EASO New Investigators United Spotlight: Eveline Dirinck

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Hello Eveline. It’s great to have the opportunity to meet with you. For those of you who don’t know Eveline, here is a brief biography.

Eveline Dirinck was born on February 22, 1982. After finishing High School, where she studied science and mathematics, she started Medical School at Antwerp University. Her research during Medical School focused on the value of insulin sensitivity tests in a population with obesity. She graduated cum lauda in 2007 after which she began to train as an internist. In August 2009, she started work on her PhD thesis at the department of Endocrinology, Diabetology and Metabolism at Antwerp University Hospital. In 2014 she graduated as an internist and in July 2015 she graduated as an endocrinologist. In April 2016, she successfully defended her PhD thesis entitled “Endocrine disrupting chemicals: from accumulation to their role in the global “neuro-endocrine” epidemic of obesity and its metabolic consequences.” Since September 2015, she has worked as a member of staff at the department of Endocrinology, Diabetology and Metabolism of Antwerp University Hospital.

Eveline, we would love to learn more about your country and the area you live in; what is it like?

I live and work close to Antwerp, Europe’s second biggest port and a very international city. Antwerp is a trending, lively city that offers many cultural and leisure activities to take my mind off science. Antwerp is one of the main cities of Belgium, a little country located at the very heart of Europe with beautiful ancient cities with great museums, theatres and a vibrant music scene, lovely countryside, and true appreciation of good food and drink (it’s extremely hard to find a really bad restaurant in Belgium).

How did you come to enter this field?

There are several reasons I became interested in obesity. As a student, I was intrigued by the fact that so many questions still needed to be answered in the field of obesity. Our weight is a key determinant of our general health, and the mechanisms controlling it are fascinating in their complexity. During Medical School, I already initiated my research efforts in the department with Professor Van Gaal. I still feel privileged to work with him. After an international career of 30 years in the field of obesity, he remains inquisitive and enthusiastic about new theories and  developments.

Congratulations on winning the highly competitive 2016 EASO New Investigators Best Thesis prize. Please help us learn more about your thesis and present research interests:

Below is a synopsis of my thesis:

Summary

Obesity is quickly becoming one of the most significant human health threats worldwide. Traditionally, the increase in obesity is attributed to an increased caloric intake and a concomitant significant reduction in physical activity and energy expenditure  However, this does not fully explain the extent of the current epidemic. Concurrent with the obesity epidemic, is the exponential increase of human exposure to synthetic chemicals worldwide. Several chemicals are known to mimic, enhance or inhibit the action of hormones and are therefore called endocrine disrupting chemical(s) (EDC(s)). Today, we are dealing with thousands of these chemicals, either as individual compounds or as part of a potentially dangerous cocktail.  It has been postulated that certain chemicals potentially play a causative role in the development of obesity, by affecting or causing changes in fat mass.

In this PhD, attention is focused on polychlorinated biphenyls (PCBs), the organochlorine pesticide DDT and its metabolite p,p’-DDE, and phthalates. PCBs are odorless, tasteless, viscous liquids whose chemical properties make them excellent dielectric and coolant fluids. Therefore, they were used worldwide for various industrial purposes. There are 250 different PCB congeners and commercially available products always contained a mixture of several congeners. The production of PCBs was banned in the 1970s. Unfortunately, since PCBs are extremely resistant to biological degradation, significant bioaccumulation leads to an ongoing human exposure. The most notorious organochlorine pesticide is dichlorodiphenyltrichloroethane, or DDT. DDT is metabolized by the human body into dichlorodiphenyldichloroethylene (p,p’-DDE). DDT was used in abundance in the western world until its ban in the 1960s. Unfortunately, DDT remains a popular pesticide in the developing world to increase agricultural production and to control various vectors spreading diseases like malaria. Similar to PCBs, OCPs are very resistant to biological degradation and are labeled persistent organic pollutants (POPs). Today, both PCBs and p,p’-DDE are found in humans around the globe. Phthalates are an essential compound of plastics, lending it flexibility, transparency and durability. Phthalates are easily released from the plastic  into the environment, a process that is accelerates as the plastic ages and breaks down.

