism.
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                Author and article information

                Contributors
                ngwaelvis73@yahoo.fr
                apkengne@yahoo.com
                mma_tiedeu@yahoo.com
                edithmofo8818@yahoo.fr
                sobngwieugene@yahoo.fr
                Journal
                Diabetol Metab Syndr
                Diabetol Metab Syndr
                Diabetology & Metabolic Syndrome
                BioMed Central (London )
                1758-5996
                30 April 2015
                30 April 2015
                2015
                : 7
                : 41
                Affiliations
                [ ]Laboratory of Molecular Medicine and Metabolism, Biotechnology Centre Nkolbisson, Biotechnology Centre Nkolbisson, Yaounde, Cameroon
                [ ]Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
                [ ]Department of Medicine, University of Cape Town, Cape Town, South Africa
                [ ]Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon
                [ ]National Obesity Center, Yaoundé Central Hospital and Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, P.O. Box 7535, Yaoundé, Cameroon
                Article
                31
                10.1186/s13098-015-0031-6
                4435855
                25987904
                dfe812c6-699d-4752-b0e0-ce49ed935e6f
                © Ngwa et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 September 2014
                : 2 April 2015
                Categories
                Review
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                © The Author(s) 2015

                Nutrition & Dietetics
                type 2 diabetes,persistent organic pollutants,in utero exposure,insulin secretion,insulin resistance

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