Review of Fructose on Insulin Sensitivity in Non-Diabetic Subjects

A new systematic review and meta-analysis examining the effects of fructose on insulin sensitivity in non-diabetic subjects was published in the American Journal of Clinical Nutrition. Researchers specifically looked at controlled clinical trials with normal weight, overweight, and obese non-diabetic participants. All studies used in the analysis were assessed and provided a Heyland methodological quality score with scores greater than or equal to 8 considered to be of high quality. Researchers sorted the data to look separately at energy-matched (isocaloric) and hypercaloric trials. Researchers identified 32 energy-matched and 14 hypercaloric comparisons.

All participants were between the ages of 22 and 54 years old. In energy-matched comparison, the genders were represented equally, whereas in the hypercaloric trials, women were greatly outnumbered by men, comprising only 18% of the participants. In these studies, fructose was provided in the form of beverage, food or as crystalline fructose. For all hypercaloric studies, fructose was provided in a mean dietary caloric surplus of 18% to 33% of total energy intake. Of the energy-matched studies, 34% received a high quality score where as 43% of the hypercaloric studies received a high quality score.

When examining the effect of fructose on plasma insulin, isocaloric fructose intake resulted in elevated fasting insulin concentrations in overweight and obese individuals only. When fructose was taken hypercalorically, fasting insulin was elevated only in subjects who were off spring of type 2 diabetics (OffT2D); normal weight, overweight and obese individuals did not demonstrate a change in fasting insulin. When looking at the data for homeostatic model assessment for insulin resistance (HOMA-IR), the meta-analysis shows that isocaloric fructose intake resulted in an increase in HOMA-IR in the overweight and obese group only. For the hypercaloric trials, HOMA-IR was elevated in the OffT2D group only. Researchers also looked at insulin-stimulated glucose disposal rates which demonstrated that fructose intake in both isocaloric and hypercaloric trials had no effect. Lastly, researchers looked at hepatic insulin sensitivity. In normal weight individuals, both isocaloric and hypercaloric fructose intake resulted in hepatic insulin resistance. Hypercaloric fructose intake also resulted in hepatic insulin resistance for OffT2D participants. Researchers did not provide any data on hepatic insulin resistance in overweight or obese individuals.

Researchers concluded “that both isocaloric fructose consumption and hypercaloric fructose consumption induce hepatic insulin resistance in normal-weight, nondiabetic adults. Short- and medium-term fructose consumption does not promote muscle or peripheral insulin resistance as was shown by a lack of a change in insulin-stimulated glucose disposal in all analyses. In addition, the energy-matched (isocaloric) substitution of dietary carbohydrates for fructose had no effect on fasting insulin concentrations and the HOMA-IR, whereas hypercaloric fructose supplementation raised fasting insulin concentrations and the HOMA-IR on OffT2D subjects but not in normal-weight and overweight or obese participants.”