Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Fructose prefeeding reduces the glycemic response to a high-glycemic index, starchy food in humans. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. The effectiveness of yoga to prevent diabetes mellitus type 2 Glycemic, hormone, and appetite responses to monosaccharide ingestion in patients with type 2 diabetes. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Dietary fiber and the glycemic index: a background paper for the Nordic Nutrition Recommendations 2012 Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Walking to Work Is an Independent Predictor of Incidence of Type 2 Diabetes in Japanese Men Fructose ingestion acutely elevates blood pressure in healthy young humans. Effects of grain, fructose, and histidine on ruminal pH and fermentation products during an induced subacute acidosis protocol. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients Consumption of a Diet Low in Advanced Glycation End Products for 4 Weeks Improves Insulin Sensitivity in Overweight Women Fructose and insulin sensitivity in patients with type 2 diabetes. Sweetener augmentation of serum triacylglycerol during a fat challenge test in humans.
OBJECTIVE In normal adults , a small ( catalytic ) dose of fructose administered with glucose decreases the glycemic response to a glucose load , especially in those with the poorest glucose tolerance . We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Five adults with type 2 diabetes underwent an oral glucose tolerance test ( OGTT ) on two separate occasions , at least 1 week apart . Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose ( OGTT + F or OGTT - F ) , in r and om order . Arterialized blood sample s were collected from a heated dorsal h and vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward . RESULTS The area under the curve ( AUC ) of the plasma glucose response was reduced by fructose administration in all subjects ; the mean AUC during the OGTT + F was 14 % less than that during the OGTT - F ( P < 0.05 ) . The insulin AUC was decreased 21 % with fructose administration ( P = 0.2 ) . Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50 % of that observed during the OGTT + F ( P < 0.05 ) . Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs . CONCLUSIONS Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes , and this effect is not a result of stimulation of insulin secretion The study objective was to determine whether a small dose of fructose administered before or simultaneously with a high glycemic index , starchy food decreases postpr and ial glycemic response .  Nondiabetic healthy adults ( n = 31 ; mean + /- SEM : age , 26 + /- 1 y ; weight , 66.1 + /- 2.6 kg ; body mass index , 23.3 + /- 0.6 kg/m(2 ) ) were studied in a r and omized crossover design . Treatments consisted of 50 g available carbohydrate from instant mashed potatoes fed alone ( control ) or with 10 g fructose fed 60 , 30 or 0 min before the potato meal . Capillary finger-stick blood sample s were analyzed for glucose concentration at -60 , -30 , 0 , 15 , 30 , 45 , 60 , 90 and 120 min relative to the ingestion of the potato meal . Compared with the control , the positive incremental area under the glucose curve was reduced 25 and 27 % ( P < 0.01 ) when fructose was fed either 60 or 30 min before the meal , respectively . In contrast to previous studies demonstrating that immediate administration of a small amount of fructose lowers the glycemic response to a glucose solution , we found that fructose must be consumed before a starchy food to reduce postpr and ial glycemia In animal models , a small ( catalytic ) dose of fructose administered with glucose decreases the glycemic response to the glucose load . Therefore , we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers ( 5 men and 6 women ) . Each subject underwent an oral glucose tolerance test ( OGTT ) on 2 separate occasions , at least 1 week apart . Each OGTT consisted of 75 g glucose with or without 7.5 g fructose ( OGTT+F or OGTT-F ) , in r and om order .  Arterialized blood sample s were obtained from a heated dorsal h and vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward . The area under the curve ( AUC ) of the change in plasma glucose was 19 % less in OGTT+F vs. OGTT-F ( P : < 0.05 ) . Glucose tolerance was improved by fructose in 9 subjects and worsened in 2 . All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F ( 31 + /- 5 % decrease ) . The insulin AUC did not differ between the 2 studies . Of the 9 subjects with improved glucose tolerance during the OGTT+F , 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50 % greater during the OGTT+F ( P : < 0.05 ) . Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT . In conclusion , low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response .  Fructose appears most effective in those normal individuals who have the poorest glucose tolerance Background Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome . Mechanisms by which dietary fructose mediates metabolic changes are poorly understood . This study compared the effects of fructose , glucose and sucrose consumption on post-postpr and ial lipemia and low grade inflammation measured as hs-CRP . Methods This was a r and omized , single blinded , cross-over trial involving healthy subjects ( n = 14 ) . After an overnight fast , participants were given one of 3 different isocaloric drinks , containing 50 g of either fructose or glucose or sucrose dissolved in water .  Blood sample s were collected at baseline , 30 , 60 and 120 minutes post intervention for the analysis of blood lipids , glucose , insulin and high sensitivity C-reactive protein ( hs-CRP ) . Results Glucose and sucrose supplementation initially result ed in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours . Change in plasma cholesterol , LDL and HDL-cholesterol ( measured as area under curve , AUC ) was significantly higher when participants consumed fructose compared with glucose or sucrose ( P < 0.05 ) . AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention . Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose ( P < 0.05 ) , but not sucrose ( P = 0.07 ) . Conclusion This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals . The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets . Registration number for clinical Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses .  Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with  colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated  colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer Background : Type 2 diabetes mellitus ( T2DM ) is becoming a leading problem worldwide . Emerging reports reveal alarming evidence of increasing prevalence of T2DM that has reached p and emic levels . Despite the significant incidence , there are limited reliable data re sources and comprehensive systematic review and meta- analysis on the effects of yoga on people who are a prediabetic or high risk for developing T2DM . Objective : The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the effects of yoga on people who are prediabetes or high risk of developing T2DM . Methods : The articles enrolled in the study will be retrieved from the online data bases between 2002 and the date the search es are executed . The search es will be repeated just before the final analyses and further relevant studies for inclusion . We will conduct a bibliographic search in data bases : Medline / PubMed , Scopus , Cochrane Library , EBSCO , and IndMED using keywords including prediabetes state , high risk for diabetes , metabolic syndrome , and yoga . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . There will be no language restrictions . Ethics and dissemination : The proposed study will be based on published studies and publicly available anonymized data without directly involving human participants and therefore requires neither formal human ethical review nor approval by a human research ethics committee . We published an outline of the protocol in the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in 2018 . We plan to disseminate the findings of this systematic review and meta- analysis through publication in a peer- review ed journal and presentation at relevant conference proceedings . In addition , we believe the results of the systematic review will have implication s for policy and practice . We will prepare policymaker summary using a vali date d format , disseminate through social media and email discussion groups . Review registration number : PROSPERO registration number CRD To investigate the relative effects of fructose and glucose on blood glucose , plasma insulin and incretin ( glucagon-like peptide-1 [ GLP-1 ] and gastric inhibitory peptide [ GIP ] ) concentrations , and acute food intake , 10 ( 6 men , 4 women ) patients with diet-controlled type 2 diabetes ( diabetic ) ( 44 to 71 years ) and 10 age and body mass index ( BMI ) -matched ( 6 men , 4 women ) nondiabetic , control subjects with varying degrees of glucose tolerance ( nondiabetic ) , were studied on 3 days . In r and om order , they drank equienergetic preloads of glucose ( 75 g ) ( GLUC ) , fructose ( 75 g ) ( FRUCT ) or vehicle ( 300 mL water with noncaloric flavoring [ VEH ] ) 3 hours before an ad libitum buffet lunch .  Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics ( FRUCT v GLUC : 7.5 + /- 0.3 v 10.8 + /- 0.4 mmol/L , P < .001 ) and nondiabetics ( FRUCT v GLUC : 5.9 + /- 0.2 v 7.2 + /- 0.3 mmol/L , P < .05 ) . Mean insulin concentrations were approximately 50 % higher after FRUCT in type 2 diabetics than in nondiabetics ( diabetics v nondiabetics : 23.1 + /- 0.7 v 15.1 + /- 1.3 microU/mL ; P < .0001 ) . Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics ( P > .05 ) . Glucose , but not FRUC , increased GIP concentrations , which were not different between type 2 diabetics and nondiabetics ( P > .05 ) . Food intake was suppressed 14 % by GLUC ( P < .05 v CONT ) and 14 % by FRUC ( P < .05 v CONT ) , with no difference between the amount of food consumed after GLUC and FRUC treatment in either type 2 diabetics or nondiabetics ( P > .05 ) . We have confirmed that oral fructose ingestion produces a lower postpr and ial blood glucose response than equienergetic glucose and demonstrated that ( 1 ) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics , not apparently due to greater plasma incretin concentrations and ( 2 ) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics . We conclude that on the basis of improved glycemic control , but not satiating efficiency , fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes 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 The aim of this study is to review recent data on dietary fiber ( DF ) and the glycemic index ( GI ) , with special focus on studies from the Nordic countries regarding cardiometabolic risk factors , type 2 diabetes , cardiovascular disease , cancer , and total mortality . In this study , recent guidelines and scientific background papers or up date s on older reports on DF and GI published between 2000 and 2011 from the US , EU , WHO , and the World Cancer Research Fund were review ed , as well as prospect i ve cohort and intervention studies carried out in the Nordic countries . All of the reports support the role for fiber-rich foods and DF as an important part of a healthy diet . All of the five identified Nordic papers found protective associations between high intake of DF and health outcomes ; lower risk of cardiovascular disease , type 2 diabetes , colorectal and breast cancer . None of the reports and few of the Nordic papers found clear evidence for the GI in prevention of risk factors or diseases in healthy population s , although association was found in