Triggle & Ding's group at Weill Cornell Medical College in Qatar
Cardiovascular disease (CVD) has long been a leading cause of death worldwide. Yet the relationship between CVD, diabetes and obesity — termed the metabolic syndrome — has become a critical consideration, more than studies of each condition individually. In Qatar, the rate of obesity and diabetes, among the native population, is among the highest, worldwide, so the need is great and the push is strong to make progress along these lines.
Investigators based in Doha, working with labs internationally and supported by QNRF’s National Priorities Research Program, are now positioned at the forefront of study into the metabolic syndrome. Their work is uncovering important clues that could help build awareness, refine treatment and improve quality of life among the millions worldwide affected by this complex tangle of conditions.
Dr. Christopher Triggle, Professor of Pharmacology, and Dr. Hong Ding, Assistant Research Professor of Pharmacology, at Weill Cornell Medical College in Qatar, working in conjunction with researchers at the University of Calgary, Canada, recently published a paper on relationship between fat, or adipose tissue, and the vascular system.
“Because there’s an association between obesity, cardiovascular disease and diabetes in particular, we wanted to know if the increase in perivascular fat [which lines the blood vessels] has an effect on blood vessel function, and the answer is that it does,” Dr. Triggle said.
According to the Dr. Triggle, there are many ways that fat tissue affects blood vessel function. In fact, fat also functions like an organ in the body, secreting hormones and other factors that scientists are just now starting to understand.
“Some of these factors have protective effects on the vasculature and some have negative effects,” Dr. Triggle said. “So the next question revolves around diabetes in the obese vs. diabetes scenarios in those who are not obese. We all have some level of fat tissue, and we do know that there is a relationship between obesity and not just CVD but also cancer.”
Beyond their study into body fat and circulation, Dr. Triggle and Dr. Ding have been working with NPRP funds to investigate the lining of blood vessels and how it is impacted by blood sugar levels, which are high in cases of diabetes.
“It’s interesting because we work particularly on the endothelium, which is that single layer of cells that lines all the blood vessels,” Dr. Triggle said, “and until 1980, nobody really thought that the endothelium was important. Now we know that the endothelium produces lots of factors that affect blood flow and cardiovascular function.”
Since joining WCMC-Q, Drs. Triggle and Ding have published fourteen articles and book chapters on the topic of endothelial dysfunction as related to diabetes. Their work focuses down to the molecular level, yet Dr. Triggle said environmental factors like diet and lack of regular exercise are suspects in the now-epidemic proportion of these diseases.
He explained the example of Nauru, a Pacific Island with a population that suffers from a high prevalence of diabetes. During the Japanese occupation, due to strict rationing of food that caused residents to live in a semi-starved state, the incidence of diabetes dropped. It was like “a non-approved study that shows you that fasting can be good for you. Although, of course, the severe level of food restriction placed on the inhabitants of Nauru had very negative effects on other aspects of health and is obviously NOT a regimen to copy.”
While the aforementioned lifestyle changes have played a strong role in the metabolic syndrome, evidence also suggests that it’s not so much about the amount of food one eats, as it is the frequency of eating and the nature of the food consumed, Dr. Triggle said.
“When I grew up in London, post-war, you really only had three meals a day, and you had built-in mini fasts between meals. That’s really not the case anymore for the majority of people today. So you can imagine what’s happening to your blood, with the continuous spiking of glucose levels—the body was not designed for that abuse.”
Having been awarded another NPRP grant in the fourth cycle, Dr. Triggle and Dr. Ding are embarking now on study into vascular motion, termed vasomotion, and are planning to collaborate with Oxford University, UK, to explore how blood flow may be reduced due to the combined effects of high glucose.
“The problem with diabetes is that the body doesn’t take up the glucose,” Dr. Triggle said. “In type one, this is due to a lack of insulin and in type two it’s due to insulin resistance. And if you have reduced blood flow, you’re also reducing the ability to dispose of the glucose—so we’re particularly interested in researching how glucose effects the microcirculation with these ideas in mind.”
In addition to these projects, Drs. Ding and Triggle are researching ways to improve the treatment of diabetes and are pursuing this goal by investigating how the most common drug used to treat type 2 diabetes, called metformin, works. Since metformin seems to protect the blood vessels from the effects of high blood sugar, their research into the endothelium could contribute greatly to the design of a better metformin-like drug.
“When I came here, I wasn’t expecting to conduct any significant research,” said Dr. Triggle. “I was hoping to continue with it through external collaborations, but when the opportunity and the support came in the second cycle of the NPRP, I was very excited. QNRF provides fantastic opportunities to get the research started. If you look at the research lab space at WCMC-Q, it’s more than doubled in size. Even with the new space, it’s becoming rapidly filled. It’s been a remarkable three years for us.”
Diabetic vascular disease: Relationship between hyperglycaemia and changes in growth factor receptor-mediated signaling.
LPI Name: Prof. Christopher Triggle, Weill Cornell Medical College - Qatar