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Glossary

Thrifty genotype hypothesis

Defined in topic 13

James Neel's 1962 proposal that genes favoring efficient fat storage were selected by famine and turned harmful with plenty. Famine comparisons and most selection scans go against it, though a Samoan variant of CREBRF is a real exception, and a 2024 review calls the question unresolved.

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Where this comes from

In the reference topic that owns this term

Reference topic 13, The Thrifty Body, states the mismatch as a card: what the system evolved to expect, what it gets instead, and what happens in the gap.

Mismatch card

What it expects

Food that takes work to get, lean seasons, fiber-rich plants and hours of physical work.

What it gets

Cheap, energy-dense, ultra-processed food all day, little physical work and short sleep.

What happens in the gap

Fat accumulates, a body built to defend its stores resists losing it, and fat that overflows into liver, muscle and pancreas is thought to drive insulin resistance and type 2 diabetes.

The full card, and the topic behind it

What that chapter recommends

3 of the 7 graded recommendations in Reference topic 13, strongest evidence first. How the grades work.

  1. Move for insulin sensitivity, not to burn off food

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.

    Aim for 150-300 minutes a week of moderate activity plus resistance training on two or three non-consecutive days. A session can improve insulin sensitivity for 2 to 72 hours, so avoid more than two days off in a row.

    Read it in full

  2. Act early

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.

    With prediabetes, a program aiming at 7% weight loss and 150 minutes of weekly activity cut diabetes incidence by 58% over about three years.

    Read it in full

  3. Treat GLP-1 drugs as a legitimate medical option

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.

    chosen with a clinician and planned as long-term treatment, since weight usually returns after stopping. The trials enrolled adults with a BMI of 30 or more (27 with a weight-related condition).

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Related terms

The argument behind this term, its studies and its notes are in Reference topic 13 of the reference library. The book gives the practical version. Get the book.