Environmental Influences on Diabetes
Associated with the recent World Health Day of 8th April 2016 the first “Global Report on Diabetes” was published by the World Health Organization (WHO). The statistics on diabetes highlighted in this publication are alarming: diabetes has almost quadrupled since 1980 from 108 million to an estimated 422 million adults; diabetes is the number one cause of death, with 1.5 million people directly dying associated with diabetes in 2012. More than 43% of these deaths occurred in individuals under the age of 70 years old. The increase in type-2 diabetes (T2DM) has been observed to mirror the increasing prevalence in individuals who are overweight and obese. These numbers are also concerningly high, with 1 in 3 adults over the age of 18 being overweight and 1 in 10 being obese.
Excessive body fat is the strongest risk factor for the development of T2DM, while other risk factors include higher waist circumference, higher body mass index (BMI), and active smoking. Dietary patterns of high intake of saturated fat acids and total fat, low consumption of fibre, and high intake of sugar-sweetened beverages are also risk factors for T2DM and/or excess body weight. Early childhood nutrition also affects the risk of development of T2DM later in life with low birth weight, poor fetal growth, as well as high birth weight being associated with later development of diabetes.
The risk of additional health complications associated with diabetes are high. Ongoing management is necessary to manage blood sugars and monitor for microvasculature disease (retinopathy, nephropathy, and neuropathy) and microvasculature diseases of atherosclerosis and coronary artery disease. Lower limb amputation rates are 10 to 20 times higher among people with diabetes, and 7% of individuals with diabetes experience vision-threatening retinopathy. The estimate of end stage renal disease (ESRD) due to diabetes alone is 12 – 55%, about 10 times the risk of a population without diabetes. Finally, the rates of cardiovascular disease in individuals with diabetes is 2 to 3 times that of a population without diabetes.
With all this comes substantial financial cost. The direct annual cost of diabetes worldwide is estimated to be more than $827 billion (US dollars). And these costs are also on the rise with the increasing prevalence of diabetes. The relative economic burden associated with type-2 diabetes has been estimated to increase by 40 – 50% in the United Kingdom in the period from 2000 – 2060. The estimated costs associated with diabetes in the United States in 2012 was $245 billion, a 41% increase from the estimated of $174 billion in 2007. The average medical expenditure of an individual in the United States with diabetes is about $13,700 per year, of which about $7,900 is estimated to be due to diabetes.,
One of the things not considered or discussed in the WHO overview of diabetes is the potential impact of environmental risk factors on the development of diabetes. Exposure to environmental risk factors has been documented to have an inverse relationship with socioeconomic status, and a lower socioeconomic status has a known impact on health outcomes. As the prevalence of diabetes is highest across all age groups in men in individuals of a lower middle-income status, and is growing the fastest in low- and middle-income countries, the potential contribution of this as a factor should not be neglected.
Environmental toxins have the ability to affect genetic transcription, disrupting DNA methylation as well as altering the organisation of chromatin which serves to prevent DNA damage and to control gene expression and DNA replication. Additionally, epigenetic changes such these have the potential to have transgenerational effects.,
Exposure to a variety of environmental toxins has been associated with or are being studied to investigate their relationship with the development of many types of cancer, respiratory disease, cardiovascular disease, infertility, allergies, autoimmune disease, and many other conditions. Exposure to environmental toxins can occur through the air, contaminated drinking water, and food that is being eaten. Many of these environmental pollutants are persistent (thus known as persistent organic pollutants [POPs]), that is they have very little or no degradation with time and thus will continue to accumulate in the environment.,,,,
Environmental pollutants also have been shown to have associations with obesity and diabetes. Endocrine disrupting chemicals (EDCs) can have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. EDCs have the potential to affect hormone biosynthesis, metabolism, or action resulting from the acts of hormones in the body. EDCs broadly include environmental pollutants including organochlorinated pesticides and industrial chemicals, plastics and plasticisers, fuels, and many other chemicals that are present in the environment or are in widespread use.,
Bisphenol A is a known endocrine disruptor. High levels of BPA have been correlated with obesity, diabetes, cardiovascular diseases, polycystic ovarian disease or low sperm count. Urinary BPA excretion and HbA1c levels were observed to be significantly associated in 4389 adults with diabetes. In another recent study, BPA levels were found to be associated with insulin resistance in overweight or obese children between 3 – 8 years of age. In analysis of data from the Nurses’ Health Study, BPA and phthalate exposures was found to possibly be associated with the risk of T2DM among premenopausal women but not post-menopausal older women. This was hypothesised to be due to the enhanced endocrine interference of oestrogen receptors of pancreatic β cells in premenopausal women who would have higher levels of oestrogen.,,,
At environmentally relevant doses, BPA has been observed to inhibit the release of adiponectin which helps to protect humans from metabolic syndrome. BPA has also been observed in animal models at low doses to induce an increase in pancreatic beta-cell insulin content, and after exposure of only 4 days led to the development of chronic hyperinsulinemia and altered glucose and insulin tolerance tests. Mice exposed to BPA in utero and the neonatal period also developed glucose intolerance.,
Dioxins also are persistent organic pollutants classified as EDCs that have been suggested in several epidemiological studies to be associated with the development of diabetes. A high serum dioxin level has been shown to be an independent risk factor in a recent study for the development of diabetes, independent of age and BMI in both men and women.,,
In a survey of 2,016 adult participants performed by the National Health and Nutrition Examination Survey (NHANES), diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of 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) after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference.
