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So, I have published a number of papers in my postdoc, but here we have the first one from Donna Arnett’s GOLDN study; which is funded with the R01, which funds me (hence, it is important to start producing papers on this dataset).

This paper is the genetic follow-up to a previous paper, which is still under review. I am looking at lipoprotein diameters as a marker of disease, and hopefully, as a risk predictor of disease. I found that one way to use this unusual phenotype was to look at the relations between the three types of lipoprotein diameter: very-low density (VLDL), low-density (LDL) and high-density (HDL). Interest in lipoprotein diameter was first aroused when it was found the people with atherosclerosis and cardiovascular disease has smaller LDL particles. It was then found that insulin resistance (the metabolic abnormality that underlies Type 2 Diabetes and some other conditions) also segregated with smaller LDL. Many lipidologists and physiologists assume that VLDL, LDL and HDL diameters vary linearly – that is, as your LDL diameter decreases, so does your HDL diameter. But your VLDL diameter increases. Therefore, insulin resistance, and cardiovascular problems might be identified by looking for people with small LDL and HDL, but large VLDL diameters. I found that this was only partially the case. Insulin resistance is indeed marked by smaller LDL and HDL particles. However, VLDL varies independently of these. Large VLDL in itself does not seem to be a marker of insulin resistance. However, if it occurs WITH small LDL and HDL particles, it separates out those with really severe metabolic disturbances (very high triglycerides, waist circumferences and blood pressure) from all those with insulin resistant features.

I am STILL trying to get this work published (despite winning numerous awards for it). However, the paper I am sharing today looks at trying to identify this ‘high risk’ category from all those with insulin resistance. That is, it looks at marking out the most severe metabolic disturbances and hopefully with thus help me identify the underlying biology of the worst insulin resistance. I took all those with the metabolic syndrome, and found a difference in the stop codon of the lipoprotein lipase gene between those with very large VLDL and those without.

If you are still awake, here is a preliminary PDF of my paper:

Wood et al, 2011, LHD and a weblink to the journal.

So where do I go for here? Well, I would like to find out:

-Does this predict, or just occur alongside disease?

-Can we use this genetic information (with other information) to predict who is at risk of developing type 2 diabetes and prevent its occurence?

-Can we use this genetic information to understand the underlying biology of severe insulin resistance? In particular: what lifestyle factors ’cause’ it? And ym main fascination: if genes affect insulin resistance severity, and genes can be turned ‘on and off’ by the environment: how can we use the environment (what we eat, exercise, ??sleep patterns??) to turn off genes that lead to type 2 diabetes and / or cardiovascular disease? Can we prevent these metabolic disturbances? Can we stop them in their tracks?

I have a great job :)))

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