title: Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men 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 Sweetened Beverage Consumption, Incident Coronary Heart Disease, and Biomarkers of Risk in Men Differences in dietary-induced thermogenesis with various carbohydrates in normal and overweight men. Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women. Mechanisms for the acute effect of fructose on postprandial lipemia. Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. Predictors of weight gain in a Mediterranean cohort: the Seguimiento Universidad de Navarra Study 1. Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans. Reduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trial. Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Changes in water and beverage intake and long-term weight changes: results from three prospective cohort studies Short- and long-term eating habit modification predicts weight change in overweight, postmenopausal women: results from the WOMAN study. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women Carbohydrate-induced thermogenesis in liver cirrhosis: glucose vs. fructose. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients Increased postprandial glycaemia, insulinemia, and lipidemia after 10 weeks’ sucrose-rich diet compared to an artificially sweetened diet: a randomised controlled trial Effect of Eucaloric High- and Low-Sucrose Diets With Identical Macronutrient Profile on Insulin Resistance and Vascular Risk Effects of a short-term overfeeding with fructose or glucose in healthy young males. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study Acute effects of fructose and glucose ingestion with and without caffeine in young and old humans. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Carbohydrate-induced thermogenesis in obese women. Effect of insulin and catecholamines Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Fructose-rich beverages and risk of gout in women.
abstract: BACKGROUND It has been extensively shown , mainly in US population s , that sugar-sweetened beverages ( SSBs ) are associated with increased risk of type 2 diabetes ( T2D ) , but less is known about the effects of artificially sweetened beverages ( ASBs ) . OBJECTIVE We evaluated the association between self-reported SSB , ASB , and 100 % fruit juice consumption and T2D risk over 14 y of follow-up in the French prospect i ve Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospect i ve Investigation into Cancer and Nutrition cohort . DESIGN A total of 66,118 women were followed from 1993 , and 1369 incident cases of T2D were diagnosed during the follow-up . Cox regression models were used to estimate HRs and 95 % CIs for T2D risk . RESULTS The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs , respectively . Compared with nonconsumers , women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs ( 95 % CIs ) of 1.34 ( 1.05 , 1.71 ) and 2.21 ( 1.56 , 3.14 ) for women who consumed > 359 and > 603 mL/wk of SSBs and ASBs , respectively . Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage ( P = 0.0088 and P < 0.0001 , respectively ) . In sensitivity analyses , associations were partly mediated by BMI , although there was still a strong significant independent effect . No association was observed for 100 % fruit juice consumption . CONCLUSIONS Both SSB consumption and ASB consumption were associated with increased T2D risk . We can not rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes , and r and omized trials are required to prove a causal link between ASB consumption and T2D BACKGROUND & AIMS Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease . We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol ( TAG ) concentration and other liver parameters . DESIGN In a double-blind study , we r and omly assigned 32 healthy but central ly overweight men to groups that received either a high-fructose or high-glucose diet ( 25 % energy ) . These diets were provided during an initial isocaloric period of 2 weeks , followed by a 6-week washout period , and then again during a hypercaloric 2-week period . The primary outcome measure was hepatic level of TAG , with additional assessment s of TAG levels in serum and soleus muscle , hepatic levels of adenosine triphosphate , and systemic and hepatic insulin resistance . RESULTS During the isocaloric period of the study , both groups had stable body weights and concentrations of TAG in liver , serum , and soleus muscle . The high-fructose diet produced an increase of 22 ± 52 μmol/L in the serum level of uric acid , whereas the high-glucose diet led to a reduction of 23 ± 25 μmol/L ( P < .01 ) . The high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance , whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 ( P = .03 ) . During the hypercaloric period , participants in the high-fructose and high-glucose groups had similar increases in weight ( 1.0 ± 1.4 vs 0.6 ± 1.0 kg ; P = .29 ) and absolute concentration of TAG in liver ( 1.70 % ± 2.6 % vs 2.05 % ± 2.9 % ; P = .73 ) and serum ( 0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L ; P = .91 ) , and similar results in biochemical assays of liver function . Body weight changes were associated with changes in liver biochemistry and concentration of TAGs . CONCLUSIONS In the isocaloric period , overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes . However , in the hypercaloric period , both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups . This indicates an energy-mediated , rather than a specific macronutrient-mediated , effect . Clinical trials.gov no : NCT01050140 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 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 Background — Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus .  