Effect of Fructose on Glycemic Control in Diabetes
A systematic review and meta-analysis of controlled feeding trials
- Adrian I. Cozma, HBSC1,2,
- John L. Sievenpiper, MD, PHD1,3⇓,
- Russell J. de Souza, SCD, RD1,2,4,
- Laura Chiavaroli, MSC1,2,
- Vanessa Ha, HBSC1,2,
- D. David Wang, HBSC1,2,
- Arash Mirrahimi, MSC1,2,
- Matt E. Yu, HBSC1,2,
- Amanda J. Carleton, MSC1,5,
- Marco Di Buono, PHD6,
- Alexandra L. Jenkins, PHD, RD1,
- Lawrence A. Leiter, MD1,2,7,8,
- Thomas M.S. Wolever, MD, PHD1,2,7,8,
- Joseph Beyene, PHD9,10,11,
- Cyril W.C. Kendall, PHD1,2,12 and
- David J.A. Jenkins, MD, PHD1,2,7,8
- 1Clinical Nutrition and Risk Factor Modification Center, St. Michael’s Hospital, Toronto, Ontario, Canada
- 2Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 3Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
- 4Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 5Undergraduate Medical Education (MD Program), Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 6Heart and Stroke Foundation of Ontario, Toronto, Ontario, Canada
- 7Division of Endocrinology, St. Michael’s Hospital, Toronto, Ontario, Canada
- 8Keenan Research Center of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
- 9Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- 10Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
- 11Child Health Evaluative Sciences (CHES), The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
- 12College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
- Corresponding author: John L. Sievenpiper,
OBJECTIVE The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes.
RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA1c) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic. Trial quality was assessed by the Heyland methodological quality score (MQS).
RESULTS Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD −0.25 [95% CI −0.46 to −0.04]; P = 0.02) with significant intertrial heterogeneity (I2 = 63%; P = 0.001). This reduction is equivalent to a ∼0.53% reduction in HbA1c. Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point.
CONCLUSIONS Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required.
- Received January 11, 2012.
- Accepted February 15, 2012.
- © 2012 by the American Diabetes Association.
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