Consuming glucose-sweetened, not fructose-sweetened, beverages increases fasting insulin in healthy humans

Eur J Clin Nutr 2018 Aug 11; // — Kuzma JN, Comer G, Hagman DK, et al. — Download Research Study PDF — 


  • To conduct a secondary analysis to determine whether consuming beverages sweetened with fructose vs. HFCS vs. glucose differentially affected fasting glucose, insulin, and the homeostasis model assessment index of insulin resistance (HOMA-IR).


  • When consumed with a solid food diet in caloric excess, fructose-sweetened, but not glucose-sweetened, beverages promote hepatic de novo lipogenesis (DNL), ectopic fat deposition, dyslipidemia, and insulin resistance compared to glucose-sweetened beverages.
  • It is not clear, however, whether the insulin resistance is due to the greater increase in overall fat mass that results from long-term consumption of fructose-sweetened beverages, or whether fructose acutely triggers insulin resistance through mechanisms that are independent of changes in fat mass.


  • The authors conducted a double-blinded, randomized, three-phase cross-over study, which included a total of 24 subjects, ages 18-65 with a body mass index (BMI) 20–40 kg/m2.
  • Each participant completed three 8-day dietary intervention periods during which subjects were provided with 150% of their estimated energy requirements: 25% of energy from sweetened beverages (glucose, HFCS, and fructose, in random order), and 125% as identical solid foods.
  • Participants were asked to drink all four servings of the SSB every day, and to consume the provided solid foods ad libitum, i.e., to eat only to satiety and return all leftover foods for weigh-backs.
  • Subjects were asked to maintain their normal physical activity pattern across the entire study period (~2.5 months), which was assessed by modified Blair Physical Activity Questionnaires.


  • There was no effect of diet on day 9 fasting concentrations of glucose, insulin, or HOMA-IR.
  • Fasting insulin was lowest at the end of the fructose phase, followed by the HFCS phase, and was highest after the glucose phase (p = 0.042).
  • In normal weight subjects, mean fasting insulin and HOMA-IR values were lowest following the fructose period, followed by the HFCS period, and were highest following the glucose-beverage period. This trend was not observed in overweight/obese subjects.


  • In this study, there was no evidence that the consumption of excessive amounts of fructose from SSB differentially increases insulin resistance compared to SSB sweetened with HFCS or glucose.
  • However, in the short-term, higher glucose content of the beverages was significantly related to higher fasting insulin and HOMA-IR in a concentration-dependent manner.

Points to Consider

  • The current study included a rather small sample and was relatively short-term. Long-term effects will have to be determined in larger randomized studies with a longer duration and follow-up.