Few studies have tested for a relationship with coronary heart disease ( CHD ) or intermediate biomarkers . The role of artificially sweetened beverages is also unclear . Methods and Results — We performed an analysis of the Health Professionals Follow-Up Study , a prospect i ve cohort study including 42 883 men . Associations of cumulatively averaged sugar-sweetened ( eg , sodas ) and artificially sweetened ( eg , diet sodas ) beverage intake with incident fatal and nonfatal CHD ( myocardial infa rct ion ) were examined with proportional hazard models . There were 3683 CHD cases over 22 years of follow-up . Participants in the top quartile of sugar-sweetened beverage intake had a 20 % higher relative risk of CHD than those in the bottom quartile ( relative risk=1.20 ; 95 % confidence interval , 1.09–1.33 ; P for trend < 0.01 ) after adjustment for age , smoking , physical activity , alcohol , multivitamins , family history , diet quality , energy intake , body mass index , pre-enrollment weight change , and dieting . Artificially sweetened beverage consumption was not significantly associated with CHD ( multivariate relative risk=1.02 ; 95 % confidence interval , 0.93–1.12 ; P for trend=0.28 ) . Adjustment for self-reported high cholesterol , high triglycerides , high blood pressure , and diagnosed type 2 diabetes mellitus slightly attenuated these associations . Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides , C-reactive protein , interleukin-6 , and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein , lipoprotein(a ) , and leptin ( P<0.02 ) . Conclusions — Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids , inflammatory factors , and leptin . Artificially sweetened beverage intake was not associated with CHD risk or biomarkers The purpose of this investigation was to learn whether the thermogenic effect in man of sucrose and glucose was similar and whether normal weight and overweight subjects responded in a similar manner . Dietary-induced thermogenesis was calculated for the period 15 to 180 min after ingestion of sucrose or glucose in six normal weight and five obese subjects . The metabolic rate was calculated from the oxygen consumption and carbon dioxide output utilizing the ventilated hood technique . In normal weight subjects , the total dietary-induced thermogenesis was significantly greater after sucrose than after glucose ( p less than 0.005 ) but the difference was much less marked in the obese subjects BACKGROUND Previous short-term studies ( < or = 6 h ) showed differences in energy expenditure ( EE ) and macronutrient oxidation in response to overfeeding with different types of dietary carbohydrate . This finding could have implication s for obesity . OBJECTIVE We used 96-h continuous whole-body calorimetry in 8 lean and 5 obese women to assess metabolic disposal ( energy dissipation and glycogen or fat storage ) of a controlled excess of dietary energy supplied as different carbohydrate sources or as fat . DESIGN Five dietary treatments were applied in r and om order : energy balance ( control ) and overfeeding by 50 % of energy requirements with fat ( O(fat ) ) or predominantly with glucose , fructose , or sucrose ( O(cho ) ) .  Macronutrient oxidation rates were assessed from nonprotein gaseous exchanges . Net macronutrient balances were calculated as cumulative differences between intake and oxidation . RESULTS Increased EE in response to overfeeding dissipated 7.9 % of the energy excess with a variation in EE of < 1.7 % across overfeeding treatments ( NS ) . EE during the O(fat ) treatment significantly exceeded that during the control treatment in the lean but not in the obese women . There were no significant differences between lean and obese women in macronutrient oxidation or balances , so data were pooled . O(cho ) induced glycogen storage on day 1 ( approximately 100 g ) but thereafter progressively stimulated carbohydrate oxidation so that balance was reached on days 3 and 4 . Fat oxidation was proportionately suppressed . Of the excess carbohydrate , 74 % was oxidized ; there were no significant differences between the various O(cho ) treatments . O(fat ) stimulated fat oxidation by 18 % and suppressed carbohydrate oxidation . On average , 12 % of the excess energy was stored as glycogen and 88 % as fat ; there was no significant difference between overfeeding treatments . CONCLUSION There was no significant difference in fat balance during controlled overfeeding with fat , fructose , glucose , or sucrose BACKGROUND A high fructose intake can lead to postpr and ial hypertriacylglycerolemia . The underlying mechanism is unclear . OBJECTIVE The objective of the study was to investigate the mechanisms involved in fructose-induced hypertriacylglycerolemia and the contribution of de novo lipogenesis in an acute setting . DESIGN In a r and omized , crossover study , 14 subjects were given