Diabetes type II is an increasing problem in the Western world. But while some people develop this disease quickly along with a bit of weight gain, others can stay disease free at a much higher BMI. The severity of complications due to diabetes is very unpredictable as well and can vary greatly between individuals. While there is a lot that we don´t understand about diabetes, we do know that the causes are both environmental and genetic. To find out more we need to use both aspects in a scientific discipline: metabolomics.Subtypes of pre-diabetics
“When you do metabolomics, you measure small molecules present in the system, at a certain time,” explains Koko Wei, recently defended PhD student at the Sino- Dutch Centre for Preventive and Personalized Medicine. “These small molecules are the sum of your genetic make-up and your environmental behavior, thus the perfect way to study diabetes type II.” During her PhD, she used metabolomics to identify subtypes of pre-diabetics, ultimately to predict whether they will develop diabetes and how severe they would be affected by it. Her unique background in the integration of western and traditional Chinese medicine served as a starting point for her research.Early diagnosis of individuals
In traditional Chinese medicine, early diagnosis of individuals with a cluster of symptoms is common practice. The Chinese doctor will ask questions, feel your pulse, look at your tongue, and prescribe a remedy in earlier stages than their Western counterparts. Part of this diagnosis is that the Chinese doctor will determine your subtype which may carry a poetic name like ‘Qi-yin deficiency’ and is based on symptoms. Koko Wei’s main research question was whether these subtypes can be diagnosed reproducibly, and confirmed with solid metabolomics measurements. Perhaps these early subtypes can be of use in diabetes research.
“We collected fifty male subjects here in Holland, who weren’t diabetics yet, but may be at risk of becoming one,” Wei explains. “That means that they had a blood-glucose level of 6.1-6.9 millimole per liter, and a BMI of 25 or more. According to WHO guidelines, you only are a diabetic with a blood glucose level , regardless of your BMI.” To validate the diagnosis process, three different Chinese doctors diagnosed these men in one of three Chinese medicine subtypes. When those turned out to be consistent, the blood and urine of all participants were collected and analyzed.128 unique metabolites
At TNO, Wei performed the GC-MS measurements and only selected those metabolite peaks which were detectable in 80% of samples. 128 unique metabolites where measured and partly identified. “The exciting moment was when we performed a Principal Component Analysis on our data,” Wei continues. “This is a non-biased technique, which means that we didn’t use the diagnoses of the Chinese doctors in grouping these data points, just the metabolomics results. We discovered two distinct groups, one corresponding very much with a Traditional Chinese subtype. The latter showed more disturbances of carbohydrate metabolism and renal function. This means that – although we don’t know how many these people will become diabetics patients or how much complications they will suffer- that it is possible to identify subtypes at a very early stage by combining Chinese medicine diagnosis and metabolomics. And that these subtypes can be properly measured.”
The next step will be to follow these kinds of pre-diabetics for a longer period with intervention or challenge tests, to see the effect of the subtypes on medication and complication development. Koko has recently finished her PhD, and will continue working in the field of nutritional research and preventive health care.