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Epidemiology and Population Health

Personalized nutrition: pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low-carbohydrate versus low-fat diet



The interaction between fasting plasma glucose (FPG) and fasting insulin (FI) concentrations and diets with different carbohydrate content were studied as prognostic markers of weight loss as recent studies up to 6 months of duration have suggested the importance of these biomarkers.


This was a retrospective analysis of a clinical trial where participants with obesity were randomized to an ad libitum low-carbohydrate diet or a low-fat diet with low energy content (1200–1800 kcal/day [≈ 5.0–7.5 MJ/d]; ≤ 30% calories from fat) for 24 months. Participants were categorized (pretreatment) as normoglycemic (FPG < 5.6 mmol/L) or prediabetic (FPG ≥ 5.6–6.9 mmol/L) and further stratified by median FI. Linear mixed models were used to examine outcomes by FPG and FI values.


After 2 years, participants with prediabetes and high FI lost 7.2  kg (95% CI 2.1;12.2, P = 0.005) more with the low-fat than low-carbohydrate diet, whereas those with prediabetes and low FI tended to lose 6.2  kg (95% CI −0.9;13.3, P = 0.088) more on the low-carbohydrate diet than low-fat diet [mean difference: 13.3 kg (95% CI 4.6;22.0, P = 0.003)]. No differences between diets were found among participants with normoglycemia and either high or low FI (both P ≥ 0.16).


Fasting plasma glucose and insulin are strong predictors of the weight loss response to diets with different macronutrient composition and might be a useful approach for personalized weight management.

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Author contributions

GDF, HRW, JOH, and SK conceived and carried out the original experiments. MFH, YZ, and AA conceived the idea of the current analysis. BWP performed insulin sensitivity analyses. MFH analyzed the data and wrote the first draft of the paper. All authors have reviewed the manuscript critically and approved the final manuscript.


The original study was supported by the National Institutes of Health, and the reanalysis reported in this manuscript was funded by grants from Gelesis Inc.

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Corresponding author

Correspondence to Mads F. Hjorth.

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Conflict of interest

MFH, YZ, and AA are co-inventers on a pending provisional patent application on the use of biomarkers for prediction of weight loss responses. AA is co-inventor of other related patents/patent applications owned by UCPH, in accordance with Danish law. AA and JOH are consultants for Gelesis Inc. concerning scientific advice unrelated to the current paper. AA is furthermore consultant/member of advisory boards for Groupe Éthique et Santé, France, Nestlé Research Center, Switzerland, Weight Watchers, USA, BioCare Copenhagen, Zaluvida, Switzerland, Basic Research, USA, Novo Nordisk, Denmark, & Saniona, Denmark. MFH & AA are co-authors of the book “Spis dig slank efter dit blodsukker” (Eat according to your blood sugar and be slim)/Politikens Forlag, Denmark, and of other books about personalized nutrition for weight loss. AA is co-owner and member of the Board of the consultancy company Dentacom Aps, Denmark, & co-founder and co-owner of UCPH spin-out Mobile Fitness A/S, Flaxslim ApS. MFH and AA are co-founder and co-owner of UCPH spin-out Personalized Weight Management 'Research Consortium ApS ( SK is a shareholder of Aspire Bariatrics, receives research support from Johnson & Johnson and Merck, and has served as a consultant for Pfizer and Jannsen.

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Hjorth, M.F., Astrup, A., Zohar, Y. et al. Personalized nutrition: pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low-carbohydrate versus low-fat diet. Int J Obes 43, 2037–2044 (2019).

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