a fructose or glucose test meal after an overnight fast . [(2)H2]Palmitate and [U(13)C]d-fructose or [U(13)C]d-glucose were added to trace the h and ling of dietary fats and the fate of dietary sugars in the body . Blood sample s were taken before and after the meal . Respiratory exchange ratio was measured by using indirect calorimetry , and breath sample s were collected . RESULTS Plasma triacylglycerol and VLDL-triacylglycerol concentrations were significantly higher ( P = 0.001 for both ) , whereas the concentrations of insulin and [(2)H2]palmitate in nonesterified fatty acids were significantly lower after fructose than after glucose ( P = 0.002 and 0.03 , respectively ) . The respiratory exchange ratio was higher after fructose ( P = 0.04 ) ; significantly ( P = 0.003 ) more carbon from sugars was recovered in breath carbon dioxide over 6 h after fructose ( 30.5 % ) than after glucose ( 24.5 % ) . At 240 min , newly synthesized fatty acids from fructose made up approximately 0.4 % of circulating VLDL-triacylglycerol , whereas newly synthesized triacylglycerol-glycerol made up 38 % . Newly synthesized fatty acids and triacylglycerol-glycerol from glucose contributed almost none of VLDL-triacylglycerol ( P = 0.002 and 0.007 for glucose and fructose , respectively ) . CONCLUSIONS The lower insulin excursion after fructose may result in less activation of adipose tissue lipoprotein lipase , which led to impaired triacylglycerol clearance . The contribution of de novo lipogenesis to fructose-induced hypertriacylglycerolemia is small , but its effect on altering the partitioning of fatty acids toward esterification may be considerable Using a within-subjects design , we gave over-weight and normal-weight subjects a 500-mL drink of fructose , glucose , or aspartame diluted in lemon-flavored water or plain water in a r and omized fashion at about weekly intervals . Food intake was assessed at a buffet lunch that began 38 min after the preload was completed . Blood was drawn throughout and assayed for concentrations of glucose , insulin , glucagon , and free fatty acid . When subjects drank the fructose preload , they subsequently ate fewer overall calories and fewer grams of fat than when they drank any of the other preloads . The aspartame load did not stimulate intake beyond the plain-water control . The effects of the oxidation of fructose as a possible mechanism for the reduction in food intake is discussed . The effects of insulin in stimulating intake are also discussed BACKGROUND High consumption of sugar-sweetened drinks has been associated with  weight gain and obesity in the United States . This trend may also be affecting population s with different eating patterns who increasingly are adopting typical US dietary patterns . OBJECTIVE We assessed whether the consumption of sweetened drinks and other food items increased the likelihood of weight gain in a Mediterranean population . DESIGN This was a prospect i ve cohort analysis of 7194 men and women with a mean age of 41 y who were followed-up for a median of 28.5 mo with mailed question naires . Dietary exposure was assessed with a previously vali date d semiquantitative food-frequency question naire . RESULTS During follow-up , we observed that 49.5 % of the participants increased their weight ( x weight gain : 0.64 kg ; 95 % CI : 0.55 , 0.73 kg ) . In the participants who had gained > or =3 kg in the 5 y before baseline , the adjusted odds ratio of subsequent weight gain for the fifth quintile compared with the first quintile of sugar-sweetened soft drink consumption was 1.6 ( 95 % CI : 1.2 , 2.1 ; P for trend = 0.02 ) . This association was absent in the participants who had not gained weight in the 5-y period before baseline . The consumption of hamburgers , pizza , and sausages ( as a proxy for fast-food consumption ) was also independently associated with weight gain ( adjusted odds ratio for the fifth compared with the first quintile = 1.2 ; 95 % CI : 1.0 , 1.4 ; P for trend = 0.05 ) . We also found a significant , but weaker , association between weight gain and both red meat and sweetened fruit juice consumption . CONCLUSION In a Mediterranean cohort , particularly in the participants who had already gained weight , an increased consumption of sugar-sweetened soft drinks and of hamburgers , pizza , and sausages was associated with a higher risk of additional subsequent weight gain BACKGROUND A high dietary protein intake has been shown to blunt the deposition of intrahepatic lipids in high-fat- and high-carbohydrate-fed rodents and humans . OBJECTIVE The aim of this study was to evaluate the effect of essential amino acid supplementation on the increase in hepatic fat content induced by a high-fructose diet in healthy subjects . DESIGN Nine healthy male volunteers were studied on 3 occasions in a r and omized , crossover design after 6 d of dietary intervention . Dietary conditions consisted of a weight-maintenance balanced diet ( control ) or the same balanced diet supplemented with 3 g fructose · kg(-1 ) · d(-1 ) and 6.77 g of a mixture of 5 essential amino acids 3 times/d ( leucine , isoleucine , valine , lysine , and threonine ) ( HFrAA ) or with 3 g fructose · kg(-1 ) · d(-1 ) and a maltodextrin placebo 3 times/d ( HFr ) ; there was a washout period of 4 to 10 wk between each condition . For each condition , the