Tuesday, April 3, 2012

What's Your Metabotype? Researchers Identify Distinct Metabolic Responses to High & Low GI Carbohydrate Meals in Healthy, Non-Obese Individuals

Image 1: Firstly, obesity is not the only determinant of metabolic derangement. And secondly, if your diet does not match your Metabotype, it's unlikely you'll ever make it from the left to the right (img. DrPinna.com)
A common motif that arises time and again, when people are discussing the "correct" amount of carbohydrates in the "optimal" diet is that of individuality, respectively the individual susceptibility to the detrimental and beneficial effects of carbohydrate consumption. Interestingly enough, practical (not genetic) scientific evidence for the existence of this inter-individual differences is scarce. And while the general consensus is that obesity or "body fatness" is the central determinant of insulin resistance and subsequently "carbohydrate intolerance" the increasing amount of non-obese "skinny-fat" type II diabetics does tell another story. Against that background the recently published data from an experiment that has been conducted by a group of Californian researchers are of particular importance, especially as they do not confirm the usual cliché that you can predict the individual response to an high and low glycemic index meals based on body fat levels, alone.

You know your phenotype, but what's your metabotype?

The main intention of the study, which involved 24 healthy, non-obese pre-menopausal women (20-50y), was to identify distinct metabotypes within the healthy population, in order to develop a better understanding of the (in some cases) fundamental inter-individual differences to identical carbohydrate challenges. To this ends the study participants had to consume a standardized 3-day run-in diet (56% carbs, 14% protein, 30% fat; same as test meal) before consuming a standardized high (GI 76.7; GL: 86.3; 833kcal) or low GI (GI: 36.5; GL: 42.1; 835kcal) breakfast after an overnight fast.
Figure 1: Body composition and non-esterified fatty acid levels of the women in the different response groups (RG1-3) the scientists identified in statistical ex-post analyses (data adapted from Krishnan. 2012)
And while the majority of subjects (n = 18) showed the expectedly high / low glucose and insulin response in response to the high and low GI test meals, there were 6 outliers whose insulin and leptin responses clearly show that not all carb-consumers are created equal.

Insulin or leptin resistance? Devil or deep blue sea?

The principal component analysis (PCA) the scientists conducted revealed that, when compared to the normal-responders in RG1,  ...
  • the women in group RG2 had lower postprandial leptin, higher insulin and higher glucose relative
    responses to the two meal challenges (cf. figure 2),
  • the women in group RG3, on the other hand, had a higher leptin and glucose, yet similar insulin responses.
Further analysis revealed that these responses exhibited a distinct temporal patter, with higher postprandial glucose, higher early and mid-postprandial leptin combined with similar postprandial insulin response in the RG3 group and lower glucose responses than RG3 and similar glucose and leptin responses to RG1, but the highest insulin response in the women with an RG metabotype.
Figure 2: Glucose, insulin and leptin (AUC, range scaled for high & low GI meals) in the of the women in the different response groups (RG1-3) the scientists identified in statistical ex-post analyses (data adapted from Krishnan. 2012)
These patterns (cf. figure 2), which are suggestive of baseline insulin and leptin resistance in the abnormal responders in RG2 and RG3, respectively, do by no means correspond to conventional nutritional standards, by which the leanest women, i.e. the women in RG2, should exhibit the greatest insulin sensitivity and the the women in RG3, who had the lowest NEFA levels the greatest leptin sensitivity.

6 outliers in 24 sounds less than 25% of the population, right?

Image 2: If you invite 5 friends for lunch, one person at the table will handle the carbohydrate content of the meal differently
Despite the small number of abnormal responses, the real-world experience of thousands of dieters should be evidence enough for the existence and significance of this "errant metabolic fine-tuning", as the researchers aptly label the observed deviations from the "norm". The limitations of the current study
  1. the subjects were exclusively premenopausal women
  2. only three subjects in the "non fine-tuned" groups, 
  3. no mechanistic explanation for the observations, 
  4. possible influence of the run-in diet, 
  5. only a single challenge with each of the test meals
should thusly not be the only reasons for further studies into a) the existence and underlying physiological and genetic mechanisms of different metabotypes, and b) the validity of this simple approach to metabo-typing. If the latter "worked", or I should say if a simple meal challenge would suffice to reliably classify your metabotype, this would after all offer a very valuable tool to optimize dietary interventions..

And what's more, if it was recognized as such by the medical establishment (in this context it should be mentioned that co-author John W. Newman works at the Western Human Nutrition Research Center, Obesity and Metabolism Research Unit of the USDA) study was conducted by scientists from the USDA) it would open a door to a differential and thusly way more effective treatment diet-related disease. And, at least according to the data from the study at hand, for 25% of the normal-weight, ostensibly healthy part of the (female) population, this would not be the currently advocated high-carb, low-fat diet