Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Effects of a short-term overfeeding with fructose or glucose in healthy young males. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. The Effect of Normally Consumed Amounts of Sucrose or High Fructose Corn Syrup on Lipid Profiles, Body Composition and Related Parameters in Overweight/Obese Subjects Simultaneous ingestion of fructose and fat exacerbates postprandial exogenous lipidemia in young healthy Japanese women. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men Fructose ingestion acutely elevates blood pressure in healthy young humans. The Effects of Physiologic Amounts of Simple Sugars on Lipoprotein, Glucose, and Insulin Levels in Normal Subjects The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters Effects of pure sugar vs. mixed starch fructose loads on food intake The effects of glucose, fructose, and sucrose ingestion during exercise. A prospective study of sugar intake and risk of type 2 diabetes in women.
Significance Fructose compared with glucose may be a weaker suppressor of appetite . Here we sought to determine the effects of fructose versus glucose on brain , hormone , and appetitive responses to food cues and food-approach behavior . We show that the ingestion of fructose compared with glucose result ed in smaller increases in plasma insulin levels and greater brain responses to food cues in the visual cortex and left orbital frontal cortex . Ingestion of fructose versus glucose also led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods . These findings suggest that ingestion of fructose relative to glucose activates brain regions involved in attention and reward processing and may promote feeding behavior . Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite , and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state . We sought to determine the effects of ingesting fructose versus glucose on brain , hormone , and appetitive responses to food cues and food-approach behavior . Twenty-four healthy volunteers underwent two functional magnetic resonance imaging ( fMRI ) sessions with ingestion of either fructose or glucose in a double-blinded , r and om-order cross-over design . fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design . After each block , participants rated hunger and desire for food . Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses . Hormones were measured at baseline and 30 and 60 min after drink ingestion . Ingestion of fructose relative to glucose result ed in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex ( in whole-brain analysis ) and left orbital frontal cortex ( in region-of-interest analysis ) . Parallel to the neuroimaging findings , fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods . These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior An increasing amount of fructose in the diet is suggested to play a causal role in the pathogenesis of the metabolic syndrome , type 2 diabetes and fatty liver . Our aim was to investigate and compare the effects of very high fructose and very high glucose in hyperenergetic diets on glucose and lipid metabolism and on fat depots in healthy humans . We conducted an exploratory , prospect i ve , r and omised , single-blinded , intervention trial . Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks . Insulin sensitivity was estimated from oral glucose tolerance tests . Visceral and subcutaneous abdominal fat was determined with MRI . Liver fat and intramyocellular lipids of the tibialis anterior muscle were measured with (1)H magnetic resonance spectroscopy . A total of twenty healthy subjects ( fructose group n 10 and glucose group n 10 ; twelve males and eight females ) completed the study . They had a mean age of 30·5 ( SEM 2·0 ) years and a mean BMI of 25·9 ( SEM 0·5 ) kg/m(2 ) . Insulin sensitivity appeared to decrease both in the fructose and glucose groups . TAG markedly increased in the fructose group . No strong alterations or treatment effects were found for liver fat , visceral fat , subcutaneous abdominal fat and intramyocellular lipids of the tibialis anterior muscle . In conclusion , the effects of very high fructose and very high glucose in hyperenergetic diets on glucose metabolism and body fat composition were not different in the healthy participants of the present study . However , elevation of plasma TAG seemed to be fructose-specific Consumption of simple carbohydrates has markedly increased over the past decades , and may be involved in the increased prevalence in metabolic diseases . Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial . We therefore compared the effects of hypercaloric diets enriched with fructose ( HFrD ) or glucose ( HGlcD ) in healthy men . Eleven subjects were studied in a r and omised order after 7 d of the following diets : ( 1 ) weight maintenance , control diet ; ( 2 ) HFrD ( 3.5 g fructose/kg fat-free mass ( ffm ) per d , + 35 % energy intake ) ; ( 3 ) HGlcD ( 3.5 g glucose/kg ffm per d , + 35 % energy intake ) . Fasting hepatic glucose output ( HGO ) was measured with 6,6 - 2H2-glucose . Intrahepatocellular lipids ( IHCL ) and intramyocellular lipids ( IMCL ) were measured by 1H magnetic resonance spectroscopy . Both fructose and glucose increased fasting VLDL-TAG ( HFrD : + 59 % , P < 0.05 ; HGlcD : + 31 % , P = 0.11 ) and IHCL ( HFrD : + 52 % , P < 0.05 ; HGlcD : + 58 % , P = 0.06 ) . HGO increased after both diets ( HFrD : + 5 % , P < 0.05 ; HGlcD : + 5 % , P = 0.05 ) . No change was observed in fasting glycaemia , insulin and alanine aminotransferase concentrations . IMCL increased significantly only after the HGlcD ( HFrD : + 24 % , NS ; HGlcD : + 59 % , P < 0.05 ) . IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD , but were increased compared to values observed with a weight maintenance diet . However , glucose led to a higher increase in IMCL than fructose Intake of high-fructose corn syrup ( HFCS ) has been suggested to contribute to the increased prevalence of obesity , whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose . We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week , free-living period at these consumption levels . This was a r and omized , prospect i ve , double-blind , parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th , 50th , and 90th percentile population consumption of fructose ( the equivalent of 40 , 90 , or 150 g of sugar per day in a 2000-kcal diet ) . Before and after the 10-week intervention , 24-hour blood sample s were collected . The area under the curve ( AUC ) for glucose , insulin , leptin , active ghrelin , triglyceride , and uric acid was measured . There were no group differences at baseline or posttesting for all outcomes ( interaction , P > .05 ) . The AUC response of glucose , active ghrelin , and uric acid did not change between baseline and posttesting ( P > .05 ) , whereas the AUC response of insulin ( P < .05 ) , leptin ( P < .001 ) , and triglyceride ( P < .01 ) increased over the course of the intervention when the 6 groups were averaged . We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low , medium , and high levels of consumption Background Prospect i ve studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking . Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations , as well as liver enzyme ( AST , ALT , and GGT ) activities in men and women . Methods As part of a parallel arm study , older ( age 40–72 ) , overweight and obese male and female subjects ( BMI 25–35 kg/m2 ) consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 wks . Fasting and 24-h blood collection s were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid , RBP-4 and liver enzyme activities were measured . Results Consumption of fructose , but not glucose , led to significant increases of 24-h uric acid profiles ( P < 0.0001 ) and RBP-4 concentrations ( P = 0.012 ) , as well as plasma GGT activity ( P = 0.04 ) . Fasting plasma uric acid concentrations increased in both groups ; however , the response was significantly greater in subjects consuming fructose ( P = 0.002 for effect of sugar ) . Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women ( P = 0.024 ) . Conclusions These findings suggest that consumption of fructose at 25 % of energy requirements for 10 wks , compared with isocaloric consumption of glucose , may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid , GGT activity , suggesting alteration of hepatic function , and the production of RBP-4 Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones . Recent studies have begun to eluci date brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging ( MRI ) , but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear . In this paper , we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system . Using a cross-over , double-blind , placebo-controlled design , we compared resting state functional connectivity ( rsFC ) strengths within the basal ganglia/limbic network in 12 healthy lean males . Each subject was administered fructose , glucose and placebo on three separate occasions . Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite . Glucose ingestion induced significantly greater elevations in plasma glucose , insulin , GLP-1 and GIP , while feelings of fullness increased and prospect i ve food consumption decreased relative to fructose . Furthermore , glucose increased rsFC of the left caudatus and putamen , precuneus and lingual gyrus more than fructose , whereas within the basal ganglia/limbic network , fructose increased rsFC of the left amygdala , left hippocampus , right parahippocampus , orbitofrontal cortex and pre central gyrus more than glucose . Moreover , compared to fructose , the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin . Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network , which are probably mediated by different insulin levels . A larger study would be recommended in order to confirm these findings OBJECTIVE Fructose has been implicated in obesity , partly due to lack of insulin-mediated leptin stimulation and ghrelin suppression . Most work has examined effects of pure fructose , rather than high-fructose corn syrup ( HFCS ) , the most commonly consumed form of fructose . This study examined effects of beverages sweetened with HFCS or sucrose ( Suc ) , when consumed with mixed meals , on blood glucose , insulin , leptin , ghrelin , and appetite . METHODS Thirty lean women were studied on two r and omized 2-d visits during which HFCS- and Suc-sweetened beverages were consumed as 30 % of energy on isocaloric diets during day 1 while blood was sample d. On day 2 , food was eaten ad libitum . Subjects rated appetite at design ated times throughout visits . RESULTS No significant differences between the two sweeteners were seen in fasting plasma glucose , insulin , leptin , and ghrelin ( P > 0.05 ) . The within-day variation in all four items was not different between the two visits ( P > 0.05 ) . Net areas under the curve were similar for glucose , insulin , and leptin ( P > 0.05 ) . There were no differences in energy or macronutrient intake on day 2 . The only appetite variable that differed between sweeteners was desire to eat , which had a higher area under the curve the day after Suc compared with HFCS . CONCLUSION These short-term results suggest that , when fructose is consumed in the form of HFCS , the measured metabolic responses do not differ from Suc in lean women . Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals , males , or longer periods The American Heart Association ( AHA ) has advocated that women and men not consume more than 100 and 150 kcal/day , respectively , from added sugars . These levels are currently exceeded by over 90 % of the adult population in the United States . Few data exist on longer-term metabolic effects when sucrose and High Fructose Corn Syrup ( HFCS ) , the principal sources of added dietary sugars , are consumed at levels typical of the general population . Sixty five overweight and obese individuals were placed on a eucaloric ( weight stable ) diet for 10-weeks , which incorporated sucrose- or HFCS-sweetened , low-fat milk at 10 % or 20 % of calories in a r and omized , double-blinded study . All groups responded similarly ( interaction p > 0.05 ) . There was no change in body weight in any of the groups over the 10-week study , or in systolic or diastolic blood pressure . Likewise , there were no changes in total cholesterol , triglycerides , low-density lipoprotein ( LDL ) , or apolipoprotein B ( Apo B ) . We conclude that ( 1 ) when consumed as part of a eucaloric diet fructose — when given with glucose ( as normally consumed ) does not promote weight gain or an atherogenic lipid profile even when consumed at two to four times the level recently recommended by the AHA . ( 2 ) There were no differences between HFCS and sucrose on these parameters AIM To investigate the acute effects of the simultaneous ingestion of fructose and fat on postpr and ial lipoprotein metabolism in healthy young women . METHODS Nine young healthy Japanese women with a normal weight ( body mass index : 18.5≤- < 25 kg/m(2 ) ) , a normal ovarian cycle and an apolipoprotein E 3/3 phenotype were enrolled as participants and studied on four occasions . At each session , the subjects ingested one of four beverages containing either glucose or fructose ( 0.5 g/kg body weight each ) with or without OFTT cream ( 1 g/kg , 0.35 g/ kg as fat ) in a r and omized crossover design . Blood sample s were collected at baseline and at 0.5 , 1 , 2 , 4 and 6 hours after ingestion . RESULTS The ingestion of fructose combined with fat led to significantly