intrahepatocellular lipid ( IHCL ) concentration , VLDL-triglyceride concentration , and VLDL-[(13)C]palmitate production were measured after oral loading with [(13)C]fructose . RESULTS HFr increased the IHCL content ( 1.27 ± 0.31 compared with 2.74 ± 0.55 vol % ; P < 0.05 ) and VLDL-triglyceride ( 0.55 ± 0.06 compared with 1.40 ± 0.15 mmol/L ; P < 0.05 ) . HFr also enhanced VLDL-[(13)C]palmitate production . HFrAA significantly decreased IHCL compared with HFr ( to 2.30 ± 0.43 vol% ; P < 0.05 ) but did not change VLDL-triglyceride concentrations or VLDL-[(13)C]palmitate production . CONCLUSIONS Supplementation with essential amino acids blunts the fructose-induced increase in IHCL but not hypertriglyceridemia . This is not because of inhibition of VLDL-[(13)C]palmitate production . This trial was registered at www . clinical trials.gov as NCT01119989 BACKGROUND Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population , but their causal relation remains unclear . OBJECTIVE The objective of this study was to examine how changes in beverage consumption affect  weight change among adults . DESIGN This was a prospect i ve study of 810 adults participating in the PREMIER trial , an 18-mo r and omized , controlled , behavioral intervention trial .  Measurements ( weight , height , and 24-h dietary recall ) were made at baseline , 6 mo , and 18 mo . RESULTS Baseline mean intake of liquid calories was 356 kcal/d ( 19 % of total energy intake ) . After potential confounders and intervention assignment were controlled for , a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg ( 95 % CI : 0.11 , 0.39 ; P < 0.001 ) at 6 mo and of 0.24 kg ( 95 % CI : 0.06 , 0.41 ; P = 0.008 ) at 18 mo . A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss . Of the individual beverages , only intake of sugar-sweetened beverages ( SSBs ) was significantly associated with weight change . A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg ( 95 % CI : 0.11 , 0.82 ; P = 0.006 ) at 6 mo and of 0.65 kg ( 95 % CI : 0.22 , 1.09 ; P = 0.003 ) at 18 mo . CONCLUSIONS These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain . This trial was registered at clinical trials.gov as NCT00000616 BACKGROUND Type 2 diabetes mellitus is an increasingly serious health problem among African American women . Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third ; however , to our knowledge , no data are available on African Americans regarding this issue . Our objective was to examine the association between consumption of sugar-sweetened beverages , weight gain , and incidence of type 2 diabetes mellitus in African American women . METHODS A prospect i ve follow-up study of 59,000 African American women has been in progress since 1995 . Participants reported on food and beverage consumption in 1995 and 2001 . Biennial follow-up question naires ascertained new diagnoses of type 2 diabetes . The present analyses included 43,960 women who gave complete dietary and weight information and were free from diabetes at baseline . We identified 2713 incident cases of type 2 diabetes mellitus during 338,884 person-years of follow-up . The main outcome measure was the incidence of type 2 diabetes mellitus . RESULTS The incidence of type 2 diabetes mellitus was higher with higher intake of both sugar-sweetened soft drinks and fruit drinks . After adjustment for confounding variables including other dietary factors , the incidence rate ratio for 2 or more soft drinks per day was 1.24 ( 95 % confidence interval , 1.06 - 1.45 ) . For fruit drinks , the comparable incidence rate ratio was 1.31 ( 95 % confidence interval , 1.13 - 1.52 ) . The association of diabetes with soft drink consumption was almost entirely mediated by body mass index , whereas the association with fruit drink consumption was independent of body mass index . CONCLUSIONS Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women . While there has been increasing public awareness of the adverse health effects of soft drinks , little attention has been given to fruit drinks , which are often marketed as a healthier alternative to soft drinks OBJECTIVE : To examine the long-term relationship between changes in water and beverage intake and weight change . SUBJECTS : Prospect i ve cohort studies of 50 013 women aged 40–64 years in the Nurses ’ Health Study ( NHS , 1986–2006 ) , 52 987 women aged 27–44 years in the NHS II ( 1991–2007 ) and 21 988 men aged 40–64 years in the Health Professionals Follow-up Study ( 1986–2006 ) without obesity and chronic diseases at baseline . MEASURES : We assessed the association of weight change within each 4-year interval , with changes in  beverage intakes and other  lifestyle behaviors  during the same period . Multivariate linear regression with robust variance and accounting for within-person repeated measures were used to evaluate the association . Results across the three cohorts were pooled by an inverse-variance-weighted meta- analysis . RESULTS : Participants gained an average of 1.45 kg ( 5th to 95th percentile : −1.87 to 5.46 ) within each 4-year period . After controlling for age , baseline body mass index and changes in other lifestyle behaviors ( diet , smoking habits , exercise , alcohol , sleep duration , TV watching ) , each 1 cup per day increment of water intake was inversely associated with weight gain within each 