Effect of Fructose on Glycemic Control in Diabetes A systematic review and meta-analysis of controlled feeding trials

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% Cl for glycated hemoglobin (HbA(1c)) and glycatecl 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% Cl -0.46 to -0.04]; P = 0.02) with significant intertrial heterogeneity (I-2 = 63%; P = 0.001). This reduction is equivalent to a similar to 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. Diabetes Care 35:1611-1620, 2012