Active Low-Carber Forums - View Single Post - Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity

Ludwig is correct in pointing out that the truth is far more complicated. Over the past few years when asked why I was eating the way I do, my response was that I was trying to better manage my insulin, and to improve my health.

Interesting how smart people who did not garner a lot of recognition when they were publishing findings in the past have contributed information that supports the findings in this Mendelian Randomization study: Dr. Joseph Kraft who correctly analyzed the OGTT and found flaws in how the tests were traditionally interpreted, and those who did early research in the 60s and 70s (Dr. Bruce Lipton and other pioneers) which led to the field of Epigenetics. Epigenetics correctly viewed how genes can be expressed (turned on) or not (turned off) by environmental influences which includes diet. The human genome does not mutate that rapidly, but gene tendencies and how they are expressed are largely influenced by environment at the cellular level.

Quote:

From CONCLUSIONS:
A recent Mendelian randomization analysis (26) cast doubt on the carbohydrate–insulin model, finding no evidence for a causal relationship between fasting insulin and body mass index (BMI)7. However, in the carbohydrate–insulin model, it is insulin secretion in response to carbohydrate, not fasting insulin, that influences weight gain, in part because the latter is strongly confounded by insulin resistance (5). Indeed, insulin resistance in adipose tissue protects against weight gain, as demonstrated by the fat-specific insulin receptor knockout mouse model (27). Therefore, we selected genetic variants identified by large genome-wide association studies associated with glucose-stimulated insulin secretion, not fasting insulin, to more appropriately test the carbohydrate–insulin model.

GENETICALLY DETERMINED BMI NOT ASSOCIATED WITH HIGHER INSULIN-30

Finally, we used bidirectional Mendelian randomization to further examine the directionality of the relationship between insulin-30 and BMI (Fig. 1B). Instead of using the combined insulin-30 associated variants as an instrument, we performed Mendelian randomization in the reverse direction, using 97 loci known to be associated with BMI in GIANT (33) as an instrument set (Fig. 2B). We tested this set for association with early insulin secretion in the MAGIC data. We found no evidence of a reverse causal effect for BMI on insulin-30 (β = 0.115, P = 0.43, heterogeneity P = 0.13).

While further studies are required, this information confirms a few thoughts about obesity and health related to diet:
1) The contention that there is no one diet that is healthy for all is true when accounting for one's genetic predisposition and many other factors that must be considered,
2) For people like me who likely have a higher insulin release in response to certain foods (carbohydrates), this enables us to continue to effectively manage our health by following a low carb approach. I know I'm a hyperinsulin responder to processed and unprocessed carbohydrates,
3) Until further studies are done to explore implications of diet in the context of genetics and MR, following an N=1 approach to better learn what works is the best approach to optimize one's WOE for health and longevity.

I'm comfortable with this and am eager to learn from further studies.