4-year period ( −0.13 kg ; 95 % confidence interval ( CI ) : −0.17 to −0.08 ) . The associations for other beverages were : sugar-sweetened beverages ( SSBs ) ( 0.36 kg ; 95 % CI : 0.24–0.48 ) , fruit juice ( 0.22 kg ; 95 % CI : 0.15–0.28 ) , coffee ( −0.14 kg ; 95 % CI : −0.19 to −0.09 ) , tea ( −0.03 kg ; 95 % CI : −0.05 to −0.01 ) , diet beverages ( −0.10 kg ; 95 % CI : −0.14 to −0.06 ) , low-fat milk ( 0.02 kg ; 95 % CI : −0.04 to 0.09 ) and whole milk ( 0.02 kg ; 95 % CI : −0.06 to 0.10 ) . We estimated that replacement of 1 serving per day of SSBs by 1 cup per day of water was associated with 0.49 kg ( 95 % CI : 0.32–0.65 ) less weight gain over each 4-year period , and the replacement estimate of fruit juices by water was 0.35 kg ( 95 % CI : 0.23–0.46 ) . Substitution of SSBs or fruit juices by other beverages ( coffee , tea , diet beverages , low-fat and whole milk ) were all significantly and inversely associated with weight gain . CONCLUSION : Our results suggest that increasing water intake in place of SSBs or fruit juices is associated with lower long-term weight gain BACKGROUND St and ard behavioral obesity treatment produces poor long-term results . Focusing on healthy eating behaviors rather than energy intake may be an alternative strategy . In addition , important behaviors might differ for short- vs long-term weight control . OBJECTIVE Our aim was to describe and compare associations between changes in eating behaviors and weight after 6 and 48 months . DESIGN We performed secondary analysis of data collected during a r and omized weight-loss intervention trial with 48-month follow-up . PARTICIPANTS We studied 481 overweight and obese postmenopausal women enrolled in the Women on the Move through Activity and Nutrition ( WOMAN ) Study . MAIN OUTCOME MEASURES We measured changes in weight from baseline to 6 and 48 months . STATISTICAL ANALYSES PERFORMED Linear regression models were used to examine the associations between 6- and 48-month changes in eating habits assessed by the Conner Diet Habit Survey and changes in weight . Analyses were conducted in the combined study population and stratified by r and omization group . RESULTS At 6 months in the combined population , weight loss was independently associated with decreased desserts ( P<0.001 ) , restaurant eating ( P=0.042 ) , sugar-sweetened beverages ( P=0.009 ) , and fried foods ( P<0.001 ) , and increased fish consumption ( P=0.003 ) . Results were similar in intervention participants ; only reduced desserts and fried foods associated with weight loss in controls . At 48 months in the combined population , weight loss was again associated with decreased desserts ( P=0.003 ) and sugar-sweetened beverages ( P=0.011 ) , but also decreased meats/cheeses ( P=0.024 ) and increased fruits/vegetables ( P<0.001 ) . Decreased meats/cheeses predicted weight loss in intervention participants ; desserts , sugar-sweetened beverages , and fruits/vegetables were independently associated in controls . CONCLUSIONS Changes in eating behaviors were associated with weight change , although important behaviors differed for short- and long-term weight change and by r and omization group . Future studies should determine whether interventions targeting these behaviors could improve long-term obesity treatment outcomes BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P < 0.01 ) , skeletal muscle fat ( 117 - 221 % ; P < 0.05 ) , visceral fat ( 24 - 31 % ; P < 0.05 ) , blood triglycerides ( 32 % ; P < 0.01 ) , and total cholesterol ( 11 % ; P < 0.01 ) . Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P < 0.05 ) . Otherwise , diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647 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 Background / Objectives : The results of short-term studies in humans suggest that , compared with glucose , acute consumption of fructose leads to increased postpr and ial energy expenditure and carbohydrate oxidation and decreased postpr and ial fat oxidation . The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions . Subjects/ Methods : As part of a parallel arm study , overweight/obese male and female subjects , 40–72 years , consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 weeks . Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention . Results : Consumption of fructose , but not glucose , led to significant decreases of net postpr and ial fat oxidation and significant increases of net postpr and ial carbohydrate oxidation ( P<0.0001 for both ) . Resting energy expenditure ( REE ) decreased significantly from baseline values in subjects consuming fructose ( P=0.031 ) but not in those consuming glucose . Conclusions : Increased consumption of fructose for 10 weeks leads to marked changes of postpr and ial substrate utilization including a significant reduction of net fat oxidation . In addition , we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks Reduced thermic response after a glucose load has been reported in liver cirrhosis . To determine the mechanism and the site of this phenomenon , the effects of glucose and fructose on energy expenditure ( EE ) were measured in seven well-nourished cirrhotic patients and in six healthy control subjects .  