higher rises in the serum triglyceride ( TG ) , remnant-like particle (RLP)-TG , remnant lipoprotein-cholesterol ( RemL-C ) and apolipoprotein B-48 ( apoB48 ) concentrations with delayed peaks compared with that observed following ingestion of the other three types of beverages . The incremental area under the curve (ΔAUC)-TG and ΔAUC-apoB48 were larger than those observed for the ingestion of fat only . The serum RLP-TG and apoB48 concentrations returned to the fasting levels ( 0 hours ) at the end of the test ( 6 hours ) following the ingestion of fat only ; however , these concentrations did not return to the fasting levels following the intake of fructose combined with fat . CONCLUSIONS These findings suggest a delay in the clearance of intestinal TG-rich lipoproteins , namely chylomicron and its remnant , following the ingestion of fructose combined with fat . The simultaneous ingestion of fructose and fat markedly enhances postpr and ial exogenous lipidemia in young healthy Japanese women IMPORTANCE Increases in fructose consumption have paralleled the increasing prevalence of obesity , and high-fructose diets are thought to promote weight gain and insulin resistance . Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion , and central administration of fructose provokes feeding in rodents , whereas central ly administered glucose promotes satiety . OBJECTIVE To study neurophysiological factors that might underlie associations between fructose consumption and weight gain . DESIGN , SETTING , AND PARTICIPANTS Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded , r and om-order , crossover design . MAIN OUTCOME MEASURES Relative changes in hypothalamic regional cerebral blood flow ( CBF ) after glucose or fructose ingestion . Secondary outcomes included whole-brain analyses to explore regional CBF changes , functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses , and hormone responses to fructose and glucose ingestion . RESULTS There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion ( -5.45 vs 2.84 mL/g per minute , respectively ; mean difference , 8.3 mL/g per minute [ 95 % CI of mean difference , 1.87 - 14.70 ] ; P = .01 ) . Glucose ingestion ( compared with baseline ) increased functional connectivity between the hypothalamus and the thalamus and striatum . Fructose  increased connectivity between the hypothalamus and thalamus but not the striatum . Regional CBF within the hypothalamus , thalamus , insula , anterior cingulate , and striatum ( appetite and reward regions ) was reduced after glucose ingestion compared with baseline ( P < .05 significance threshold , family-wise error [ FWE ] whole-brain corrected ) . In contrast , fructose  reduced regional CBF in the thalamus , hippocampus , posterior cingulate cortex , fusiform , and visual cortex ( P < .05 significance threshold , FWE whole-brain corrected ) . In whole-brain voxel-level analyses , there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons . Fructose vs glucose ingestion result ed in lower peak levels of serum glucose ( mean difference , 41.0 mg/dL [ 95 % CI , 27.7 - 54.5 ] ; P < .001 ) , insulin ( mean difference , 49.6 μU/mL [ 95 % CI , 38.2 - 61.1 ] ; P < .001 ) , and glucagon-like polypeptide 1 ( mean difference , 2.1 pmol/L [ 95 % CI , 0.9 - 3.2 ] ; P = .01 ) . CONCLUSION AND RELEVANCE In a series of exploratory analyses , consumption of fructose compared with glucose result ed in a distinct pattern of regional CBF and a smaller increase in systemic glucose , insulin , and glucagon-like polypeptide 1 levels OBJECTIVE Adverse effects of hypercaloric , high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly . The implication s of fructose in amounts close to usual daily consumption , however , have not been well studied . This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS Nine healthy , normal-weight male volunteers ( aged 21–25 years ) were studied in this double-blind , r and omized , cross-over trial . All subjects consumed four different sweetened beverages ( 600 mL/day ) for 3 weeks each : medium fructose ( MF ) at 40 g/day , and high fructose ( HF ) , high glucose ( HG ) , and high sucrose ( HS ) each at 80 g/day . Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production . Lipid profile , glucose , and insulin were measured in fasting sample s. RESULTS Hepatic suppression of glucose production during the clamp was significantly lower after HF ( 59.4 ± 11.0 % ) than HG ( 70.3 ± 10.5 % , P < 0.05 ) , whereas fasting glucose , insulin , and C-peptide did not differ between the interventions . Compared with HG , LDL cholesterol and total cholesterol were significantly higher after MF , HF , and HS , and free fatty acids were significantly increased after MF , but not after the two other interventions ( P < 0.05 ) . Subjects ’ energy intake during the interventions did not differ significantly from baseline intake . CONCLUSIONS This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose Overconsumption of fructose , particularly in the form of soft drinks , is increasingly recognized as a public health concern . The acute cardiovascular responses to ingesting fructose have not , however , been well-studied in humans . In this r and omized crossover study , we compared cardiovascular autonomic regulation after ingesting water and drinks containing either glucose or fructose in 15 healthy volunteers ( aged 21 - 33 yr ) . The total volume of each drink was 500 ml , and the sugar content 60 g. For 30 min before and 2 h after each drink , we recorded beat-to-beat heart rate , arterial blood pressure , and cardiac output . Energy expenditure was determined on a minute-by-minute basis . Ingesting the fructose drink significantly increased blood pressure , heart rate , and cardiac output but not total peripheral resistance . Glucose ingestion result ed in a significantly greater increase in cardiac output than fructose but no change in blood pressure and a concomitant decrease in total peripheral resistance . Ingesting glucose and fructose , but not water , significantly increased blood pressure variability and decreased cardiovagal baroreflex sensitivity . Energy expenditure increased by a similar amount after glucose and fructose ingestion , but fructose elicited a significantly greater increase in respiratory quotient . These results show that ingestion of glucose and fructose drinks is characterized by specific hemodynamic responses . In particular , fructose ingestion elicits an increase in blood pressure that is probably mediated by an increase in cardiac output without compensatory peripheral vasodilatation Using a crossover design , eight healthy volunteers r and omly received physiologic amounts ( ⅓ of each subject 's total carbohydrate intake ) of either fructose or sucrose as the primary source of simple sugar , incorporated into isocaloric diets comprised of typical American foods . After 7 and 14 days of consuming either of the two sugars , no change occurred in fasting glucose or insulin levels . In addition , total triglyceride , totalcholesterol , low-density-lipoprotein ( LDL ) cholesterol , and high-density-lipoprotein ( HDL ) cholesterol concentrations were unaltered . Since our study used conventional foods in normal eating patterns rather than contrived formulas or excessive amounts of simple sugar , our data indicate that there is no difference between sucrose or fructose on various lipid components or glucose and fasting insulin levels in the “ real world ” innormal subjects Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue . The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup ( HFCS ) . Methods This was a r and omized , prospect i ve , double blind trial , with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet .  The average caloric deficit achieved on the hypocaloric diets was 309 kcal . Results Reductions were observed in all measures of adiposity including body mass , BMI , % body fat , waist circumference and fat mass for all four hypocaloric groups , as well as reductions in the exercise only group for body mass , BMI and waist circumference . Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States Using a within-subject design , we gave subjects three different 520 - 530 kcal preloads in the form of puddings in a r and omized fashion at weekly intervals . The puddings contained either 50 g of fructose or glucose as the sole carbohydrate source in a protein and fat mixture , or 50 g fructose plus 15 g of starch .  