Mice fed high fat diets, forced to fast, and then killed to study diabetes in humans – but results differ from human studies

Lamont, Waters & Andrikopoulos 2016, ‘A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice’, Nutrition & Diabetes, 6, 194.

Institution: Department of Medicine, Austin Hospital, The University of Melbourne


The study aimed at discovering whether a high-fat, low carbohydrate diet could act as a management or prevention option for people with type-2 diabetes.

The Experiment

The experimental period commenced when mice were 6 weeks old, where they were assigned into two experimental groups, one that was fed a normal diet, the other was fed the high fat, low carbohydrate diet. The mice were subjected to weekly blood sampling and weighing with the addition of a fasting period and two glucose tolerance tests.

fasting period of 16 hours was implemented after 6 weeks of the experiment with additional blood sampling taken prior to fasting, after fasting period, and after re-introduction of food. The first glucose tolerance test was performed on awake mice in week 7 with three blood samples being taken over a period of 30 minutes after glucose was forcibly consumed through a tube. The second glucose tolerance test was performed on week 9 of the experiment with six blood samples being taken over a 30-minute period after an injection of glucose into the blood. After this test mice were immediately killed at 15 weeks of age using an overdose of sodium pentobarbital for tissue sample collection.


The diabetic prone mice that were fed the high fat, low carbohydrate diet gained weight faster and were more resistant to insulin compared to the diabetic prone mice that were fed normal feed. Overall mice that were fed this diet had a lower glucose tolerance.


The study concluded that there were no long-term benefits in diabetes management through the implementation of a high fat, low carb diet.

Appropriate Human Model?

The article makes reference to a number of studies (seen below) that show weight loss and potential diabetic benefits from low carbohydrate diets in humans. It was due to the results in these articles that the study in question was performed, however, the study chose mice as their species subject. The study involving mice came up with contrasting results compared to the human studies and therefore this calls into question the relevance of mice being used in this scientific area. The low carbohydrate diet clearly has a different effect on humans compared to mice.

A non-exhaustive list of human studies that showed some positive results in this area of study:


  • Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003; 348: 2082–2090.
  • Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr 2009; 90: 23–32.
  • Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003; 348: 2074–2081.
  • Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008; 359: 229–241.
  • Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015; 31: 1–13.
  • Gannon MC, Nuttall FQ. Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 2004; 53: 2375–2382.
  • Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition 2012; 28: 1016–1021.



This experiment was funded by the National Health and Medical Research Council.

What Can You Do?

Please write to the following to voice your concerns about the approval of research. Ask how they justify the use of animals in experimental procedures when these animals do not appropriately model humans and in fact give contrasting results.

Vice Chancellor, University of Melbourne

Email :vc@unimelb.edu.au

Chair, Animal Ethics Committee
University of Melbourne
Level 5, Alan Gilbert Building
161 Barry Street
Melbourne 3010
Email: animal-ethics@unimelb.edu.au

Professor Paul Johnson
Director of Research Austin Life Sciences
Email: paul.johnson@austin.org.au


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