EE and fuel utilization were measured via indirect calorimetry for 3 h after oral glucose or fructose administration ( 1 g/kg body wt ) . After a glucose load , plasma glucose and insulin concentrations were higher in cirrhotic patients than in control subjects ( p < 0.05 ) . During the glucose trial , the cumulative incremental changes in EE over the 3-h measurement period were lower ( p < 0.01 ) in patients than in the control subjects ( 0.98 + /- 0.13 vs. 1.70 + /- 0.23 kJ.kg-1.3 h-1 ) . After fructose ingestion , the cumulative changes in the EE of control subjects ( 1.76 + /- 0.24 kJ.kg-1.3 h-1 ) and cirrhotic patients ( 1.59 + /- 0.15 kJ.kg-1.3 h-1 ) were similar . In cirrhotic patients , the EE increase after fructose was higher than after glucose ( p < 0.05 ) . After glucose and fructose ingestion , no difference was observed between the carbohydrate oxidation in cirrhotic patients and that in control subjects , and lipid oxidation was suppressed to the same extent in both groups . We conclude that glucose-induced thermogenesis is impaired in liver cirrhosis , whereas fructose can normalize the thermic response . Because fructose is chiefly metabolized in the liver , these findings suggest that extrahepatic tissues are the site of defective thermogenesis in liver cirrhosis Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism . Because fructose , unlike glucose , does not stimulate insulin secretion , we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose . Blood sample s were collected every 30 - 60 min for 24 h from 12 normal-weight women on 2 r and omized days during which the subjects consumed three meals containing 55 , 30 , and 15 % of total kilocalories as carbohydrate , fat , and protein , respectively , with 30 % of kilocalories as either a fructose-sweetened [ high fructose ( HFr ) ] or glucose-sweetened [ high glucose ( HGl ) ] beverage . Meals were isocaloric in the two treatments . Postpr and ial glycemic excursions were reduced by 66 + /- 12 % , and insulin responses were 65 + /- 5 % lower ( both P < 0.001 ) during HFr consumption . The area under the curve for leptin during the first 12 h ( -33 + /- 7 % ; P < 0.005 ) , the entire 24 h ( -21 + /- 8 % ; P < 0.02 ) , and the diurnal amplitude ( peak - nadir ) ( 24 + /- 6 % ; P < 0.0025 ) were reduced on the HFr day compared with the HGl day . In addition , circulating levels of the orexigenic gastroenteric hormone , ghrelin , were suppressed by approximately 30 % 1 - 2 h after ingestion of each HGl meal ( P < 0.01 ) , but postpr and ial suppression of ghrelin was significantly less pronounced after HFr meals ( P < 0.05 vs. HGl ) . Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day ( P < 0.005 ) . Because insulin and leptin , and possibly ghrelin , function as key signals to the central nervous system in the long-term regulation of energy balance , decreases of circulating insulin and leptin and increased ghrelin concentrations , as demonstrated in this study , could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols ( PPs ) in counteracting the metabolic alterations of high-fructose diet , including oxidative stress and insulin resistance ( IR ) , in healthy volunteers with high metabolic risk . RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients ( 18 men and 20 women ) were r and omized in a double-blind controlled trial between a grape PP ( 2 g/day ) and a placebo ( PCB ) group . Subjects were investigated at baseline and after 8 and 9 weeks of supplementation , the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose . The primary end point was the protective effect of  grape PPs  on fructose-induced IR . RESULTS In the PCB group , fructose induced 1 ) a 20 % decrease in hepatic insulin sensitivity index ( P < 0.05 ) and an 11 % decrease in glucose infusion rate ( P < 0.05 ) as evaluated during a two-step hyperinsulinemic-euglycemic clamp , 2 ) an increase in systemic ( urinary F2-isoprostanes ) and muscle ( thiobarbituric acid – reactive substances and protein carbonylation ) oxidative stress ( P < 0.05 ) , and 3 ) a downregulation of mitochondrial genes and decreased mitochondrial respiration ( P < 0.05 ) . All the deleterious effects of fructose were fully blunted by grape PP supplementation . Antioxidative defenses , inflammatory markers , and main adipokines were affected neither by fructose nor by grape PPs . CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR . The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition Background The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear . Objective To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postpr and ial metabolic profiles after 10 weeks . Design Healthy overweight subjects were r and omised to consume drinks and foods sweetened with either sucrose ( ∼2 g/kg body weight ) ( n = 12 ) or artificial sweeteners ( n = 11 ) as supplements to their usual diet . Supplements were similar on the two diets and consisted of beverages ( ∼80 weight% ) and solid foods ( yoghurts , marmalade , ice cream , stewed fruits ) . The rest of the diet was free of choice and ad libitum . Before ( week 0 ) and after the intervention ( week 10 ) fasting blood sample s were drawn and in week 10 , postpr and ial blood was sample d during an 8-hour meal test ( breakfast and lunch ) . Results After 10 weeks postpr and ial glucose , insulin , lactate , triglyceride , leptin , glucagon , and GLP-1 were all significantly higher in the sucrose compared with the