Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials

Adrian I Cozma, John L Sievenpiper, Russell J de Souza, Laura Chiavaroli, Vanessa Ha, D David Wang, Arash Mirrahimi, Matt E Yu, Amanda J Carleton, Marco Di Buono, Alexandra L Jenkins, Lawrence A Leiter, Thomas M S Wolever, Joseph Beyene, Cyril W C Kendall, David J A Jenkins, Adrian I Cozma, John L Sievenpiper, Russell J de Souza, Laura Chiavaroli, Vanessa Ha, D David Wang, Arash Mirrahimi, Matt E Yu, Amanda J Carleton, Marco Di Buono, Alexandra L Jenkins, Lawrence A Leiter, Thomas M S Wolever, Joseph Beyene, Cyril W C Kendall, David J A Jenkins

Abstract

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 (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) 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 (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). 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.

Trial registration: ClinicalTrials.gov NCT01363791.

Figures

Figure 1
Figure 1
Flowchart of literature search for the effect of fructose on glycemic end points (fasting glucose, fasting insulin, and glycated blood proteins [HbA1c and glycated albumin]). Electronic searches of Cochrane Library, EMBASE and MEDLINE databases were supplemented by manual searches of the references of included trials. DM 1, type 1 diabetes; DM 2, type 2 diabetes; DM 1/2, both type 1 and type 2 diabetes.
Figure 2
Figure 2
Forest plot of controlled feeding trials investigating the effect of isocaloric exchange of fructose for other carbohydrate on (A) glycated blood proteins (HbA1c and glycated albumin), (B) fasting glucose, and (C) fasting insulin. Data are SMD for glycated blood proteins and MD for fasting glucose and insulin with 95% CI (16). P values are for generic inverse variance random effects models. Interstudy heterogeneity was tested by the Cochran Q statistic (χ2) at a significance level of P < 0.1 and quantified by I2 (2,16). There were no studies investigating type 1 or undifferentiated diabetes for fasting insulin. CHO, carbohydrate. (A high-quality color representation of this figure is available in the online issue.)
Figure 2
Figure 2
Forest plot of controlled feeding trials investigating the effect of isocaloric exchange of fructose for other carbohydrate on (A) glycated blood proteins (HbA1c and glycated albumin), (B) fasting glucose, and (C) fasting insulin. Data are SMD for glycated blood proteins and MD for fasting glucose and insulin with 95% CI (16). P values are for generic inverse variance random effects models. Interstudy heterogeneity was tested by the Cochran Q statistic (χ2) at a significance level of P < 0.1 and quantified by I2 (2,16). There were no studies investigating type 1 or undifferentiated diabetes for fasting insulin. CHO, carbohydrate. (A high-quality color representation of this figure is available in the online issue.)
Figure 2
Figure 2
Forest plot of controlled feeding trials investigating the effect of isocaloric exchange of fructose for other carbohydrate on (A) glycated blood proteins (HbA1c and glycated albumin), (B) fasting glucose, and (C) fasting insulin. Data are SMD for glycated blood proteins and MD for fasting glucose and insulin with 95% CI (16). P values are for generic inverse variance random effects models. Interstudy heterogeneity was tested by the Cochran Q statistic (χ2) at a significance level of P < 0.1 and quantified by I2 (2,16). There were no studies investigating type 1 or undifferentiated diabetes for fasting insulin. CHO, carbohydrate. (A high-quality color representation of this figure is available in the online issue.)