Numerous studies have investigated the link between exposure to EDC and obesity and obesity related disorders such as diabetes and the metabolic syndrome. However, the description of the obese or diabetic state, often relied on crude measures such as body mass index, or selfreporting of disease states. Therefore, this study aimed to provide a very detailed description of lean, overweight an obese subjects in terms of body composition, metabolic health, other related factors such as physical activity and toxicological analyses. The overweight and obese group were treated with dietary measures or bariatric surgery and analyses were repeated after 3, 6 and 12 months.

Firstly, serum levels of POPs are lower in obese individuals compared to lean individuals. A potential explanation may be found in the dilution capabilities of these substances. As these lipophilic chemicals are preferably stored in adipose tissue, a higher percentage of body fat will lead to fast and efficient storage, with lower serum levels as a consequence. In adipose tissue, the concentrations of PCBs and p,p’-DDE were identical in both subcutaneous and visceral fat. This implies that, although the serum levels were lower, the total amount of chemicals in an obese individual are higher given the higher amount of fat mass. Despite the identical absolute concentrations in both fat compartments in weight stable conditions, only the subcutaneous fat was significantly negatively associated with PCB serum levels. During weight loss, POP serum levels increased substantially, but the rise was more pronounced in those patients that relatively lost more visceral fat. These data suggest that the obesogenic effect and dynamics of POPs might be more pronounced in the visceral fat compartment.

The second part of this thesis focused on the link between endocrine disrupting chemicals and disturbances of glucose metabolism. Our analyses indicate a positive link between disturbed glucose tolerance, and the total amount of POPs in the human body. We could not identify a compensatory rise in insulin secretion. This finding seems to support the hypothesis of direct POP toxicity to the beta-cell as a potential causative factor in the development of type 2 diabetes mellitus. Even after correction for known risk factors such as visceral adiposity and a positive familial history,  a statistically significant role for POPs on the risk of abnormal glucose tolerance was identified. These data further strengthen the hypothesis of the diabetogenic capacities of POPs in vivo.  Apart from POPs, focus was also put on phthalates and their link with glucose metabolism. In our overweight and obese population, exposure to phthalates was associated with markers of increased insulin resistance, decreased insulin sensitivity and possibly impaired beta cell function.

A third part focused on the link between POPs and metabolic health, using both the standard definition of the metabolic syndrome, as a more elaborate definition of metabolically healthy versus unhealthy obese (MHO versus MUO) that took into account additional information on insulin resistance and inflammation. Our analyses indicate that PCB serum levels were higher in MUO vs MHO, but not in individuals with the metabolic syndrome versus individuals without the metabolic syndrome. The increment in PCB serum levels during weight loss was significant, but did not differ between groups. After weight loss, the resolution of a metabolically unfavorable state was not influenced by the PCB serum levels at baseline. From a clinical point of view, these finding are reassuring as they seem to suggest that current PCB levels in a Belgian population are not capable to impair the metabolically favorable changes related to weight loss.

Finally, since thyroid hormones are key players in the control system of our metabolism, with, amongst others, a pivotal role in energy metabolism, the relation between thyroid function and PCBs and their hydroxylated metabolites was investigated. We could link circulating free T4 levels to serum levels of several PCBs and hydroxylated PCB metabolites, but we didn’t identify a link with thyroid stimulating hormone (TSH).

The results of this study contribute to the increasing amount of data regarding the obesogenic and diabetogenic  capacities of a number of chemicals. At present, the data regarding this hypothesis are very suggestive but not yet categorically conclusive. Obesity and its related conditions are difficult to treat, and health care related costs of these disease states are towering. The obesogen hypothesis should remain an important research area as reduction of exposure offers a unique preventive possibility at population level.

Fascinating and important work on the role of chemical endocrine system disrupters. What are your future career plans, Eveline?

I wish to continue my efforts in unraveling the link between endocrine disrupters, obesity and metabolic diseases. In addition to obesity and type 2 diabetes, I have a special interest in management of diabetic foot ulcers and in the pre- and postoperative management of bariatric patients.

Aside from your professional interests, what are your hobbies and interests?

I am married to the most wonderful man in the western hemisphere, and together we have 2 adorable twin boys, aged 5. Although my husband is not a physician, he understands the responsibilities that come with my clinical and research work and is extremely supportive. Coming home to my 3 men every evening is the main reason I am a very happy woman.

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