sweetener group . After adjusting for differences in body weight changes and fasting values ( week 10 ) , postpr and ial glucose , lactate , insulin , GIP , and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake , postpr and ial lactate , insulin , GIP , and GLP-1 levels were still significantly higher on the sucrose-rich diet . Conclusion A sucrose-rich diet consumed for 10 weeks result ed in significant elevations of postpr and ial glycaemia , insulinemia , and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects The long-term impact of dietary carbohydrate type , in particular sucrose , on insulin resistance and the development of diabetes and atherosclerosis is not established . Current guidelines for the healthy population advise restriction of sucrose intake . We investigated the effect of high- versus low-sucrose diet ( 25 vs. 10 % , respectively , of total energy intake ) in 13 healthy subjects aged 33 ± 3 years ( mean ± SE ) , BMI 26.6 ± 0.9 kg/m2 , in a r and omized crossover design with sequential 6-week dietary interventions separated by a 4-week washout . Weight maintenance , eucaloric diets with identical macronutrient profiles and fiber content were design ed . All food was weighed and distributed . Insulin action was assessed using a two-step euglycemic clamp ;  glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis . There was no change in weight across the study . Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet . Glycemic profiles and measures of vascular compliance did not change . A rise in total and LDL cholesterol was observed . In this study , a high-sucrose intake as part of an eucaloric , weight-maintaining diet had no detrimental effect on insulin sensitivity , glycemic profiles , or measures of vascular compliance in healthy nondiabetic subjects 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 Objective To examine the relation between intake of sugar sweetened soft drinks and fructose and the  risk of incident gout in men . Design Prospect i ve cohort over 12 years . Setting Health professionals follow-up study . Participants 46 393 men with no history of gout at baseline who provided information on intake of soft drinks and fructose through vali date d food frequency question naires . Main outcome measure Incident cases of gout meeting the American College of Rheumatology survey criteria for gout . Results During the 12 years of follow-up 755 confirmed incident cases of gout were reported . Increasing intake of sugar sweetened soft drinks was associated with an increasing risk of gout . Compared with consumption of less than one serving of sugar sweetened soft drinks a month the multivariate relative risk of gout for 5 - 6 servings a week was 1.29 ( 95 % confidence interval 1.00 to 1.68 ) , for one serving a day was 1.45 ( 1.02 to 2.08 ) , and for two or more servings a day was 1.85 ( 1.08 to 3.16 ; P for trend=0.002 ) . Diet soft drinks were not associated with risk of gout ( P for trend=0.99 ) . The multivariate relative risk of gout according to increasing fifths of fructose intake were 1.00 , 1.29 , 1.41 , 1.84 , and 2.02 ( 1.49 to 2.75 ; P for trend < 0.001 ) . Other major contributors to fructose intake such as total fruit juice or fructose rich fruits ( apples and oranges ) were also associated with a higher risk of gout ( P values for trend < 0.05 ) . Conclusions Prospect i ve data suggest that consumption of sugar sweetened soft drinks and fructose is strongly associated with an increased  risk of gout in men . Furthermore , fructose rich fruits and fruit juices may also increase the risk .  Diet soft drinks were not associated with the risk of gout Aging is associated with a decline in energy expenditure ( EE ) , glucose intolerance , and a reduction in body nitrogen content . In addition , a reduction in the thermic response to glucose but not to fructose or protein has been reported in the elderly . The present study was conducted to further examine nutrient-induced thermogenesis and the effects of specific sugars on amino acid metabolism in relation to age . After 3 days on a weight-maintaining , 250-g carbohydrate diet , 16 healthy non-obese men and women in two age groups ( 18 to 29 and 66 to 80 years ) consumed on 4 different days 500 mL of either a 75-g fructose or 75-g glucose solution , with or without 300 mg caffeine or vitamin C as a placebo .  Blood substrate and hormone levels and EE , using indirect calorimetry , were measured at timed intervals for 3 hours after consumption of the drinks . There was no difference in the carbohydrate-induced increase in EE in either young or old even after adjustments for body weight and fat-free mass ( FFM ) . An approximately 20-fold increase in serum caffeine levels increased EE in both groups ( P < .003 ) , but had minimal effects on substrate and hormone responses . In contrast to glucose , fructose induced a marked elevation in plasma alanine from combined basal levels of 301 + /- 24 to approximately 500 + /- 18 mumol/L ( mean + /- SEM ) in both groups ( P < .001 ) . However , both fructose and glucose ingestion result ed in a similar decline in branched-chain and aromatic amino acids . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Results of studies on diet-induced thermogenesis in obese persons are contradictory . A number of factors have been postulated to mediate the obligatory and facultative component of thermogenesis . This study was design ed to investigate some further factors mediating the carbohydrate- induced thermogenesis in obese women . In 13 obese women , thermogenic responses to glucose and fructose were compared and related to subsequent hormonal changes . The thermogenic effect after fructose ingestion was significantly ( p<0.006 ) higher in comparison with glucose , despite lower values for both glucose and insulin concentrations . Carbohydrate oxidation was significantly higher after fructose ( 81±7 E% vs 62±10 E% p<0.01 ) while oxidation of fat was lower ( 10±9 E% vs 21±12 E% p<0.01 ) . These effects may partly be due to the de novo lipogenesis and /or to changes in cellular metabolism . No clear relationship could be found between thermogenesis and the activity of the sympathetic nervous system , as expressed by urinary catecholamine levels . These results indicate that not insulin but the cellular rate of carbohydrate metabolism is responsible for the thermogenic response to different carbo-nutrients BACKGROUND Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance . OBJECTIVE The aim was to assess the effects of fructose , a potent stimulator of hepatic de novo lipogenesis , on intrahepatocellular lipids ( IHCLs ) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders . DESIGN Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet ( 3.5 g x kg FFM(-1 ) x d(-1 ) , + 35 % energy intake ) . Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp ( 0.3 and 1.0 mU x kg(-1 ) x min(-1 ) ) , together with 6,6-[2H2]glucose . IHCLs and intramyocellular lipids ( IMCLs ) were measured by 1H-magnetic resonance spectroscopy . RESULTS The OffT2D group had significantly ( P < 0.05 ) higher IHCLs ( + 94 % ) , total triacylglycerols ( + 35 % ) , and lower whole-body insulin sensitivity ( -27 % ) than did the control group . The high-fructose diet significantly increased IHCLs ( control : + 76 % ; OffT2D : + 79 % ) , IMCLs ( control : + 47 % ; OffT2D : + 24 % ) , VLDL-triacylglycerols ( control : + 51 % ; OffT2D : + 110 % ) , and fasting hepatic glucose output ( control : + 4 % ; OffT2D : + 5 % ) . Furthermore , the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group ( group x diet interaction : P < 0.05 ) . CONCLUSIONS A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity . Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group , which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes . This trial was registered at clinical trials.gov as NCT00523562 CONTEXT Fructose-rich beverages such as sugar-sweetened soda and orange juice can increase serum uric acid levels and , thus , the risk of gout , but prospect i ve data on the relationship are limited . OBJECTIVE To examine the relationship between intake of fructose-rich beverages and fructose and the risk of incident gout among women . DESIGN , SETTING , AND PARTICIPANTS In the Nurses ' Health Study , a US prospect i ve cohort study spanning 22 years ( 1984 - 2006 ) , we analyzed data from 78,906 women with no history of gout at baseline who provided information on intake of beverages and fructose through vali date d food frequency question naires . MAIN OUTCOME MEASURE Incident cases that met the American College of Rheumatology survey criteria for gout . RESULTS During 22 years of follow-up , we documented 778 confirmed incident cases of gout . Increasing intake of sugar-sweetened soda was independently associated with increasing risk of gout . Compared with consumption of less than 1 serving per month of sugar-sweetened soda , the multivariate relative risk of gout for 1 serving per day was 1.74 ( 95 % confidence interval [ CI ] , 1.19 - 2.55 ) and for 2 or more servings per day was 2.39 ( 95 % CI , 1.34 - 4.26 ) ( P<.001 for trend ) . The corresponding relative risks for orange juice were 1.41 ( 95 % CI , 1.03 - 1.93 ) and 2.42 ( 95 % CI , 1.27 - 4.63 ) ( P = .02 for trend ) . The absolute risk differences corresponding to these relative risks were 36 and 68 cases per 100,000 person-years for sugar-sweetened soda and 14 and 47 cases per 100,000 person-years for orange juice , respectively . Diet soft drinks were not associated with the risk of gout ( P = .27 for trend ) . Compared with the lowest quintile of fructose intake , the multivariate relative risk of gout in the top quintile was 1.62 ( 95 % CI , 1.20 - 2.19 ; P = .004 for trend ) ( risk difference of 28 cases per 100,000 person-years ) . CONCLUSION Among this cohort of women , consumption of fructose-rich beverages is associated with an increased risk of incident gout , although the contribution of these beverages to the risk of gout in the population is likely modest given the low incidence rate among women
target: A literature analysis supported links between  sugar  intake and both total energy intake and body weight gain , and between sugar intake and blood triglycerides independently of total energy intake .
  The effects of sugar on blood triglycerides were shown to be mediated by the fructose component of sucrose and were observed with an intake of fructose > 50 g/day .
  In addition , prospect i ve cohort studies showed associations between sugar intake and the risk of diabetes/insulin resistance , cardiovascular diseases , NAFLD , and hyperuricemia .
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