One observation from these studies was that obese persons who did not have elevated POPs were not at elevated risk of diabetes. This suggests that the POPs rather than the obesity was responsible for the association.
Core interventions for the management of diabetes and the related complications include lifestyle changes (healthy diet, exercise, smoking cessation), blood sugar management, regular exams for early detection of complications, and medications to control cardiovascular risk if necessary. However, as these other factors may also play a role they should not be neglected with a holistic approach to diabetes treatment. Some of these may be addressed by more diligence in avoidance of products which lead to exposures to these things.
Bisphenol A (BPA) is found in polycarbonate plastics. Polycarbonate as a material is used for many types of food and drink packaging. The primary source of exposure to BPA for most people is through the diet as it leaches into food from items such as polycarbonate tableware, food storage containers, water bottles, the internal protective coating of canned foods, and baby bottles. The degree to which BPA leaches from these materials into food depends most on the temperature of the liquid or bottle, with hotter food leading to higher amounts. BPA can also be found in breast milk with maternal exposure.
People are exposed to dioxins primarily by eating food, in particular animal products, contaminated by these chemicals. Dioxins are absorbed and stored in fat tissue and, therefore, accumulate in the food chain – including the end user (humans) who are consumers. More than 90 percent of human exposure is through food. Environmental controls have significantly reduced the introduction of new industrial sources of dioxin. However, as this chemical also is a POP, ongoing exposure will continue to occur.
Although avoidance would be a highest priority, other things to reduce the impact of exposure to environmental pollutants may be necessary. BPA exposure is associated with oxidative stress and inflammation. Other environmental chemicals such as polycyclic aromatic hydrocarbons and volatile organic compounds also have been shown to oxidative stress in a dose-response fashion. Significantly, oxidative stress markers were observed to affect the measurements of insulin resistance.,,
N-acetylcysteine has been found to attenuate oxidative damage associated with BPA exposure and related cognitive dysfunction. Quercetin also has been shown to mitigate oxidative damage to the liver and kidneys associated with BPA. Silybum marianum, or milk thistle, has been studied in other settings of environmental related oxidative damage, and has been observed to have a substantial protective effect and free radical scavenging mechanism. Many other plant species although they have not been studied specifically in the setting of BPA also may have a beneficial effect.,,,
Berberine is a compound sourced from botanical species such as Oregon grape, goldenseal, and barberry. Berberine has a multitude of actions which may benefit an individual with diabetes. It serves as an antioxidant and anti-inflammatory, but also plays significant roles which are necessary for individuals with diabetes. Berberine has been shown to improve insulin resistance, promote insulin secretion, inhibit gluconeogenesis in liver, and stimulate glycolysis in peripheral tissue cells. Berberine also modulates the gut microbiota and regulates lipid metabolism.,,,
Lipoic acid is another antioxidant which has many roles in the treatment of diabetes and has some evidence for mitigating BPA toxicity. Lipoic acid also has evidence for reducing the peripheral neuropathy complications of diabetes and improving the use of glucose. Lipoic acid has been found to support the reduction of HbA1c levels as well as improve endothelial function.,,,
A combination of chromium picolinate and biotin has been shown to improve glucose management and several lipid measurements in patients with poorly controlled diabetes.
With a more holistic approach to the treatment of diabetes, many of these agents can be included as supplements in addition to dietary and lifestyle changes which focus on minimising environmental toxin exposures.
 Sun Q, et al. Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses’ Health Study (NHS) and NHSII cohorts. View Abstract
 Hugo ER, et al. Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect. 2008 Dec;116(12):1642-7. View Abstract
 Alonso-Magdalena P, et al. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006 Jan;114(1):106-12. View Abstract
 Calvert GM, et al. Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med. 1999 Apr;56(4):270-6. View Abstract
 Lee DH, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. 2006 Jul;29(7):1638-44. View Abstract
 Kabuto H, et al. Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci. 2004 Apr 30;74(24):2931-40. View Abstract
 Jain S, et al. Protective effect of N-acetylcysteine on bisphenol A-induced cognitive dysfunction and oxidative stress in rats. Food Chem Toxicol. 2011 Jun;49(6):1404-9.
 Kiruthiga PV, et al. Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes. Basic Clin Pharmacol Toxicol. 2007 Jun;100(6):414-9. View Abstract
 Poh ZX, Goh KP. A current update on the use of alpha lipoic acid in the management of type 2 diabetes mellitus. Endocr Metab Immune Disord Drug Targets. 2009 Dec;9(4):392-8.
 Sola S, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation. 2005 Jan 25;111(3):343-8. View Abstract
 Singer GM, et al. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006 Dec;8(6):636-43. View Abstract
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