Food intake was assessed 2.25 h after the preload was completed . Blood was drawn throughout and assayed for concentrations of glucose and insulin . When the preload contained fructose alone as the sole source of carbohydrate , subjects ate significantly fewer calories and less fat than when the preload contained glucose alone . When starch was added to the fructose preload , there was no significant reduction in calorie and fat intake . Effects on food intake paralleled the rise in plasma insulin levels produced by the different preloads . Implication s for use of fructose as an adjunct to weight control efforts are discussed The purpose of this study was to compare the physiological , sensory , and exercise performance responses to ingestion of 6 % glucose , 6 % fructose , and 6 % sucrose solutions during cycling exercise . Twelve subjects completed three sessions consisting of 115 min of intermittent cycle ergometer exercise at 65 - 80 % of VO2max followed by a timed performance bout requiring the completion of 600 pedal revolutions . During each of five 4-min rest periods , subjects consumed 3 ml.kg LBM-1 of one of the beverages . Beverages were presented in counterbalanced , double-blind fashion . Heart rate , VO2 , plasma urate , plasma lactate , respiratory exchange ratio , and carbohydrate combustion rates changed similarly among beverage treatment . However , fructose was associated with lower plasma glucose and serum insulin , a larger loss of plasma volume , greater gastrointestinal distress and relative perceived exertion ratings , and higher plasma or serum concentrations of free fatty acids , fructose , and cortisol values than sucrose or glucose ( P less than 0.05 ) . Compared to sucrose and glucose , fructose feeding also result ed in lower lactate and HR values during the performance bout ( P less than 0.05 ) . Mean + /- SE cycling performance times were faster with sucrose and glucose than with fructose : 419.4 + /- 21.0 s , 423.9 + /- 21.2 s , and 488.3 + /- 21.1 s , respectively ( P less than 0.05 ) . Relative to 6 % solutions of sucrose and glucose , ingestion of a 6 % fructose beverage is associated with gastrointestinal distress , compromised physiological response , and reduced exercise capacity OBJECTIVE To investigate prospect ively whether intake of total or type of sugar is associated with the risk of developing type 2 diabetes . The contribution of sugar intake to the pathogenesis of type 2 diabetes has not been settled in the context of primary prevention because of limited prospect i ve data . RESEARCH DESIGN AND METHODS The Women 's Health Study is a r and omized controlled trial of aspirin and vitamin E in the prevention of cardiovascular disease and cancer . A vali date d semiquantitative food frequency question naire was completed by 39,345 women aged 45 years and older . The main outcome was the incidence of type 2 diabetes . The predictor was sugar intake , including sucrose , glucose , fructose , and lactose . Using Cox proportional hazard models , multivariate RRs of type 2 diabetes for increasing quintiles of sugar intake compared with the lowest quintile were estimated . RESULTS Compared with the lowest quintile of sugar intake , the RRs and 95 % CIs for the highest quintiles were 0.84 ( 0.67 - 1.04 ) for sucrose , 0.96 ( 0.78 - 1.19 ) for fructose , 1.04 ( 0.85 - 1.28 ) for glucose , and 0.99 ( 0.80 - 1.22 ) for lactose , after adjustment for known risk factors for type 2 diabetes . Similar findings of no association were obtained in subgroup analyses stratified by BMI . CONCLUSIONS Intake of sugars does not appear to play a deleterious role in primary prevention of type 2 diabetes . These prospect i ve data support the recent American Diabetes Association 's guideline that a moderate amount of sugar can be incorporated in a healthy diet
The highest level of evidence from systematic review s and meta-analyses of controlled trials has not shown that fructose-containing sugars behave any differently from other forms of digestible carbohydrates .
Fructose-containing sugars can only lead to weight gain and other unintended harms on cardiometabolic risk factors insofar as the excess calories they provide .
Prospect i ve cohort studies , which provide the strongest observational evidence , have shown an association between fructose-containing sugars and cardiometabolic risk including weight gain , cardiovascular disease outcomes and diabetes only when restricted to sugar-sweetened beverages and not for sugars from other sources .
In fact , sugar-sweetened beverages are a marker of an unhealthy lifestyle and their drinkers consume more calories , exercise less , smoke more and have a poor dietary pattern .
Fructose-containing sugars are a focus of attention as a public health target for their putative role in obesity and cardiometabolic disease including diabetes .
The fructose moiety is singled out to be the primary driver for the harms of sugars due to its unique endocrine signal and pathophysiological role .
However , this is only supported by ecological studies , animal models of overfeeding and select human intervention studies with supraphysiological doses or lack of control for energy .