Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes

Metabolism. 2015 Feb;64(2):253-62. doi: 10.1016/j.metabol.2014.10.004. Epub 2014 Oct 8.


Objective: Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet.

Research design: Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used.

Methods: Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat.

Results: The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged.

Conclusions: Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed.

Trial registration: NCT01469104.

Keywords: Carbohydrate; Circadian rhythm; Diabetes; Diet; Fasting.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • C-Peptide / blood
  • Caloric Restriction*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diet, Carbohydrate-Restricted*
  • Diet, Reducing
  • Fasting*
  • Glucagon / blood*
  • Hospitals, Veterans
  • Humans
  • Hyperglycemia / prevention & control*
  • Insulin / blood*
  • Male
  • Middle Aged
  • Weight Loss


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucagon

Associated data