References

    1. World Health Organization. The World Health Report 1998: Life in the 21st Century: A Vision for All Geneva, World Health Organization, 1998
    1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32:S1–S201
    1. Giovannucci E, Rimm EB, Liu Y, Willett WC. Height, predictors of C-peptide and cancer risk in men. Int J Epidemiol 2004;33:217–225
    1. Marriott BP, Cole N, Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J Nutr 2009;139:1228S–1235S
    1. Park YK, Yetley EA. Intakes and food sources of fructose in the United States. Am J Clin Nutr 1993;58(Suppl):737S–747S
    1. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004;79:537–543
    1. Bantle JP, Wylie-Rosett J, Albright AL, et al. American Diabetes Association Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care 2008;31(Suppl. 1):S61–S78
    1. Mann JI, De Leeuw I, Hermansen K, et al. Diabetes and Nutrition Study Group (DNSG) of the European Association Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis 2004;14:373–394
    1. Malerbi DA, Paiva ES, Duarte AL, Wajchenberg BL. Metabolic effects of dietary sucrose and fructose in type II diabetic subjects. Diabetes Care 1996;19:1249–1256
    1. Osei K, Bossetti B. Dietary fructose as a natural sweetener in poorly controlled type 2 diabetes: a 12-month crossover study of effects on glucose, lipoprotein and apolipoprotein metabolism. Diabet Med 1989;6:506–511
    1. Osei K, Falko J, Bossetti BM, Holland GC. Metabolic effects of fructose as a natural sweetener in the physiologic meals of ambulatory obese patients with type II diabetes. Am J Med 1987;83:249–255
    1. Anderson JW, Story LJ, Zettwoch NC, Gustafson NJ, Jefferson BS. Metabolic effects of fructose supplementation in diabetic individuals. Diabetes Care 1989;12:337–344
    1. Koivisto VA, Yki-Järvinen H. Fructose and insulin sensitivity in patients with type 2 diabetes. J Intern Med 1993;233:145–153
    1. Blayo A, Fontveille AM, Rizkalla S, Bruzzo F, Slama G. Effets metaboliques de la consommation quotidienne pendant un an de saccharose ou de fructose par des diabetiques. Médecine et Nutrition 1990;26:909–913 [in French]
    1. Bantle JP, Laine DC, Thomas JW. Metabolic effects of dietary fructose and sucrose in types I and II diabetic subjects. JAMA 1986;256:3241–3246
    1. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 510. Oxford, UK, Cochrane Collaboration, 2011. Available from . Accessed on 15 May 2012
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
    1. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001;286:944–953
    1. Elbourne DR, Altman DG, Higgins JPT, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol 2002;31:140–149
    1. Bantle JP, Swanson JE, Thomas W, Laine DC. Metabolic effects of dietary fructose in diabetic subjects. Diabetes Care 1992;15:1468–1476
    1. Grigoresco C, Rizkalla SW, Halfon P, et al. Lack of detectable deleterious effects on metabolic control of daily fructose ingestion for 2 mo in NIDDM patients. Diabetes Care 1988;11:546–550
    1. Thorburn AW, Crapo PA, Griver K, Wallace P, Henry RR. Long-term effects of dietary fructose on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. Metabolism 1990;39:58–63
    1. Vaisman N, Niv E, Izkhakov Y. Catalytic amounts of fructose may improve glucose tolerance in subjects with uncontrolled non-insulin-dependent diabetes. Clin Nutr 2006;25:617–621
    1. Pelkonen R, Aro A, Nikkilä EA. Metabolic effects of dietary fructose in insulin dependent diabetes of adults. Acta Med Scand Suppl 1972;542:187–193
    1. Turner JL, Bierman EL, Brunzell JD, Chait A. Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men. Am J Clin Nutr 1979;32:1043–1050
    1. Crapo PA, Kolterman OG, Henry RR. Metabolic consequence of two-week fructose feeding in diabetic subjects. Diabetes Care 1986;9:111–119
    1. McAteer EJ, O’Reilly G, Hadden DR. The effects of one month high fructose intake on plasma glucose and lipid levels in non-insulin-dependent diabetes. Diabet Med 1987;4:62–64
    1. Thorburn AW, Crapo PA, Beltz WF, Wallace P, Witztum JL, Henry RR. Lipid metabolism in non-insulin-dependent diabetes: effects of long-term treatment with fructose-supplemented mixed meals. Am J Clin Nutr 1989;50:1015–1022
    1. Center for Drug Evaluation and Research Guidance for Industry: Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention (DRAFT GUIDANCE). Rockville, Md, U.S. Department of Health and Human Services Food and Drug Administration, 2008, p. 1–30
    1. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360–372
    1. Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr 2008;88:1419–1437
    1. Jones IR, Owens DR, Williams S, et al. Glycosylated serum albumin: an intermediate index of diabetic control. Diabetes Care 1983;6:501–503
    1. Sievenpiper JL, Carleton AJ, Chatha S, et al. Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans. Diabetes Care 2009;32:1930–1937
    1. Atkinson FS, Foster-Powell K, Brand-Miller JC. International tables of glycemic index and glycemic load values: 2008. Diabetes Care 2008;31:2281–2283
    1. Thomas DE, Elliott EJ. The use of low-glycaemic index diets in diabetes control. Br J Nutr 2010;104:797–802
    1. Hawkins M, Gabriely I, Wozniak R, Vilcu C, Shamoon H, Rossetti L. Fructose improves the ability of hyperglycemia per se to regulate glucose production in type 2 diabetes. Diabetes 2002;51:606–614
    1. Petersen KF, Laurent D, Yu C, Cline GW, Shulman GI. Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans. Diabetes 2001;50:1263–1268
    1. Rech ME. Observations on the decay of glycated hemoglobin HbA1c in diabetic patients. Exp Clin Endocrinol Diabetes 1996;104:102–105
    1. Cozma AI, Sievenpiper JL, Chiavaroli L, et al. Effect of fructose on glycemic control in diabetes: a meta-analysis of controlled feeding trials. Can J Diabetes 2011;35:420–421

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