Anyone interested in explaining a scientific study for me?

The objective was to determine whether the risk of T2D associated with TCF7L2 is modified by the glycemic load (GL), glycemic index (GI), cereal fiber content, and total carbohydrate content of the diet.
T2D cases (n = 1140) and controls (n = 1915) from the Nurses’ Health Study were genotyped for TCF7L2 (rs12255372). Dietary intake was assessed with a semiquantitative food-frequency questionnaire.
Significant differences in odds ratios (ORs) of T2D associated with the TCF7L2 genotype between high and low strata of GL (P = 0.03) and GI (P = 0.05) were suggested. Compared with the GG genotype, multivariate-adjusted ORs (95% CI) of T2D associated with the TT genotype were 2.71 (1.64, 4.46) and 2.69 (1.64, 4.43) among individuals in the highest tertile of GL and GI, respectively. Corresponding ORs (95% CIs) among individuals in the lowest tertiles of GL and GI were 1.66 (0.95, 2.88) and 1.82 (1.11, 3.01). The risk of T2D associated with the TCF7L2 single nucleotide polymorphism did not significantly differ by cereal fiber or carbohydrate intake.
Carbohydrate quality and quantity modified risk of T2D associated with TCF7L2, which suggests that changes in risk attributable to the TCF7L2 variant are magnified under conditions of increased insulin demand.

*my specific question is that the bolded statements above the conclusion and within the conclusion seem to be contradictory. what am i not getting? if there is anyone out there who loves to teach, could you also explain the concept of ‘odds ratio’ and the numbers that follow? i know CI is ‘confidence interval’, but i don’t know how that concept applies to OR (odds ratio). i already understand the basics of the genotype/snp/risk allele terms. thanks.

This study entitled “TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women” looked at women who had the genotype TCFL2 and whether their carb dietary intake was “associated” with T2 rates. Note my use of the term associated. The article doesn’t use that term, they say “modified” suggesting that people who changed their diet altered the course of their diabetes development. Harvard has a legacy of wildly exaggerated and misinterpreted observational studies (thank you Walter Willett) and I claim this is just another one in a long line of studies that should be taken with a 1lb grain of salt.

So in summary, this is an observational study, not an intervention study. Women with TCFL2 who developed T2 were found to have had a higher Glycemic Load (GL), Glycemic Index (GI) but no differences were found in fiber or total carb intake. This was an association suggesting either that GL/GI “caused” T2, that T2 caused a higher GL/GI or that “something else” (like insulin resistance) caused both T2 and higher GL/GI.

It is “wrong” and inappropriate to interpret this study as suggesting that eating a low GI/GL diet will reduce T2 risk.

ps. Confidence interval tells you in what range 95% of the results fell into. Odds Ratio (OR) is the relative risk, so an OR of 2 means that something occurs twice as often. So when they quote “ORs (95 %CI)” of “2.71 (1.64, 4.46)” that means that the resulting risk in patients in the highest tertiary (third) of GL/GI was 2.72 times higher than those in the lowest tertiary. And further the 95% of the patients had ORs between 1.64 and 4.46.

what does it mean that the women who developed T2 had a higher Glycemic Load and Glycemic Index? That means that they ate foods that were high on the glycemic index? or that they just had higher blood sugars? very confusing. could you try one more time to explain it to me?

The Nurses Health Study asked nurses to fill out questionnaires about their diet. What they found was that nurses that reported eating higher glycemic foods also had higher rates of T2. The study didn’t look at causes, only that eating higher glycemic foods was associated with higher rates of diabetes. It wasn’t really about blood sugars, it was about being diagnosed with T2. Does that help?

when you explain it that way, one possible conclusion is that if you have the risk allele for the TCF7L2 gene and you eat lower carb, you will not develop diabetes. that is how i interpreted it originally.
so i don’t understand why you wrote
"It is “wrong” and inappropriate to interpret this study as suggesting that eating a low GI/GL diet will reduce T2 risk."

i have one risk allele for the TCF7L2 gene, and it i eat lower carb, i can stay in a normal bg range. if i eat something like a slice of pumpkin pie, i will hit 200 at the one hour mark.

i will have to read your explanation a couple of times, because i still see a contradiction in the study between the conclusion and the statement above the conclusion.

I think it would be just as appropriate to say that women with the TCF7L2 gene who develop diabetes will tend to be driven by carb hunger and additiction and will eat higher GL/GI diets. The study provides no evidence that the high GL/GI diet “causes” the emergence of diabetes. And by correlation the study provides no evidence that eating a lower GL/GI diet will reduce the change of getting diabetes.

so are you saying that your analysis is that women predisposed to t2 diabetes should eat high carb, high GL/GI diets, because there’s no evidence they shouldn’t?


ok- i think i get it. the study is just showing associations and not teasing out any mechanisms. further interventional studies would have to be done, not just observational ones. i do interventions on myself all the time and can see clearly that a low carb diet keeps me with normal blood sugar ranges (so far), and that a typical SAD diet puts me into the diabetic range easily.

Thanks for being patient, Brian!!

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