sub-groups , e.g. overweight and obese individuals and suggestive for prevention of type 2 diabetes . It was concluded that DF is associated with decreased risk of different chronic diseases and metabolic conditions . There is not enough evidence that choosing foods with low GI will decrease the risk of chronic diseases in the population overall . However , there is suggestive evidence that ranking food based on their GI might be of use for overweight and obese individuals . Issues regarding methodology , validity and practicality of the GI remain to be clarified Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy BACKGROUND Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages ( SSBs )  , likely mainly because of an inadequate satiety response to liquid calories . However , SSBs have a high content of fructose , the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis . It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs . OBJECTIVE We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption . DESIGN We conducted 2 r and omized , controlled , double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose- , glucose- , or aspartame-sweetened beverage  ( study A ; n = 9 )  or a fructose- , glucose- , or high-fructose corn syrup (HFCS)-sweetened beverage  ( study B ; n = 24 ) for 8 d on overall energy intake . SSBs were provided at 25 % of estimated energy requirement , or an equivalent volume of the aspartame-sweetened beverage , and consumption was m and atory . All solid foods were provided at 125 % of estimated energy requirements and were consumed ad libitum . RESULTS In study A , ad libitum energy intake was 120 % ± 10 % , 117 % ± 12 % , and 102 % ± 15 % of estimated energy requirements when subjects consumed the fructose- , glucose- , and aspartame-sweetened beverages . Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase ( P < 0.003 for each ) , with no difference between the fructose and glucose phases ( P = 0.462 ) . In study B , total energy intake during the fructose , HFCS , and glucose phases was 116 % ± 14 % , 116 % ± 16 % , and 116 % ± 16 % of the subject 's estimated total energy requirements ( P = 0.880 ) . CONCLUSIONS In healthy adults , total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages . The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages . These trials were registered at clinical trials.gov as NCT00475475 and NCT01424306 We have studied whether the sucrose-induced reduction of insulin sensitivity and cellular insulin binding in normal man is related to the fructose or the glucose moiety . Seven young healthy subjects were fed their usual diets plus 1000 kcal extra glucose per day and eight young healthy subjects were fed their usual diets with addition of 1000 kcal extra fructose per day . The dietary regimens continued for 1 week . Before change of diet there were no statistically significant differences between body weight and fasting plasma concentrations of glucose , insulin , and ketone bodies in the two groups studied . High-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding ( P less than 0.05 ) and insulin sensitivity ( P less than 0.05 ) . The changes in insulin binding and insulin sensitivity correlated linearly ( r = 0.52 , P less than 0.01 ) . We conclude that fructose seems to be responsible for the impaired insulin binding and insulin sensitivity induced by sucrose 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 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 Previous epidemiological studies have shown that vigorous physical activity reduces the development of type 2 diabetes ( 1–3 ) . A recommendation from the Centers for Disease Control and Prevention reported that individuals should engage in ≥30 min of moderate-intensity physical activity , such as brisk walking , on most days of the week for health promotion and disease prevention ( 4 ) ; however , it is unclear whether mild physical activity ( i.e. , walking to walk ) reduces the risk for type 2 diabetes . In the present study , we examined the relationship between walking to work  and the development of type 2 diabetes during a 4-year observational period . The Kansai Healthcare Study is an ongoing cohort investigation design ed to clarify the risk factors for cardiometabolic diseases . Between April 2000 and March 2001 , 12,647 male employees of a company in the area of Kansai , Japan , who were aged 40–55 years at entry and considered to be involved in sedentary jobs were enrolled in this study . All employees aged ≥40 years underwent annual detailed medical check-ups . The protocol for this research was review ed by the Human Subjects Review Committee at Osaka City University . For current analysis , study participants consisted of 11,073 Japanese men aged 40–55 years at entry with a fasting plasma glucose ( FPG ) < 126 mg/dl and not taking oral hypoglycemic medication or insulin . A 4-year follow-up examination after baseline was conducted between April 2004 and March 2005 . We excluded 53 men because of death and 2,016 men because of 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 The effects of grain , fructose , and histidine on ruminal pH and fermentation products were studied in dairy cattle during an induced subacute acidosis protocol . Thirty Holstein heifers were r and omly allocated to 5 treatment groups : ( 1 ) control ( no grain ) ; ( 2 ) grain [ fed at a crushed triticale dry matter intake ( DMI ) of 1.2 % of body weight ( BW ) ] ; ( 3 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI ) ; ( 4 ) grain ( 1.2 % of BW DMI)+histidine ( 6 g/head ) ; and ( 5 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI)+histidine ( 6 g/head ) in a partial factorial arrangement . Heifers were fed 1 kg of grain daily with ad libitum access to ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before challenge day , on which heifers were fed 200 g of alfalfa hay and then