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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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  1. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63:2985–3023.

    Article  Google Scholar 

  2. Cornier M, Donahoo WT, Pereira R, Gurevich I, Westergren R, Enerback S, et al. Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women. Obes Res. 2005;13:703–9.

    Article  CAS  Google Scholar 

  3. Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, et al. A low-glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial. Diabetes Care. 2005;28:2939–41.

    Article  Google Scholar 

  4. Gardner CD, Offringa LC, Hartle JC, Kapphahn K, Cherin R. Weight loss on low‐fat vs. low‐carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: a randomized pilot trial. Obesity . 2016;24:79–86.

    Article  CAS  Google Scholar 

  5. McClain AD, Otten JJ, Hekler EB, Gardner CD. Adherence to a low‐fat vs. low‐carbohydrate diet differs by insulin resistance status. Diabetes, Obes Metab. 2013;15:87–90.

    Article  CAS  Google Scholar 

  6. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a low–glycemic load vs low-fat diet in obese young adults: a randomized trial. JAMA. 2007;297:2092–102.

    Article  CAS  Google Scholar 

  7. Hjorth MF, Ritz C, Blaak EE, Saris WH, Langin D, Poulsen SK, et al. Pretreatment fasting plasma glucose and insulin modify dietary weight loss success: results from 3 randomized clinical trials. Am J Clin Nutr. 2017;106:499–505.

    Article  CAS  Google Scholar 

  8. Hjorth MF, Due A, Larsen TM, Astrup A. Pre-treatment fasting plasma glucose modifies dietary weight loss maintenance success: results from a stratified RCT. Obesity. 2017;25:2045–8.

    Article  CAS  Google Scholar 

  9. Foster GD, Wyatt HR, Hill JO, Makris AP, Rosenbaum DL, Brill C, et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med. 2010;153:147–57.

    Article  Google Scholar 

  10. Atkins RC. Dr. Atkins’ New Diet Revolution. New York: Avon Books; 1998.

  11. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther. 2003;5:1003–15.

    Article  CAS  Google Scholar 

  12. Ballesteros-Pomar MD, Calleja-Fernandez AR, Vidal-Casariego A, Urioste-Fondo AM, Cano-Rodríguez I. Effectiveness of energy-restricted diets with different protein: carbohydrate ratios: the relationship to insulin sensitivity. Public Health Nutr. 2010;13:2119–26.

    Article  Google Scholar 

  13. Shyam S, Arshad F, Ghani RA, Wahab NA, Safii NS, Nisak MYB, et al. Low glycaemic index diets improve glucose tolerance and body weight in women with previous history of gestational diabetes: a six months randomized trial. Nutr J. 2013;12:68.

    Article  CAS  Google Scholar 

  14. Ghani RA, Shyam S, Arshad F, Wahab NA, Chinna K, Safii NS, et al. The influence of fasting insulin level in post-gestational diabetes mellitus women receiving low-glycaemic-index diets. Nutr Diabetes. 2014;4:e107.

    Article  CAS  Google Scholar 

  15. Kong LC, Wuillemin PH, Bastard JP, Sokolovska N, Gougis S, Fellahi S, et al. Insulin resistance and inflammation predict kinetic body weight changes in response to dietary weight loss and maintenance in overweight and obese subjects by using a Bayesian network approach. Am J Clin Nutr. 2013;98:1385–94.

    Article  CAS  Google Scholar 

  16. Hwang JJ, Jiang L, Hamza M, Rangel ES, Dai F, Belfort-DeAguiar R, et al. Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI insight. 2017;2:e95913.

  17. Schroeder BO, Bäckhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22:1079–89.

    Article  CAS  Google Scholar 

  18. Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci Rep. 2017;7:2594.

    Google Scholar 

  19. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 2015;22:971–82.

    Article  CAS  Google Scholar 

  20. Hjorth MF, Roager HM, Larsen TM, Poulsen SK, Licht TR, Bahl MI, et al. Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. Int J Obes. 2018;42:580–583.

  21. Hjorth MF, Blædel T, Bendtsen LQ, Lorenzen JK, Holm JB, Kiilerich P, et al. Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis. Int J Obes. 2018.

  22. Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr. 2006;83:1025–31.

    Article  CAS  Google Scholar 

  23. Brownlee IA, Chater PI, Pearson JP, Wilcox MD. Dietary fibre and weight loss: Where are we now? Food Hydrocoll. 2017;68:186–191. 

  24. Roager HM, Vogt JK, Kristensen M, Hansen LBS, Ibrügger S, Mærkedahl RB, et al. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial. Gut 2017.

  25. Poulsen SK, Due A, Jordy AB, Kiens B, Stark KD, Stender S, et al. Health effect of the New Nordic Diet in adults with increased waist circumference: a 6-mo randomized controlled trial. Am J Clin Nutr. 2014;99:35–45.

    Article  CAS  Google Scholar 

  26. Pereira MA, Swain J, Goldfine AB, Rifai N, Ludwig DS. Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss. JAMA. 2004;292:2482–90.

    Article  CAS  Google Scholar 

  27. Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, et al. Calorie for calorie, dietary fat restriction results in more body fat loss than carbohydrate restriction in people with obesity. Cell Metab. 2015;22:427–36.

    Article  CAS  Google Scholar 

  28. Hjorth MF, Zohar Y, Hill JO, Astrup A. Personalized dietary management of overweight and obesity based on measures of insulin and glucose. Annu Rev Nutr. 2018;38:19.1–19.28.

    Article  Google Scholar 

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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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Correspondence to Mads F. Hjorth.

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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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