Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity

Michael Scally MD

Doctor of Medicine
10+ Year Member
[OA] Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity

BACKGROUND: A fundamental precept of the carbohydrate–insulin model of obesity is that insulin secretion drives weight gain. However, fasting hyperinsulinemia can also be driven by obesity-induced insulin resistance. We used genetic variation to isolate and estimate the potentially causal effect of insulin secretion on body weight.

METHODS: Genetic instruments of variation of insulin secretion [assessed as insulin concentration 30 min after oral glucose (insulin-30)] were used to estimate the causal relationship between increased insulin secretion and body mass index (BMI), using bidirectional Mendelian randomization analysis of genome-wide association studies.

Data sources included summary results from the largest published metaanalyses of predominantly European ancestry for insulin secretion (n = 26037) and BMI (n = 322154), as well as individual-level data from the UK Biobank (n = 138541). Data from the Cardiology and Metabolic Patient Cohort study at Massachusetts General Hospital (n = 1675) were used to validate genetic associations with insulin secretion and to test the observational association of insulin secretion and BMI.

RESULTS: Higher genetically determined insulin-30 was strongly associated with higher BMI (β = 0.098, P = 2.2 × 10−21), consistent with a causal role in obesity. Similar positive associations were noted in sensitivity analyses using other genetic variants as instrumental variables. By contrast, higher genetically determined BMI was not associated with insulin-30.

CONCLUSIONS: Mendelian randomization analyses provide evidence for a causal relationship of glucose-stimulated insulin secretion on body weight, consistent with the carbohydrate–insulin model of obesity.

Astley CM, Todd JN, Salem RM, et al. Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity. Clinical Chemistry 2018;64:192. Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity
 
Good old Ludwig. Continuing to ignore direct research that killed this hypothesis long ago in favor of theoretical masturbation.

Tiny effect size, focusing on BMI, conveniently ignoring other Mendelian randomization studies that show that obesity causes insulin problems, NOT the other way round, etc. ,etc.

I mean come on man - this isn't even good theoretical masturbation, it's desperate "I must use statistical magic to find SOMETHING to support my beliefs, ANYTHING at all" masturbation.
 

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