the treatment diets immediately thereafter . Rumen sample s were collected 5 min after diet ingestion , 60 min later , and at 3 subsequent 50-min intervals . Grain decreased ruminal pH and increased ammonia , total volatile fatty acid ( VFA ) , acetate , butyrate , propionate , and valerate concentrations compared with controls . The addition of grain had no effect on ruminal D- and L-lactate concentrations . Fructose markedly decreased ruminal pH and markedly increased D- and L-lactate concentrations . Fructose increased total VFA and butyrate and decreased valerate concentrations . Although histidine did not have a marked effect on ruminal fermentation , increased concentrations of histamine were observed following feeding . This study demonstrates that the substitution of some grain for fructose can lower ruminal pH and increase VFA and lactate concentrations , warranting further investigation into the role of sugars on the risk of acidosis in dairy cattle AIMS In animals , intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation . In humans , functional brain magnetic resonance imaging ( fMRI ) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling , but no studies have compared the effects of glucose and fructose . We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process . METHODS Nine healthy , normal weight subjects underwent blood oxygenation level dependent ( BOLD ) fMRI measurements during either intravenous ( IV ) glucose ( 0.3 mg/kg ) , fructose ( 0.3 mg/kg ) or saline , administered over 2 min in a r and omized , double-blind , crossover study . Blood was sample d every 5 min during a baseline period and following infusion for 60 min in total for glucose , fructose , lactate and insulin levels . RESULTS No significant brain BOLD signal changes were detected in response to IV saline .  BOLD signal in the cortical control areas increased during glucose infusion ( p = 0.002 ) , corresponding with increased plasma glucose and insulin levels . In contrast , BOLD signal decreased in the cortical control areas during fructose infusion ( p = 0.006 ) , corresponding with increases of plasma fructose and lactate . Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus . CONCLUSION In normal weight humans , cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose . Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake 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 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 OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products ( AGEs ) , which are thought to impair glucose metabolism in type 2 diabetic patients . High intake of fructose might additionally affect endogenous formation of AGEs . This parallel intervention study investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals . RESEARCH DESIGN AND METHODS Seventy-four overweight women were r and omized to follow either a high- or low-AGE diet for 4 weeks , together with consumption of either fructose or glucose drinks .  Glucose and insulin concentrations — after fasting and 2 h after an oral glucose tolerance test — were measured before and after the intervention . Homeostasis model assessment of insulin resistance ( HOMA-IR ) and insulin sensitivity index were calculated . Dietary and urinary AGE concentrations were measured ( liquid chromatography t and em mass spectrometry ) to estimate AGE intake and excretion . RESULTS When adjusted for changes in anthropometric measures during the intervention , the low-AGE diet decreased urinary AGEs , fasting insulin concentrations , and HOMA-IR , compared with the high-AGE diet . Addition of fructose did not affect any outcomes . CONCLUSIONS Diets with high AGE content may increase the development of insulin resistance . AGEs can be reduced by modulation of cooking methods but is unaffected by moderate fructose intake The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P < 0.02 ) and the control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P < 0.05 ) . The mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P < 0.001 ) and the control diet ( from 10.3 + /- 0.3 mmol l-1 to 8.8 + /- 0.9 mmol l-1 , P < 0.01 ) . The HbA1 concentration improved ( P < 0.02 ) only during the fructose diet . Insulin sensitivity increased by 34 % ( P < 0.05 ) during the fructose diet , but remained unchanged during the control period . Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes OBJECTIVE High concentrations of fructose enhance postpr and ial lipemia following lipid loading whereas glucose exerts a negative or minimal effect . This study evaluated the effect of lower sweetener concentrations and the contribution of their sweetness level and palatability . METHODS At each of four test sessions , twelve male and ten female healthy adults ingested one of four milkshakes containing 108 g dairy cream alone or supplemented with 30 g fructose , 17.5 g glucose or 1 g aspartame .  Blood sample s were collected at baseline , two , four , six and eight hours after ingestion . Sensory discrimination tests were conducted after the last two sessions . RESULTS Fructose and glucose led to 37 % ( p = 0.03 ) and 59 % ( p = 0.08 ) rises in triacylglycerol area under the curve ( TG AUC ) when compared to the plain milkshake , respectively . Although the sweetened shakes were equisweet and were more palatable than the plain shake , the TG rise after the aspartame milkshake did not differ from the plain milkshake . CONCLUSIONS These data indicate that low levels of glucose and fructose consumed with lipid enhance postpr and ial lipemia . Sweetness and palatability did not account for the effect
Fructose consumption did not significantly affect fasting glucose or insulin .
A priori subgroup analyses showed no evidence of effect modification on any end point .
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 .
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 .